Anomeric reactivity-based one-pot oligosaccharide synthesis: A rapid route to oligosaccharide libraries

2410

J . Org. Chem. 2000, 65, 2410-2431

An om er ic Rea ctivity-Ba sed On e-P ot Oligosa cch a r id e Syn th esis: A

Ra p id Rou te to Oligosa cch a r id e Libr a r ies

Xin-Shan Ye and Chi-Huey Wong*

Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute,

10550 North Torrey Pines Road, La J olla, California 92037

Received October 6, 1999

The assembly of an oligosaccharide library has been achieved in a practical and efficient manner

employing a one-pot sequential approach. With the help of the anomeric reactivity values of

thioglycosides, using a thioglycoside (mono- or disaccharide) with one free hydroxyl group as acceptor

and donor coupled with another fully protected thioglycoside, a di- or trisaccharide is selectively

formed without self-condensation and subsequently reacted in situ with an anomerically inactive

glycoside (mono- or disaccharide) to form a tri- or tetrasaccharide in high overall yield. The approach

enables the rapid assembly of 33 linear or branched fully protected oligosaccharides using designed

building blocks. These fully protected oligosaccharides have been partially or completely deprotected

to create 29 more structures to further increase the diversity of the library.

In tr od u ction

Recently, a new chemoselective glycosylation strategy,

“the one-pot sequential glycosylation”,¹²has received

considerable interest as it provides a rapid route to

oligosaccharides. This strategy is, however, not generally

applicable due to the lack of precise reactivity values of

useful glycosyl donors and acceptors. To tackle this

problem, the relative reactivity values of a number of

glycosylation reagents have been established recently,¹³

and a computer program has been developed to guide the

Carbohydrates contain an evolutionary potential of

information content several orders of magnitude higher

in a short sequence than any other biological oligomer

due to their monomers capable of more than one linkage

position, anomerity, and branching.¹For example, the

number of all possible linear and branched isomers of a

hexasaccharide was calculated and found to be >1.05 ×

10¹². It has been well-documented that the structural

diversity of sugar oligomers leads to their involvement

in many key inter- and intracellular events.^2,3Cells,

bacteria, viruses, and toxins often use cell-surface car-

bohydrates as points of attachment.⁴These and other

important discoveries in molecular glycobiology have

stimulated intense research in oligosaccharides, focusing

on both their synthesis and structure-function relation-

ship study.

(7) Kanie, O.; Barresi, F.; Ding, Y.; Labbe, J .; Otter, A.; Forsberg,

L. S.; Ernst, B.; Hindsgaul, O. Angew. Chem., Int. Ed. Engl. 1995, 34,

2720-2722. Ding, Y.; Kanie, O.; Labbe, J .; Palcic, M. M.; Ernst, B.;

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1996, 4, 683-692.

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1997, 26, 407-415.

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110, 2662-2663. Fraser-Reid, B.; Udodong, U. E.; Wu, Z.; Ottoson, H.;

Merritt, J . R.; Rao, C. S.; Roberts, C.; Madsen, R. Synlett 1992, 927-

942. Veeneman, G. H.; van Boom, J . H. Tetrahedron Lett. 1990, 31,

275-278. Zuurmond, H. M.; van der Laan, S. C.; van der Marel, G.

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34, 8523-8526.

Unlike peptide and nucleotide synthesis, oligosaccha-

ride synthesis is not a facile process. It is complicated

by the issues of anomeric stereochemistry and protecting

group manipulation. Therefore, the need for rapid access

to oligosaccharides for the better understanding of bio-

logical processes is still a formidable challenge. Major

advances⁵have been made in this field using strategies

such as glycal assembly,⁶random-glycosylation,⁷latent-

active glycosylation,⁸enzyme-assisted synthesis,⁹armed/

disarmed glycosylation,¹⁰and solid-phase approach.¹¹

(11) Liang, R.; Yan, L.; Loebach, J .; Ge, M.; Uozumi, Y.; Sekanina,

K.; Horan, N.; Gildersleeve, J .; Thompson, C.; Smith, A.; Biswas, K.;

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1581. (b) Yamada, H.; Harada, T.; Takahashi, T. J . Am. Chem. Soc.

1994, 116, 7919-7920. Yamada, H.; Harada, T.; Miyazaki, H.; Taka-

hashi, T. Tetrahedron Lett. 1994, 35, 3979-3982. Yamada, H.; Kato,

T.; Takahashi, T. Tetrahedron Lett. 1999, 40, 4581-4584. (c) Ley, S.

V.; Priepke, H. W. M. Angew. Chem., Int. Engl. 1994, 33, 2292-2294.

Grice, P.; Ley, S. V.; Pietruszka, J .; Prieke, H. W. M.; Walther, E. P.

E. Synlett 1995, 781-784. Grice, P.; Ley, S. V.; Pietruszka, J .; Osborn,

H. M. I.; Priepke, H. W. M.; Warriner, S. L. Chem. Eur. J . 1997, 3,

431-440. Cheung, M.-K.; Douglas, N. L.; Hinzen, B.; Ley, S. V.;

Pannecoucke, X. Synlett 1997, 257-260. Green, L.; Hinzen, B.; Ince,

S. J .; Langer, P.; Ley, S. V.; Warriner, S. L. Synlett 1998, 440-442.

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12074. (e) Chenault, H. K.; Castro, A. Tetrahedron Lett. 1994, 35,

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Achiha, T.; Kiyoi, T.; Kondo, H. J . Org. Chem. 1997, 62, 6876-6881.

(g) Geurtsen, R.; Holmes, D. S.; Boons, G.-J . J . Org. Chem. 1997, 62,

8145-8154. Boons, G.-J .; Zhu, T. Synlett 1997, 809-811. (h) Lu, S.-

F.; O’yang, Q.; Guo, Z.-W.; Yu, B.; Hui, Y.-Z. J . Org. Chem. 1997, 62,

8400-8405.

(1) Laine, R. A. Glycobiology 1994, 4, 759-767. Laine, R. A. Pure

Appl. Chem. 1997, 69, 1867-1873.

(2) Varki, A. Glycobiology 1993, 3, 97-130. Sears, P.; Wong, C.-H.

Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 12086-12093.

(3) Sharon, N.; Lis, H. Sci. Am. 1993, 268, 82-89.

(4) Montreuil, J . Adv. Carbohydr. Chem. Biochem. 1980, 37, 157-

223. Kobata, A. In Biology of Carbohydrates; Ginsberg, V., Ed.; Wiley:

New York, 1984. Glycoproteins; Gottschalk, A., Ed.; Elsevier: Amster-

dam, 1972. Lis, H.; Sharon, N. Eur. J . Biochem. 1993, 218, 1-27.

Karlsson, K.-A. Trends Pharmacol. Sci. 1991, 12, 265. Rademacher,

T. W.; Parekh, R. B.; Dwek, R. A. Annu. Rev. Biochem. 1988, 57, 785-

838. Feizi, T. Nature (London) 1985, 314, 53-57.

(5) For recent reviews, see: Arya, P.; Ben, R. N. Angew. Chem., Int.

Ed. Engl. 1997, 36, 1280-1282. Paulsen, H. Angew. Chem., Int. Ed.

Engl. 1995, 34, 1432-1434. Preparative Carbohydrate Chemistry;

Hanessian, S., Ed.; Marcel Dekker, Inc.: New York, 1997.

(6) Danishefsky, S. J .; Bilodeau, M. T. Angew. Chem., Int. Ed. Engl.

1996, 35, 1380-1419.

Published on Web 03/28/2000

One-Pot Oligosaccharide Synthesis

J . Org. Chem., Vol. 65, No. 8, 2000 2411

Sch em e 1. Str a tegy for On e-P ot Assem bly of Lin ea r a n d Br a n ch ed Oligosa cch a r id es

selection of building blocks for sequential one-pot oligo-

saccharide synthesis.^13bOn the other hand, an orthogonal

protection-deprotection strategy for the synthesis of a

highly branched oligosaccharide library has also been

developed.¹⁴With the aid of the anomeric relative reac-

tivity values, we report here a rapid and practical

assembly of a small tri- and tetrasaccharide library based

on the combination of orthogonal protection-deprotection

and one-pot sequential glycosylation strategies using

thioglycosides¹⁵as glycosylation reagents.

(13) (a) Douglas, N. L.; Ley, S. V.; Lu¨cking, U.; Warriner, S. L. J .

Chem. Soc., Perkin Trans. 1 1998, 51-65. (b) Zhang, Z.; Ollmann, I.

R.; Ye, X.-S.; Wischnat, R.; Baasov, T.; Wong, C.-H. J . Am. Chem. Soc.

1999, 121, 734-753.

(14) Wong, C.-H.; Ye, X.-S.; Zhang, Z. J . Am. Chem. Soc. 1998, 120,

7137-7138.

(15) Fu¨gedi, P.; Garegg, P. J . Carbohydr. Res. 1986, 149, C9-C12.

2412 J . Org. Chem., Vol. 65, No. 8, 2000

Ye and Wong

Sch em e 2

Sch em e 3^a

Resu lts a n d Discu ssion

The principle of the one-pot sequential glycosylation

is illustrated in Scheme 1. If the difference in the

reactivity between glycosyl donor A (X ) leaving group)

and acceptor as well as donor B is large enough to be

distinguished by a promotor, the donor A can be selec-

tively activated to react with B to give the disaccharide

intermediate, which upon activation and coupling with

the glycosyl acceptor C (the third component) will provide

the trisaccharide D in one pot without contamination of

byproducts derived from self-condensation of B and other

undesirable coupling. Here, B functions as both an

acceptor for the first glycosylation and a donor for the

second glycosylation (we call B acceptor-donor). In this

way, two glycosidic linkages are sequentially constructed

in a one-pot reaction. If B is a disaccharide acceptor-

donor, a branched tetrasaccharide will be formed. Simi-

larly, if a disaccharide acceptor C is used, a tetrasaccha-

ride will also be produced. We envisaged that this

strategy would provide a powerful tool for the assembly

of oligosaccharide libraries. For instance, if six donors

(A^1-6), seven acceptor-donors (B^1-7), and four acceptors

(C^1-4) are employed, 672 (6 × 7 × 4 × 2 × 2 ) 672)

oligosaccharides (A^1-6B^1-7C^1-4) (including anomeric iso-

mers) will be formed in principle, and a computer

program^13bcan be used as a guide for selection of

appropriate building blocks for the assembly of a large

number of oligosaccharides (Scheme 1). To verify the

proposed strategy, a relatively small library of 33 oligo-

saccharides has been prepared.

a

Key: (a) N,N-diisopropylethylamine, MeOH; then phthalic

anhydride; (b) Ac₂O, pyridine, DMAP, 52%; (c) methyl 6-hydroxy-

hexanate, BF₃‚OEt₂, CH₂Cl₂, 73%; (d) NaOMe, MeOH, 99%; (e)

anisaldehyde dimethyl acetal, 10-camphorsulfonic acid, MeCN,

81%; (f) BnBr, NaH, DMF, 54%; (g) NaCNBH₃, CF₃CO₂H, DMF,

90%; (h) NaCNBH₃, Me₃SiCl, MeCN, 51%.

Sch em e 4

To realize this goal and enhance the diversity of the

library, suitably protected building blocks have to be

designed carefully. Our previous paper¹⁴indicated that

the four protecting groupsschloroacetyl (ClAc), p-meth-

oxybenzyl (PMB), levulinyl (Lev), and tert-butyldiphen-

ylsilyl (TBDPS)son a galactoside can be selectively

removed. The same result was obtained from thiogalac-

todide 1 as shown in Scheme 2. Selective deprotection of

the PMB group in 1 using trifluoroacetic acid (TFA) gave

acceptor-donor 2 in high yield (99%).

Synthesis of glucosamine acceptors 6a -c was per-

formed as depicted in Scheme 3. Treatment of glucos-

amine hydrogen chloride (3) with phthalic anhydride and

subsequent O-acetylation afforded 4. Glycosylation of 4

and methyl 6-hydroxyhexanate followed by O-deacety-

lation gave 5 (72%). 4,6-O-p-Methoxybenzylidenation of

5 provided acceptor 6a with the 3-hydroxyl group ex-

posed. Benzylation of 6a gave saccharide 7 in 54% yield.

Regioselective reductive ring-opening¹⁶of 4,6-O-p-meth-

oxybenzylidene acetal of 7 produced acceptor 6b and 6c

with the 4- and 6-hydroxyl groups exposed, respectively.

Our initial one-pot trisaccharide assembly was per-

formed with thioglycoside donor 1a (RRV ) 1.7 × 10⁴),¹⁴

acceptor-donor 2 (RRV ) 57.0), and glycosyl acceptor

6a . As illustrated in Scheme 4, glycosylation of 1a and 2

gave the intermediate disaccharide 8 in R-glycosidic

linkage, which was then coupled with acceptor 6a to

provide 9 in high yield (80%). Both two glycosylation

steps were activated by N-iodosuccinimide and triflic acid

(NIS-TfOH).¹⁷Unfortunately, compound 9 is not our

desired trisaccharide, but an ortho ester. When promotor

(dimethylthio)methylsulfonium triflate (DMTST)^14,15was

employed instead of NIS-TfOH, the same product was

isolated. The ortho ester was evident from the coupling

constant of the anomeric proton at δ 5.48 ppm (J ) 5.5

Hz).

To avoid the formation of ortho esters, the chloroacetyl

protecting group of 2 was simply changed to the benzoyl

(17) Konradsson, P.; Udodong, U. E.; Fraser-Reid, B. Tetrahedron

Lett. 1990, 31, 4313-4316. Konradsson, P.; Mootoo, D. R.; McDevitt,

R. E.; Fraser-Reid, B. J . Chem. Soc., Chem. Commun. 1990, 270-272.

Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J . H. Tetrahedron

Lett. 1990, 31, 1331-1334.

(16) J ohansson, R.; Samuelsson, B. J . Chem. Soc., Perkin Trans. 1

1984, 2371-2374.

One-Pot Oligosaccharide Synthesis

J . Org. Chem., Vol. 65, No. 8, 2000 2413

Sch em e 5^a

Sch em e 7

Sch em e 8.^aSyn th esis of Disa cch a r id e

Accep tor -Don or s 2e-g

a

Key: (a) NaHCO₃, MeOH/H₂O, 100%; (b) BzCl, pyridine, 100%;

(c) TFA, CH₂Cl₂, 58%; (d) hydrazine, AcOH, 92%; (e) HF-pyridine,

100%.

Sch em e 6

a

Key: (a) NIS, TfOH, molecular sieves, CH₂Cl₂; (b) TFA,

CH₂Cl₂; (c) HF-pyridine.

2b, 2c, and 2d with one free hydroxyl group at the 3, 4,

and 6-positions, respectively.

After the benzoyl group was introduced instead of the

chloroacetyl group, we continued to perform the one-pot

trisaccharide assembly. The highly reactive thioglycoside

donor 1c (RRV ) 7.2 × 10⁴), acceptor-donor 2b (RRV )

142.9), and acceptor 6a were chosen. As shown in Scheme

6, 1c and 2b were coupled in the presence of N-

iodosuccinimide and a catalytic amount of triflic acid to

generate the intermediate disaccharide 11 in R-1,3-

glycosidic linkage, which was activated by the same

promotor (NIS-TfOH) followed by addition of the third

coupling component 6a to the reaction mixture to give

the trisaccharide 12 in 74% overall isolated yield. This

constitutes an average of over 85% conversion per gly-

cosylation. The reaction process was monitored by TLC.

Because excess amounts of 6a (3 equiv) and 1c (1.5 equiv)

protecting group. The transformation of thioglycoside 1

to acceptor-donors 2a -d is outlined in Scheme 5.

Selective removal of chloroacetyl group on saccharide 1

with NaHCO₃afforded the 2-hydroxyl group exposed

acceptor-donor 2a in quantitative yield. Benzoylation of

2a gave fully protected saccharide 10. Selective depro-

tection of 10 with trifluoroacetic acid, hydrazine, and

hydrogen fluoride-pyridine provided acceptor-donors

2414 J . Org. Chem., Vol. 65, No. 8, 2000

Sch em e 9. Bu ild in g Block s for th e Assem bly of Oligosa cch a r id es^{a ,b}

Ye and Wong

a

PMB ) p-methoxybenzyl, TBDPS ) tert-butyldiphenylsilyl, Lev ) Levulinyl, NPhth ) N-Phthaloyl, R ) (CH₂)₅CO₂Me. ^bThe relative

reactivity value (RRV) is shown in parentheses.

were used, a 1,3-component coupling product disaccha-

ride 13 as an anomeric mixture (R/â ) 9:2 from NMR

analysis, 19%) and a recovery of 6a were also isolated.

We also tried to assemble a trisaccharide with mannose

thioglycoside 14, benzoyl protected acceptor-donor 2b,

and acceptor 6a under the same conditions as mentioned

above. As shown in Scheme 7, no disaccharide or trisac-

charide was detected. Interestingly, the starting material

2b was converted to 15 in 87% isolated yield, and the

other two reactants 14 and 6a were recovered. This result

perhaps can be explained by the relative reactivity

values.^13bDonor 14 (RRV ) 1.0) is less reactive than 2b

(RRV ) 142.9), so 2b should be activated more easily

than 14. Actually, donor 14 is too unreactive to be

activated by NIS-TfOH for glycosylation.

removal of PMB group in 16 with TFA furnished 2e in

61% yield. In a similar way, disaccharides 2f and 2g were

obtained in 72% and 71% overall yield, respectively.

Thus, a galactose moiety with a free hydroxyl group at

the 2-, 3-, 4-, or 6-position (2a -d ) and three orthogonally

protected disaccharide thioglycosides with one hydroxyl

group exposed (2e-g) were prepared as the central part

(acceptor-donor B) to build oligosaccharides. For the

preparation of acceptor-donors 2a -g, the key feature

is the use of an orthogonal protection-deprotection

strategy. Starting from a monosaccharide core, a di-, tri-,

or tetrasaccharide carrying one free hydroxyl group can

be made in a combinatorial fashion in principle. These

structures can then be subjected to the one-pot assembly

of oligosaccharides.

To increase the diversity of acceptor-donors, some

disaccharide acceptor-donors 2e-g were prepared

(Scheme 8). The coupling reaction of 1c and 2c in the

presence of NIS-TfOH afforded disaccharide 16 in 74%

yield with complete stereochemistry control. Selective

In our method for the one-pot glycosylation, five

thioglycoside donors 1a -e (donor A) were employed.

Similarly, for acceptor C, we used three differently

protected glucosamines 6a -c and one disaccharide 6d

as acceptors for the construction of oligosaccharides.

One-Pot Oligosaccharide Synthesis

J . Org. Chem., Vol. 65, No. 8, 2000 2415

Sch em e 10

ate in the presence of boron trifluoride etherate in CH₂-

Cl₂(0 °C to rt) to afford 23 (56%). The stereochemical

1

assignment was confirmed by H NMR, where the J _1,2

value of 7.9 Hz for H-1 indicated the â-D-configuration

for the side chain. Deacetylation of 23 followed by 4,6-

O-benzylidene protection produced saccharide 24 (87%,

two steps). Interestingly, when 24 was treated with

chloroacetyl chloride in pyridine-Et₃N-CH₂Cl₂at -20

°C, the desired 3-chloroacetyl saccharide 25 was isolated

as the major product (50%), but the 2,3-dichloroacetyl

saccharide 26 was also isolated (25%). With the suitably

protected galactoside 25 in hand, the glycosylation with

thioglycoside 1c promoted by (dimethylthio)methylsul-

fonium triflate in CH₂Cl₂(0 °C to rt) was achieved to

afford disaccharide 27 (83%). The R-configuration of the

newly formed glycosidic linkage was evident from the

coupling constant of the anomeric proton at δ 5.23 ppm

(J ) 3.5 Hz). Deprotection of chloroacetyl group on

disaccharide 27 finally gave 6d (99%).

With all these building blocks in hand, under the

guidance of the relative reactivity values, a one-pot

approach to oligosaccharide libraries was attempted. In

a representative synthesis of the branched tetrasaccha-

ride 28, DMTST was used as a promotor for the first-

step coupling between donor 1b and disaccharide accep-

tor-donor 2e. The reaction proceeded smoothly under

these conditions, and the product, without the isolation,

was further treated with acceptor 6b in situ in the

presence of NIS-TfOH to afford 28 in 51% yield (Scheme

12). In this case, NIS-TfOH is too reactive to be used as

an effective reagent for the coupling of 1b (RRV ) 2656)

and 2e (RRV ) 268.6). In fact, we found that the reaction

proceeded with very fast consumption of 1b to give

exclusively the succinimide glucoside when NIS-TfOH

was used as an initial promotor. We assume that the

elevated reactivity of donor 1b coupled with high steric

hindrance of the secondary hydroxyl group in 2e leads

to a very efficient competition of succinimide to provide

the byproduct. For the assembly of tetrasaccharides 29

and 30, we found that DMTST is an efficient coupling

reagent for both the first-step and the second-step

glycosylation. The highly reactive donor 1c (RRV ) 7.2

× 10⁴) was coupled with acceptor-donor 2b (RRV )

142.9) followed by addition of acceptor 6d in the presence

of DMTST to afford separatable tetrasaccharides 29 and

30 in 30% and 24% isolated yield, respectively. It seems

that NIS-TfOH is generally a more efficient promotor

than DMTST. If a highly reactive donor such as 1c was

coupled with a sterically hindranced acceptor, DMTST

should be employed instead of the NIS-TfOH system to

avoid the formation of a succinimide derivative. In this

way, a small fully protected oligosaccharide library (33

tri- or tetrasaccharides) in which the central galactose

moiety can be linked at any position was assembled, and

the results are summarized in Chart 1. The linear and

branched structures are biologically relevent. Most of the

constructed oligosaccharides were isolated in pure isomer

in 50-80 mg, and all these structures were characterized

Sch em e 11

Building blocks for the assembly of oligosaccharides are

listed in Scheme 9.

The preparation of some monosaccharide building

blocks is summarized in Scheme 10. Thus, manipulation

of galactosamine derivative 19¹⁸with p-thiocresol in the

presence of boron trifluoride etherate gave thioglycoside

20 (68% yield). Treatment of 20 with sodium methoxide

followed by benzylation gave chromatographically sepa-

ratable anomeric isomers 1d and 21 (95% yield). Simi-

larly, mannose derivative 14 was converted to thiogly-

coside 1e in 76% yield.

1

by their H and ¹³C NMR and further confirmed by high-

resolution mass analysis. People may think the separa-

tion of the products could be a tough task. According to

our experience, the isolation of products is not very

difficult. Actually, all the separation work was ac-

complished by a routine column chromatography tech-

nique. Thus, good separation of unreacted acceptor, major

side-product 1,3-component coupling product, and desired

The synthesis of disaccharide acceptor 6d was shown

in Scheme 11. The synthesis was started from the

commerically available galactose pentaacetate (22), which

was directly glycosylated with methyl 6-hydroxy hexan-

(18) Alper, P. B.; Hung, S.-C.; Wong, C.-H. Tetrahedron Lett. 1996,

37, 6029-6032.

2416 J . Org. Chem., Vol. 65, No. 8, 2000

Ye and Wong

One-Pot Oligosaccharide Synthesis

J . Org. Chem., Vol. 65, No. 8, 2000 2417

Sch em e 12

Sch em e 13

catalytic hydrogenolysis over 10% Pd-C to give trisac-

charide 62 (35% yield from 32). The final products 61

and 62 were purified by C-18 reversed-phase column

chromatography. In this manner, most of fully protected

oligosaccharides assembled from one-pot access were

partially deprotected. Their structures (29 partially or

fully deprotected oligosaccharides) are listed in Chart 2.

1

All structures were identified by their H NMR, ¹³C NMR,

and mass spectral analysis.

Con clu sion

The strategy disclosed here for the construction of

saccharide libraries is very efficient, and only a small

number of building blocks is employed to generate a

relatively large number of oligosaccharides. To our

knowledge, this is the first oligosaccharide library created

by one-pot assembly. Furthermore, the described prin-

ciple points out a possible route to the assembly of more

complex and biologically significant oligosaccharides in

a rapid fashion if combined with the use of the computer

program Optimer^13band possibly forms the basis for

automated carbohydrate synthesis. As interest in the

database increases, the computer program for the selec-

tion of building blocks will receive more interest. Work

is in progress to enlarge the size of the building blocks

for preparation of a larger library and to screen for

binders to certain proteins and nucleic acids.

oligosaccharide (usually in form of a pure isomer, in some

case in form of an anomeric mixture) was achieved (see

the Experimental Section).These protected oligosaccha-

rides can be partially and fully deprotected to generate

a larger library. From some point of view, an oligosac-

charide that retains one or two hydrophobic groups in it

may probably have stronger binding affinity due to the

hydrophobic interaction. As examplified in Scheme 13,

trisaccharide 32 was successively treated with hydrogen

fluoride-pyridine, hydrazine, and hydrogen over Pd on

charcoal to afford the partially deprotected saccharide 61

(74% yield, three steps). A complete deprotection of

compound 32 was accomplished as follows: the tert-

butyldiphenylsilyl and p-methoxybenzylidine function-

alities were removed by hydrogen fluoride-pyridine, the

levulinyl functionality was removed by hydrazine, the

phthalimido functionality was converted into an NHAc

moiety by treatment with hydrazine acetate and reacety-

lation with acetic anhydride in pyridine, the benzoyl

functionality was removed by methanolic sodium meth-

oxide, and the benzyl protecting groups were cleaved by

Exp er im en ta l Section

Gen er a l Meth od s. Tetrahydrofuran (THF), toluene, and

diethyl ether (Et₂O) were distilled over sodium/benzophenone,

methylene chloride (CH₂Cl₂), and acetonitrile (CH₃CN) over

calcium hydride. Reagents of commercial quality were pur-

chased and used without further purification unless otherwise

stated. Compounds 1a -c, 2a -g, 6a ,b, 7, and 14 were prepared

Ch a r t 2. P a r tia lly a n d F u lly Dep r otected Oligosa cch a r id es

One-Pot Oligosaccharide Synthesis

J . Org. Chem., Vol. 65, No. 8, 2000 2419

previously.^13,14All reactions were carried out under an argon

atmosphere with dry, freshly distilled solvents under anhy-

drous conditions, unless otherwise noted.

(500 MHz, CDCl₃) δ 7.67-7.84 (m, 2H), 7.56 (t, J ) 6.5 Hz,

4H), 7.22-7.42 (m, 30H), 6.89 (d, J ) 9.0 Hz, 2H), 5.50 (s,

1H), 5.48 (d, J ) 5.5 Hz, 1H), 5.43 (d, J ) 2.5 Hz, 1H), 5.20 (d,

J ) 8.5 Hz, 1H), 5.16 (d, J ) 3.0 Hz, 1H), 4.90 (d, J ) 11.0 Hz,

1H), 4.76-4.82 (ABq, 2H), 4.69 (t, J ) 9.5 Hz, 1H), 4.62-4.68

(ABq, 2H), 4.56 (d, J ) 11.0 Hz, 1H), 4.43 (d, J ) 11.5 Hz,

1H), 4.37 (d, J ) 12.0 Hz, 1H), 4.35 (dd, J ) 11.0, 4.5 Hz, 1H),

4.20 (dd, J ) 10.0, 9.0 Hz, 1H), 3.99-4.13 (m, 4H), 3.91 (dd, J

) 7.0, 3.0 Hz, 1H), 3.76-3.82 (m, 3H), 3.64 (s, 3H), 3.59 (s,

3H), 3.37-3.67 (m, 10H), 2.06-2.38 (m, 4H), 1.99 (s, 3H),

1.93-2.01 (m, 2H), 1.30-1.42 (m, 4H), 1.01-1.11 (m, 2H), 0.98

(s, 9H); ¹³C NMR (125 MHz, CDCl₃) δ 205.9, 173.8, 170.9,

160.0, 139.0, 138.8, 138.7, 137.7, 135.6, 135.5, 134.4, 133.2,

133.1, 129.7, 128.4, 128.3, 128.2, 128.1, 128.1, 128.0, 127.8,

127.7, 127.7, 127.6, 127.4, 127.4, 123.5, 118.3, 113.7, 101.5,

98.8, 98.6, 93.1, 80.74, 78.89, 76.07, 75.44, 74.92, 74.78, 73.64,

73.19, 72.57, 72.12, 72.06, 70.22, 69.66, 69.12, 68.67, 68.34,

66.28, 63.19, 61.42, 55.91, 55.12, 51.32, 45.79, 37.85, 33.70,

29.58, 28.98, 27.72, 26.77, 25.32, 24.39, 19.07; HRMS (M +

Cs) calcd for C₉₂H₁₀₂O₂₃NSiClCs 1784.5355, found 1784.5486.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

[2-O-b e n zoyl-3-O-(2,3,4-t r i-O-b e n zyl-r-^L-fu cop yr a n os-

yl)-4-O-levu lin yl-6-O-ter t-bu tyld ip h en ylsilyl-â-^D-ga la cto-

pyr an osyl]-4,6-O-p-m eth oxyben zyliden e-â-^D-glu copyr an o-

sid e (12). To a solution of 1c (58.0 mg, 0.107 mmol) and 2b

(52.0 mg, 0.072 mmol) in CH₂Cl₂(5 mL) was added 4 Å

molecular sieves (600 mg), and the mixture was stirred for 30

min at room temperature and then cooled to - 20 °C. NIS (25.0

mg, 0.107 mmol) and TfOH (35 µL, 0.3 M etheral solution)

were added to the mixture, and this mixture was stirred for

15 min at - 20 °C. To the reaction mixture were added a

solution of 6a (119.0 mg, 0.215 mmol) in CH₂Cl₂(3 mL), NIS

(25.0 mg, 0.107 mmol), and TfOH (45 µL, 0.3 M etheral

solution). The reaction mixture was stirred for 30 min at -20

°C. The course of the reaction was monitored by TLC. Et₃N

(1.5 mL) was then added to the mixture. The precipitate was

filtered off, and the filtrate was successively washed with

saturated aqueous Na₂S₂O₃, NaHCO₃, and brine. The organic

layer was dried over Na₂SO₄and concentrated. The residue

was purified by column chromatography on silica gel (hexanes/

EtOAc 3:1 to 2:1) to give 12 (83.0 mg, 74%) as a thick oil and

the 1,3-component coupling product 13 (19.8 mg, 19%) as a

thick oil that was recently deprotected to form compound 80

(see the preparation of saccharide 80). For compound 12: ¹H

NMR (500 MHz, CDCl₃) δ 7.55 (d, J ) 7.0 Hz, 2H), 7.48 (d, J

) 7.0 Hz, 2H), 7.04-7.44 (m, 30H), 6.79-6.82 (m, 4H), 5.45

(d, J ) 3.0 Hz, 1H), 5.37 (s, 1H), 5.29 (dd, J ) 8.0, 10.0 Hz,

1H), 5.00 (d, J ) 8.5 Hz, 1H), 4.91 (d, J ) 2.5 Hz, 1H), 4.81 (d,

J ) 11.5 Hz, 1H), 4.70 (d, J ) 8.5 Hz, 1H), 4.68 (dd, J ) 9.0,

10.0 Hz, 1H), 4.56-4.63 (ABq, J ) 12.0 Hz, 2H), 4.53 (d, J )

11.5 Hz, 1H), 4.28 (dd, J ) 4.5, 10.5 Hz, 1H), 4.22 (dd, J )

8.5, 10.0 Hz, 1H), 4.17 (q, J ) 6.5 Hz, 1H), 4.02 (dd, J ) 3.5,

10.5 Hz, 1H), 3.87-3.94 (ABq, J ) 12.0 Hz, 2H), 3.72-3.80

(m, 3H), 3.71(s, 3H), 3.68-3.70 (m, 1H), 3.66 (s, 3H), 3.59-

3.64 (m, 2H), 3.58 (s, 3H), 3.53 (q, J ) 4.5 Hz, 1H), 3.27 (dt, J

) 9.5, 6.5 Hz, 1H), 2.57 (t, J ) 7.0 Hz, 2H), 2.31-2.48 (m,

2H), 1.98 (s, 3H), 1.82-1.92 (m, 2H), 1.19-1.34 (m, 4H), 1.10

(d, J ) 6.5 Hz, 3H), 0.99 (s, 9H), 0.89-0.97 (m, 2H); ¹³C NMR

(125 MHz, CDCl₃) δ 206.1, 173.8, 171.8, 163.9, 160.0, 138.8,

138.4, 138.3, 135.8, 135.5, 133.6, 133.0, 132.5, 132.5, 129.9,

129.8, 129.6, 129.3, 129.2, 128.4, 128.2, 128.1, 128.1, 127.7,

127.7, 127.6, 127.5, 127.3, 127.2, 127.2, 127.1, 127.1, 126.8,

113.6, 100.8, 100.5, 98.6, 98.5, 80.95, 78.49, 77.41, 75.43, 74.66,

73.58, 73.07, 72.82, 72.59, 71.59, 69.39, 68.77, 68.47, 67.13,

66.28, 64.30, 60.58, 55.29, 55.12, 51.32, 38.29, 33.56, 29.57,

28.77, 28.36, 26.72, 25.13, 24.20, 18.91, 16.42; HRMS (M +

Cs) calcd for C₉₀H₉₉O₂₂NSiCs 1706.5482, found 1706.5604.

Com p ou n d 15. To a solution of 14 (46.9 mg, 0.1033 mmol)

and 2b (50.0 mg, 0.06887 mmol) in CH₂Cl₂(5 mL) was added

4 Å molecular sieves (600 mg), and the mixture was stirred

for 30 min at room temperature and then cooled to -20 °C.

NIS (24.5 mg, 0.1033 mmol) and TfOH (50 µL, 0.3 M etheral

solution) were added to the mixture, and this mixture was

stirred for 40 min at -20 °C. To the reaction mixture was

added a solution of 6a (114.7 mg, 0.2066 mmol) in CH₂Cl₂(3

p-Met h ylp h en yl 2-O-Ch lor oa cet yl-4-O-levu lin yl-6-O-

ter t-bu tyld ip h en ylsilyl-1-th io-â-^D-ga la ctop yr a n osid e (2).

To a stirred solution of p-methylphenyl 2-O-chloroacetyl-3-O-

p-methoxybenzyl-4-O-levulinyl-6-O-tert-butyldiphenylsilyl-1-

thio-â-^D-galactopyranoside¹⁴(104 mg, 0.127 mmol) in CH₂Cl₂

(8 mL) was added trifluoroacetic acid (1.5 mL) at - 20 °C. After

the mixture was stirred for 20 min at this temperature,

methanol (2 mL) and CH₂Cl₂(20 mL) were then added to the

reaction mixture, and the mixture was washed with saturated

NaHCO₃and brine and then dried over Na₂SO₄. After removal

of the solvent, the residue was purified by chromatography

on a silica gel column (hexanes-EtOAc 2.5:1) to yield 2 (87.9

mg, 99%) as a syrup: ¹H NMR (400 MHz, CDCl₃) δ 7.62-7.66

(m, 4H), 7.35-7.45 (m, 8H), 7.06 (d, J ) 7.9 Hz, 2H), 5.54 (d,

J ) 3.1 Hz, 1H), 4.94 (t, J ) 9.8 Hz, 1H), 4.60 (d, J ) 10.0 Hz,

1H), 4.16 (s, 1H), 4.15 (s, 1H), 3.83 (dd, J ) 9.6, 3.2 Hz, 1H),

3.71-3.78 (m, 2H), 3.64 (dd, J ) 9.0, 5.7 Hz, 1H), 2.63-2.79

(m, 2H), 2.35-2.50 (m, 2H), 2.32 (s, 3H), 2.13 (s, 3H), 1.04 (s,

9H); ¹³C NMR (100 MHz, CDCl₃) δ 208.33, 171.96, 166.54,

138.20, 135.58, 135.55, 133.09, 129.80, 129.76, 129.60, 127.71,

86.30, 77.71, 72.54, 72.34, 70.30, 61.77, 40.84, 38.38, 29.61,

28.14, 26.69, 21.08, 19.05; HRMS (M + Na) calcd for C₃₆H₄₃O₈-

SSiClNa 721.2034, found 721.2005.

5-Meth oxyca r bon ylp en tyl 3-O-Ben zyl-4-O-p-m eth oxy-

ben zyl-2-d eoxy-2-p h th a lim id o-â-^D-glu cop yr a n osid e (6c).

To a mixture of 5-methoxycarbonylpentyl 2-deoxy-2-phthal-

imido-3-O-benzyl-4,6-O-p-methoxybenzylidene-â-^D-glucopyranoside

(7) (2.90 g, 4.5 mmol), NaCNBH₃(1.80 g, 27.0 mmol), and 3 Å

molecular sieves (6.0 g, powder) in CH₃CN (anhydrous, 80 mL),

was added dropwise a solution of Me₃SiCl (2.99 g, 27.0 mmol)

in CH₃CN (27 mL) at 0 °C. The mixture was stirred for 24 h

at room temperature. Then more Me₃SiCl, as a solution of Me₃-

SiCl (0.86 g, 7.9 mmol) in CH₃CN (9 mL), was added at 0 °C,

and the reaction mixture was stirred for 8 h at room temper-

ature. The solids were filtered off through Celite, and the cake

was washed with CH₂Cl₂. The filtrate was poured into ice-

cold saturated NaHCO₃. The aqueous phase was repeatedly

extracted with CH₂Cl₂. The combined extracts were washed

with saturated NaHCO₃and brine. The extracts were dried

over Na₂SO₄and concentrated. The residue was purified by

column chromatography on silica gel (hexanes/EtOAc 2:1) to

give 6c (1.83 g, 63%) as an oil: ¹H NMR (500 MHz, CDCl₃) δ

7.79 (br s, 1H), 7.61-7.69 (m, 3H), 7.28 (d, J ) 8.5 Hz, 2H),

7.02 (d, J ) 7.0 Hz, 2H), 6.84-6.92 (m, 5H), 5.15 (d, J ) 8.5

Hz, 1H), 4.83 (d, J ) 12.5 Hz, 1H), 4.82 (d, J ) 10.5 Hz, 1H),

4.67 (d, J ) 11.0 Hz, 1H), 4.46 (d, J ) 12.0 Hz, 1H), 4.34 (dd,

J ) 10.5, 8.5 Hz, 1H), 4.10 (dd, J ) 11.0, 8.5 Hz, 1H), 3.90-

3.94 (m, 1H), 3.80 (s, 3H), 3.69-3.79 (m, 3H), 3.60 (s, 3H),

3.51-3.54 (m, 1H), 3.37 (dt, J ) 9.5, 6.5 Hz, 1H), 2.10 (dd, J

) 7.0, 6.5 Hz, 1H), 1.92-2.03 (m, 2H), 1.31-1.44 (m, 4H),

1.01-1.13 (m, 2H); ¹³C NMR (125 MHz, CDCl₃) δ 173.9, 159.4,

138.0, 133.7, 130.0, 129.8, 128.0, 127.9, 127.3, 123.2, 113.9,

98.3, 79.10, 79.05, 75.20, 74.76, 74.76, 69.39, 61.82, 55.92,

55.26, 51.40, 33.67, 28.90, 25.23, 24.28; HRMS (M + Cs) calcd

for C₃₆H₄₁O₁₀NCs 780.1781, found 780.1803.

Or th o Ester 9. To a solution of 1a (69.5 mg, 0.1074 mmol)

and 2 (50.0 mg, 0.07158 mmol) in CH₂Cl₂(5 mL) was added 4

Å molecular sieves (600 mg), and the mixture was stirred for

30 min at room temperature and then cooled to - 20 °C. NIS

(25.5 mg, 0.1077 mmol) and TfOH (45 µL, 0.3 M etheral

solution) were added to the mixture, and this mixture was

stirred for 20 min at -20 °C. To the reaction mixture was

added a solution of 6a (119.0 mg, 0.2147 mmol) in CH₂Cl₂(2

mL), NIS (25.5 mg, 0.1077 mmol), and TfOH (50 µL, 0.3 M

etheral solution). The reaction mixture was stirred for 30 min

at -20 °C. The course of the reaction was monitored by TLC.

Et₃N (0.5 mL) was then added to the mixture. The precipitate

was filtered off, and the filtrate was successively washed with

saturated aqueous Na₂S₂O₃, NaHCO₃, and brine. The organic

layer was dried over Na₂SO₄and concentrated. The residue

was purified by column chromatography on silica gel (hexanes/

EtOAc 4:1 to 3:1) to give 9 (94.8 mg, 80%) as a syrup: ¹H NMR

2420 J . Org. Chem., Vol. 65, No. 8, 2000

Ye and Wong

mL), NIS (24.5 mg, 0.1033 mmol), and TfOH (45 µL, 0.3 M

etheral solution). The reaction mixture was stirred for 30 min

at -20 °C. Et₃N (0.5 mL) was then added to the mixture. The

precipitate was filtered off, and the filtrate was successively

washed with saturated aqueous Na₂S₂O₃, NaHCO₃, and brine.

The organic layer was dried over Na₂SO₄and concentrated.

The residue was purified by column chromatography on silica

gel (hexanes/EtOAc 4:1 to 3:1) to give 15 (36.1 mg, 87%) as a

syrup and recovery of 14 (46.3 mg) and 6a (114.0 mg): ¹H NMR

(500 MHz, CDCl₃) δ 8.02 (d, J ) 7.5 Hz, 2H), 7.62-7.67 (m,

5H), 7.49 (t, J ) 8.0 Hz, 2H), 7.33-7.44 (m, 6H), 5.44 (t, J )

2.5 Hz, 1H), 5.29 (t, J ) 2.5 Hz, 1H), 4.87 (d, J ) 6.5 Hz, 1H),

4.76 (dt, J ) 6.5, 2.0 Hz, 1H), 4.28 (dd, J ) 8.5, 5.5 Hz, 1H),

3.89 (t, J ) 9.0 Hz, 1H), 3.85 (dd, J ) 9.5, 5.5 Hz, 1H), 2.64-

2.73 (m, 2H), 2.25 (t, J ) 7.5 Hz, 2H), 2.17 (s, 3H), 1.08 (s,

9H); ¹³C NMR (125 MHz, CDCl₃) δ 207.1, 165.0, 135.6, 135.5,

137.7, 133.3, 133.0, 129.8, 129.8, 128.9, 128.6, 127.7, 118.4,

93.8, 72.64, 72.00, 69.78, 67.33, 62.98, 37.86, 29.88, 27.19,

26.89, 19.22; HRMS (M + Cs) calcd for C₃₄H₃₈O₈SiCs 735.1390,

found 735.1410.

p-Meth ylp h en yl 2-Deoxy-2-a zid o-3,4,6-tr i-O-a cetyl-1-

th io-^D-ga la ctop yr a n osid e (20). To a mixture of 2-deoxy-2-

azido-1,3,4,6-tetra-O-acetyl-^D-galactopyranoside (19)¹⁸(3.5 g,

9.38 mmol) and p-thiocresol (1.75 g, 14.07 mmol) in CH₂Cl₂

(60 mL) was added boron trifluoride diethyl etherate (1.54 mL,

12.19 mol) at 0 °C. The mixture was then stirred overnight at

room temperature. The reaction mixture was diluted with CH₂-

Cl₂and washed with saturated NaHCO₃and water. The

organic layer was dried over Na₂SO₄. The solvent was removed,

and the residue was purified by column chromotography on

silica gel (hexanes/EtOAc 3:1) to give 20 (2.78 g, 68%) as a

syrup and recovery of 19 (0.69 g): ¹H NMR (500 MHz, CDCl₃)

(R/â ) 1.2:1), δ 7.50 (d, J ) 8.0 Hz, 2H), 7.40 (d, J ) 8.0 Hz,

2H), 7.12-7.16 (m, 4H), 5.61 (d, J ) 5.5 Hz, 1H, H-1 of

R-isomer), 5.48 (dd, J ) 3.0, 1.0 Hz, 1H), 5.34 (dd, J ) 3.5, 1.0

Hz, 1H), 5.17 (dd, J ) 11.0, 3.5 Hz, 1H), 4.85 (dd, J ) 10.0,

3.0 Hz, 1H), 4.77 (t, J ) 6.5 Hz, 1H), 4.46 (d, J ) 10.0 Hz, 1H,

H-1 of â-isomer), 4.29 (dd, J ) 11.0, 5.5 Hz, 1H), 4.16 (dd, J )

11.0, 6.5 Hz, 1H), 4.07-4.12 (m, 3H), 3.86 (dt, J ) 1.0, 6.5 Hz,

1H), 3.63 (t, J ) 10.0 Hz, 1H), 2.36 (s, 3H), 2.33 (s, 3H), 2.15

(s, 3H), 2.08 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H),

1H), 4.89 (d, J ) 11.3 Hz, 1H), 4.75 (s, 2H), 4.54 (d, J ) 11.3

Hz, 1H), 4.49 (t, J ) 6.5 Hz, 1H), 4.39-4.46 (m, 3H), 4.04 (d,

J ) 1.6 Hz, 1H), 3.78 (dd, J ) 10.6, 2.7 Hz, 1H), 3.61 (dd, J )

9.4, 6.9 Hz, 1H), 3.53 (dd, J ) 9.4, 6.1 Hz, 1H), 2.29 (s, 3H);

¹³C NMR (100 MHz, CDCl₃) δ 138.19, 137.85, 137.78, 137.36,

132.84, 129.73, 129.49, 128.53, 128.37, 128.28, 127.99, 127.96,

127.82, 127.74, 127.66, 87.93, 79.11, 74.84, 73.42, 73.42, 72.38,

70.38, 68.63, 60.36, 21.08; HRMS (M + Cs) calcd for C₃₄H₃₅O₄N₃-

SCs 714.1403, found 714.1429.

p-Meth ylp h en yl 2,3,4,6-Tetr a -O-ben zyl-1-th io-r-^D-m a n -

n op yr a n osid e (1e). Compound 14 (1.82 g, 4.01 mmol) was

treated with NaOMe/MeOH (25 wt %, 0.6 mL) in MeOH (35

mL) at room temperature. After 3 h, the mixture was neutral-

ized (IRC-50 resin, weak acid) and concentrated to give solids.

To a solution of the above solids in dry DMF (35 mL) was

added NaH (95%, 0.61 g, 24.06 mmol) in portions. After the

mixture was stirred for 15 min, benzyl bromide (4.2 g, 24.06

mmol) was then added at 0 °C. The reaction mixture was

stirred for 6 h at room temperature. MeOH (6 mL) was then

added to the mixture. The reaction mixture was poured to ice-

water and extracted with EtOAc. The combined organic liquid

was dried over Na₂SO₄. The solvent was removed, and the

residue was subjected to a column chromatography on silica

gel (hexanes/EtOAc 8:1) to give 1e (1.97 g, 76%) as an oil: ¹H

NMR (500 MHz, CDCl₃) δ 7.22-7.37 (m, 20H), 7.20 (dd, J )

7.5, 1.5 Hz, 2H), 7.03 (d, J ) 8.5 Hz, 2H), 5.55 (d, J ) 1.5 Hz,

1H), 4.91 (d, J ) 11.0 Hz, 1H), 4.72 (d, J ) 12.0 Hz, 1H), 4.57-

4.65 (m, 4H), 4.53 (d, J ) 11.0 Hz, 1H), 4.48 (d, J ) 12.0 Hz,

1H), 4.28-4.31 (m, 1H), 4.05 (t, J ) 9.5 Hz, 1H), 3.99 (dd, J )

2.5, 2.0 Hz, 1H), 3.87 (dd, J ) 9.5, 3.5 Hz, 1H), 3.84 (dd, J )

11.0, 5.0 Hz, 1H), 3.75 (dd, J ) 11.0, 1.5 Hz, 1H), 2.30 (s, 3H);

¹³C NMR (125 MHz, CDCl₃) δ 138.4, 138.4, 138.2, 137.9, 137.5,

132.1, 130.5, 129.7, 128.4, 128.3, 128.2, 127.9, 127.9, 127.8,

127.7, 127.6, 127.6, 127.4, 85.95, 80.11, 76.08, 75.16, 75.00,

73.23, 72.66, 72.02, 71.76, 69.20, 21.08; HRMS (M + Cs) calcd

for C₄₁H₄₂O₅SCs 779.1807, found 779.1828.

5-Meth oxyca r bon ylp en tyl 2,3,4,6-Tetr a -O-a cetyl-â-D-

ga la ctop yr a n osid e (23). To a mixture of ^D-galactose pen-

taacetate (22) (8.0 g, 20.49 mmol), methyl 6-hydroxylhexate

(4.49 g, 30.74 mmol), and 4 Å molecular sieves (5 g) in CH₂Cl₂

(200 mL) was added BF₃‚OEt₂(7.8 mL, 61.47 mmol) at 0 °C.

The reaction mixture was then stirred for 6 h at room

temperature. Water (1.6 mL) was added to the mixture, and

the mixture was stirred for 15 min. The reaction mixture was

filtered through Celite, and the filtrate was diluted with CH₂-

Cl₂. The organic layer was washed with saturated NaHCO₃

and brine and dried over Na₂SO₄. The solvent was removed,

and the residue was purified by column chromatography on

silica gel (hexanes/EtOAc 2.5:1) to give product (5.51 g, 56%)

as an oil: ¹H NMR (400 MHz, CDCl₃) δ 5.39 (dd, J ) 3.4, 1.0

Hz, 1H), 5.20 (dd, J ) 10.5, 8.0 Hz, 1H), 5.01 (dd, J ) 10.4,

3.5 Hz, 1H), 4.45 (d, J ) 7.9 Hz, 1H), 4.10-4.21 (m, 2H), 3.85-

3.92 (m, 2H), 3.67 (s, 3H), 3.48 (dt, J ) 9.5, 6.5 Hz, 1H), 2.31

(t, J ) 7.6 Hz, 2H), 2.15 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 1.99

(s, 3H), 1.54-1.67 (m, 4H), 1.30-1.42 (m, 2H); ¹³C NMR (125

MHz, CDCl₃) δ 174.0, 170.4, 170.3, 170.2, 169.4, 101.3, 70.93,

70.57, 69.84, 68.87, 67.00, 61.26, 51.48, 33.91, 29.06, 25.35,

2.00 (s, 3H); HRMS (M + Cs) calcd for

570.0311, found 570.0326.

C₁₉H₂₃O₇N₃SCs

p-Meth ylp h en yl 3,4,6-Tr i-O-ben zyl-2-d eoxy-2-a zid o-1-

th io-â-^D-galactopyr an oside (1d) an d p-Meth ylph en yl 3,4,6-

Tr i-O-ben zyl-2-d eoxy-2-a zid o-1-th io-r-^D-ga la ctop yr a n o-

sid e (21). Compound 20 (926.0 mg, 2.12 mmol) was treated

with NaOMe/MeOH (25 wt %, 0.5 mL) in MeOH (18 mL) at

room temperature. After 3 h, the mixture was neutralized

(IRC-50 resin, weak acid) and concentrated to give semisolids.

To a solution of above semisolids in dry DMF (15 mL) was

added NaH (95%, 0.32 g, 12.7 mmol) in portions. After the

mixture was stirred for 10 min, benzyl bromide (2.2 g, 12.7

mmol) was then added at 0 °C. The reaction mixture was

stirred for 3 h at room temperature. MeOH (4 mL) was then

added to the mixture. The reaction mixture was poured to ice-

water and extracted with EtOAc. The combined organic liquid

was dried over Na₂SO₄. The solvent was removed, and the

residue was subjected to a column chromatography on silica

gel (hexanes/EtOAc 8:1) to give 1d (532.6 mg, 43%) and its

R-anomeric isomer 21 (641.4 mg, 52%) as thick oils. Compound

1d : ¹H NMR (400 MHz, CDCl₃) δ 7.46 (d, J ) 8.2 Hz, 2H),

7.19-7.39 (m, 15H), 7.00 (dd, J ) 8.4, 0.6 Hz, 2H), 4.86 (d, J

) 11.4 Hz, 1H), 4.71 (d, J ) 11.6 Hz, 1H), 4.65 (d, J ) 11.6

Hz, 1H), 4.51 (d, J ) 11.4 Hz, 1H), 4.47 (d, J ) 11.7 Hz, 1H),

4.42 (d, J ) 11.7 Hz, 1H), 4.33 (d, J ) 10.1 Hz, 1H), 3.93 (d,

J ) 2.2 Hz, 1H), 3.79 (t, J ) 9.9 Hz, 1H), 3.63 (d, J ) 6.7 Hz,

1H), 3.62 (s, 1H), 3.55 (dt, J ) 0.6, 6.7 Hz, 1H), 3.40 (dd, J )

9.8, 2.7 Hz, 1H), 2.29 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ

138.41, 138.02, 137.69, 137.36, 133.34, 129.57, 128.46, 128.39,

128.09, 127.92, 127.87, 127.79, 127.58, 127.40, 86.45, 82.42,

77.22, 74.30, 73.50, 72.31, 71.99, 68.36, 61.34, 21.11; HRMS

(M + Cs) calcd for C₃₄H₃₅O₄N₃SCs 714.1403, found 714.1429.

Its R-anomeric isomer 21: ¹H NMR (400 MHz, CDCl₃) δ 7.23-

7.43 (m, 17H), 7.02 (d, J ) 7.9 Hz, 2H), 5.53 (d, J ) 5.4 Hz,

24.55, 20.71, 20.66, 20.58; HRMS (M + Cs) calcd for C₂₁H₃₂O₁₂

Cs 609.0948, found 609.0967.

-

5-Meth oxyca r bon ylp en tyl 4,6-O-Ben zylid en e-â-^D-ga -

la ctop yr a n osid e (24). Compound 23 (5.2 g, 10.92 mmol) was

treated with NaOMe/MeOH (25 wt %, 0.4 mL) in MeOH (140

mL) at room temperature. After 4 h, the mixture was neutral-

ized (IRC-50 resin, weak acid) and concentrated to give white

solids. To a mixture of above white solids, benzaldehyde

dimethyl acetal (2.34 g, 15.6 mmol), and dry acetonitrile (70

mL) was added 10-camphorsulfonic acid (49.3 mg) at room

temperature. The mixture was stirred for 4 h, and Et₃N (2

mL) was then added. The solvent was removed to give white

solids. The crude product was subjected to recrystallization

(EtOAc/hexanes) to give 24 (3.76 g, 87%) as a solid: ¹H NMR

(500 MHz, CDCl₃) δ 7.49-7.52 (m, 2H), 7.34-7.39 (m, 3H),

5.56 (s, 1H), 4.34 (dd, J ) 12.5, 1.5 Hz, 1H), 4.27 (d, J ) 7.5

Hz, 1H), 4.22 (dd, J ) 3.5, 1.0 Hz, 1H), 4.09 (dd, J ) 12.5, 2.0

Hz, 1H), 3.99 (dt, J ) 9.0, 6.5 Hz, 1H), 3.76 (dt, J ) 1.5, 8.5

One-Pot Oligosaccharide Synthesis

J . Org. Chem., Vol. 65, No. 8, 2000 2421

Hz, 1H), 3.71 (dd, J ) 8.5, 3.5 Hz, 1H), 3.67 (s, 3H), 3.51 (dt,

J ) 9.5, 6.5 Hz, 1H), 3.48 (d, J ) 1.0 Hz, 1H), 2.77 (br. s, 1H),

2.57 (d, J ) 8.5 Hz, 1H), 2.34 (t, J ) 7.5 Hz, 2H), 1.61-1.73

(m, 4H), 1.37-1.46 (m, 2H); ¹³C NMR (125 MHz, CDCl₃) δ

174.3, 137.5, 129.2, 128.2, 126.4, 102.8, 101.4, 75.30, 72.68,

71.73, 69.50, 69.15, 66.64, 51.54, 33.79, 28.89, 25.42, 24.44;

HRMS (M + Na) calcd for C₂₀H₂₈O₈Na 419.1682, found

419.1669.

137.5, 129.0, 128.4, 128.3, 128.2, 128.1, 128.0, 127.7, 127.5,

127.5, 127.4, 126.2, 102.2, 100.8, 98.0, 79.65, 77.69, 76.64,

76.07, 74.78, 73.81, 73.34, 73.05, 72.83, 69.84, 68.99, 66.79,

65.94, 51.48, 40.66, 33.94, 29.19, 25.56, 24.70, 16.66; HRMS

(M + Cs) calcd for C₄₉H₅₇O₁₃ClCs 1021.2542, found 1021.2582.

5-Meth oxyca r bon ylp en tyl 2-O-(2,3,4-Tr i-O-ben zyl-r-L-

fu cop yr a n osyl)-4,6-O-b en zylid en e-â-^D-ga la ct op yr a n o-

sid e (6d ). Compound 27 (1.18 g, 1.33 mmol) was treated with

NaOMe/MeOH (25 wt %, 0.5 mL) in MeOH (50 mL) at room

temperature. After 3 h, the mixture was neutralized (IRC-50

resin, weak acid) and concentrated. The residue was purified

by column chromatography on silica gel (hexanes/EtOAc 2:1)

to give 6d (1.07 g, 99%) as a thick oil: ¹H NMR (400 MHz,

CDCl₃) δ 7.53 (dd, J ) 7.5, 2.0 Hz, 2H), 7.22-7.40 (m, 18H),

5.54 (s, 1H), 5.25 (d, J ) 3.6 Hz, 1H), 4.97 (d, J ) 11.6 Hz,

1H), 4.73-4.83 (m, 4H), 4.66 (d, J ) 11.6 Hz, 1H), 4.27-4.37

(m, 2H), 4.19 (br. s, 1H), 4.17 (q, J ) 6.5 Hz, 1H), 4.03-4.09

(m, 2H), 3.97 (dd, J ) 10.1, 2.7 Hz, 1H), 3.88 (dt, J ) 9.2, 7.0

Hz, 1H), 3.82-3.84 (m, 2H), 3.75 (br. s, 1H), 3.68 (d, J ) 2.0

Hz, 1H), 3.64 (s, 3H), 3.44 (dt, J ) 9.2, 6.9 Hz, 1H), 3.39 (br.

s, 1H), 2.28 (t, J ) 7.4 Hz, 2H), 1.54-1.64 (m, 4H), 1.28-1.40

(m, 2H), 1.12 (d, J ) 6.5 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃)

δ 174.07, 138.76, 138.64, 137.78, 137.68, 129.06, 128.37,

128.27, 128.16, 128.13, 127.79, 127.53, 127.48, 127.35, 126.53,

101.77, 101.39, 99.25, 79.70, 77.72, 77.61, 75.54, 74.76, 73.71,

73.58, 72.88, 69.24, 69.12, 66.78, 66.54, 51.46, 33.94, 29.33,

25.54, 24.73, 16.69; HRMS (M + Cs) calcd for C₄₇H₅₆O₁₂Cs

945.2826, found 945.2856.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-[2-O-ben zoyl-3-O-(2,3,4,6-tetr a -O-ben zyl-r-^D-

glu cop yr a n osyl)-4-O-(2,3,4-tr i-O-ben zyl-r-^L-fu cop yr a n o-

syl)-6-O-ter t-bu tyld ip h en ylsilyl-â-^D-ga la ctop yr a n osyl]-6-

O-p-m eth oxyben zyl-â-^D-glu copyr an oside (28). To a solution

of p-methylphenyl 2-O-benzoyl-4-O-(2,3,4-tri-O-benzyl-R-^L-fu-

copyranosyl)-6-O-tert-butyldiphenylsilyl-1-thio-â-^D-galactopy-

ranoside (2e) (20.0 mg, 0.01916 mmol) and p-methylphenyl

2,3,4,6-tetra-O-benzyl-â-^D-glucopyranoside (1b ) (18.6 mg,

0.02874 mmol) in CH₂Cl₂(2 mL) was added 4 Å molecular

sieves (300 mg), and the mixture was stirred for 20 min at

room temperature under argon. At the same time, methyl

disulfide (10.9 mg, 115.0 µmol) and methyl trifluoromethane-

sulfonate (19.1 mg, 115.0 µmol) were mixed in a vial to form

solids. The solids in CH₂Cl₂(0.5 mL) were then added to the

above stirred mixture at 0 °C. The reaction mixture was stirred

at 0 °C for 30 min and then at room temperature for 1 h. To

the reaction mixture was added a solution of 5-methoxycar-

bonylpentyl 3-O-benzyl-6-O-p-methoxybenzyl-2-deoxy-2-ph-

thalimido-â-^D-glucopyranoside (6b) (37.2 mg, 0.05748 mmol)

in CH₂Cl₂(0.5 mL), NIS (6.8 mg, 0.02874 mmol), and TfOH

(25 µL, 0.3 M etheral solution). The reaction mixture was

stirred for 30 min at room temperature. The course of the

reaction was monitored by TLC. Et₃N (0.6 mL) was then added

to the mixture. The precipitate was filtered off, and the filtrate

was successively washed with saturated aqueous Na₂S₂O₃,

NaHCO₃, and brine. The organic layer was dried over Na₂-

SO₄and concentrated. The residue was purified by column

chromatography on silica gel (hexanes/EtOAc 3:1 to 2:1) to give

28 (20.4 mg, 51%) as a thick oil: ¹H NMR (400 MHz, CDCl₃)

δ 6.55-7.98 (m, 63H), 3.15-6.02 (m, 52H), 1.85-1.93 (m, 2H),

1.22-1.32 (m, 4H), 1.08 (s, 9H), 0.99-1.03 (m, 2H), 0.96 (d, J

) 6.5 Hz, 3H); HRMS (M + Cs) calcd for C₁₂₆H₁₃₅O₂₅NSiCs

2222.8147, found 2222.8286.

5-Met h oxyca r b on ylp en t yl

3-O-Ch lor oa cet yl-4,6-O-

ben zylid en e-â-^D-ga la ctop yr a n osid e (25) a n d 5-Meth oxy-

ca r bon ylp en tyl 2,3-Di-O-ch lor oa cetyl-4,6-O-ben zylid en e-

â-^D-ga la ctop yr a n osid e (26). To a cold (-20 °C) solution of

compound 24 (500 mg, 1.26 mmol) in pyridine (0.8 mL), Et₃N

(0.8 mL), and CH₂Cl₂(10 mL) was added slowly chloroacetyl

chloride (160 mg, 1.39 mmol). The mixture was stirred for 2 h

at - 20 °C. The reaction mixture was then diluted with CH₂-

Cl₂and washed with saturated NaHCO₃and brine. The dried

organic solvent (Na₂SO₄) was concentrated. The residue was

subjected to a column chromatography on silica gel (hexanes/

EtOAc 2:1) to give 25 (295.1 mg, 50%) as a thick oil and 26

(173.8 mg, 25%) as a syrup. For compound 25: ¹H NMR (500

MHz, CDCl₃) δ 7.47-7.51 (m, 2H), 7.32-7.38 (m, 3H), 5.49 (s,

1H), 4.92 (dd, J ) 10.0, 3.5 Hz, 1H), 4.39 (d, J ) 3.5 Hz, 1H),

4.32 (d, J ) 7.5 Hz, 1H), 4.30 (d, J ) 12.5 Hz, 1H), 4.17 (ABq,

J ) 15.5 Hz, 2H), 4.05 (dd, J ) 12.5, 1.5 Hz, 1H), 3.94-4.00

(m, 2H), 3.65 (s, 3H), 3.51 (dt, J ) 9.0, 7.0 Hz, 1H), 3.48 (s,

1H), 2.32 (t, J ) 7.5 Hz, 2H), 2.04 (d, J ) 2.0 Hz, 1H), 1.58-

1.69 (m, 4H), 1.35-1.43 (m, 2H); ¹³C NMR (125 MHz, CDCl₃)

δ 174.2, 167.2, 137.4, 128.9, 128.1, 126.2, 102.8, 100.7, 75.28,

73.03, 69.42, 68.84, 68.16, 66.05, 51.44, 40.84, 33.63, 28.63,

25.16, 24.15; HRMS (M + Cs) calcd for C₂₂H₂₉O₉ClCs 605.0554,

found 605.0579. For compound 26: ¹H NMR (500 MHz, CDCl₃)

δ 7.47-7.52 (m, 2H), 7.34-7.40 (m, 3H), 5.50 (s, 1H), 5.42 (dd,

J ) 10.5, 8.0 Hz, 1H), 5.06 (dd, J ) 10.5, 4.0 Hz, 1H), 4.53 (d,

J ) 8.0 Hz, 1H), 4.43 (d, J ) 3.5 Hz, 1H), 4.33 (dd, J ) 12.5,

1.5 Hz, 1H), 4.08 (dd, J ) 12.0, 1.5 Hz, 1H), 4.07 (s, 2H), 4.05

(s, 2H), 3.93 (dt, J ) 9.5, 6.0 Hz, 1H), 3.66 (s, 3H), 3.53 (d, J

) 1.0 Hz, 1H), 3.47 (dt, J ) 9.5, 6.5 Hz, 1H), 2.30 (t, J ) 7.5

Hz, 2H), 1.52-1.66 (m, 4H), 1.31-1.41 (m, 2H); ¹³C NMR (125

MHz, CDCl₃): δ 174.0, 167.1, 165.9, 137.1, 129.1, 128.1, 126.2,

101.0, 100.4, 73.32, 73.06, 70.14, 69.23, 68.72, 66.11, 51.42,

40.54, 40.47, 33.83, 28.94, 25.36, 24.49; HRMS (M + Cs) calcd

for C₂₄H₃₀O₁₀Cl₂Cs 681.0270, found 681.0240.

5-Meth oxyca r bon ylp en tyl 2-O-(2,3,4-Tr i-O-ben zyl-r-^L-

fu cop yr a n osyl)-3-O-ch lor oa cetyl-4,6-O-ben zylid en e-â-^D-

ga la ctop yr a n osid e (27). To a solution of 25 (1.01 g, 2.14

mmol), p-methylphenyl 2,3,4,-tri-O-benzyl-1-thio-â-^L-fuco-

pyranoside (1c) (1.73 g, 3.21 mmol), and 2,6-di-tert-butyl-4-

methylpyridine (672 mg, 3.21 mmol) in CH₂Cl₂(40 mL) was

added 4 Å molecular sieves (4.0 g), and the mixture was stirred

for 20 min at room temperature. At the same time, methyl

disulfide (610 mg, 6.41 mmol) and methyl trifluoromethane-

sulfonate (1.06 g, 6.41 mmol) were mixed in a vial to form

solids. The solids in CH₂Cl₂(10 mL) were then added to the

above stirred mixture at 0 °C. The reaction mixture was stirred

at 0 °C for 30 min and then at room temperature for 1 h. Et₃N

(2.5 mL) was then added to the mixture. The precipitate was

filtered off, and the filtrate was diluted with CH₂Cl₂and

washed with NaHCO₃and brine. The organic layer was dried

over Na₂SO₄and concentrated. The residue was purified by

column chromatography on silica gel (hexanes/EtOAc 4:1) to

give product 27 (1.19 g, 83%) as a thick oil: ¹H NMR (500 MHz,

CDCl₃) δ 7.52 (dd, J ) 7.5, 1.5 Hz, 2H), 7.22-7.40 (m, 18H),

5.50 (s, 1H), 5.23 (d, J ) 3.5 Hz, 1H), 5.12 (dd, J ) 10.0, 4.0

Hz, 1H), 4.99 (d, J ) 12.0 Hz, 1H), 4.79 (d, J ) 11.5 Hz, 1H),

4.77 (d, J ) 10.0 Hz, 1H), 4.72 (d, J ) 11.5 Hz, 1H), 4.65 (d,

J ) 11.5 Hz, 1H), 4.64 (d, J ) 11.5 Hz, 1H), 4.46 (d, J ) 7.5

Hz, 1H), 4.37 (d, J ) 4.0 Hz, 1H), 4.32 (d, J ) 12.0 Hz, 1H),

4.22 (q, J ) 6.5 Hz, 1H), 4.12 (dd, J ) 9.5, 7.5 Hz, 1H), 4.03-

4.08 (m, 2H), 3.91 (dt, J ) 9.0, 7.0 Hz, 1H), 3.86 (dd, J ) 10.5,

3.0 Hz, 1H), 3.76 (d, J ) 15.5 Hz, 1H), 3.69 (d, J ) 15.5 Hz,

1H), 3.66 (dd, J ) 6.0, 4.0 Hz, 1H), 3.65 (s, 3H), 3.48 (s, 1H),

3.45 (dt, J ) 9.0, 7.0 Hz, 1H), 2.29 (t, J ) 7.5 Hz, 2H), 1.57-

5-Meth oxyca r bon ylp en tyl 2-O-(2,3,4-Tr i-O-ben zyl-r-^L-

fu cop yr a n osyl)-3-O-[2-O-ben zoyl-3-O-(2,3,4-tr i-O-ben zyl-

r-^L-fu cop yr a n osyl)-4-O-levu lin yl-6-O-ter t-bu tyld ip h en yl-

s ily l-â-^D-g a la c t o p y r a n o s y l]-4,6-O -b e n z y lid e n e -â-D -

ga la ctop yr a n osid e (29) a n d 5-Meth oxyca r bon ylp en tyl

2-O-(2,3,4-Tr i-O-b e n zyl-r-^L-fu cop yr a n osyl)-3-O-[2-O-

b en zoyl-3-O-(2,3,4-t r i-O-b en zyl-â-^L-fu cop yr a n osyl)-4-O-

levu lin yl-6-O-ter t-bu tyld ip h en ylsilyl-r-^D-ga la ctop yr a n o-

syl]-4,6-O-ben zylid en e-â-^D-ga la ctop yr a n osid e (30). To a

solution of 2b (28.0 mg, 0.03857 mmol) and 1c (31.2 mg,

0.05785 mmol) in CH₂Cl₂(2 mL) were added 4 Å molecular

sieves (400 mg) and 2,6-di-tert-butyl-4-methylpyridine (12.1

mg, 0.05785 mmol), and the mixture was stirred for 20 min

1.63 (m, 4H), 1.31-1.37 (m, 2H), 1.10 (d, J ) 6.5 Hz, 3H); ¹³

NMR (125 MHz, CDCl₃) δ 174.0, 167.0, 138.8, 138.7, 138.3,

C

2422 J . Org. Chem., Vol. 65, No. 8, 2000

Ye and Wong

at room temperature under argon. At the same time, methyl

disulfide (22.0 mg, 0.2314 mmol) and methyl trifluoromethane-

sulfonate (38.4 mg, 0.2314 mmol) were mixed in a vial to form

solids. The solids in CH₂Cl₂(0.8 mL) were then added to the

above stirred mixture at 0 °C. The reaction mixture was stirred

at 0 °C for 30 min and then at room temperature for 1.5 h. To

the reaction mixture, after the addition of a solution of 6d (93.9

mg, 0.1157 mmol) in CH₂Cl₂(0.5 mL), the solids formed by

mixing methyl disulfide (22.0 mg, 0.2314 mmol) and methyl

trifluoromethanesulfonate (38.4 mg, 0.2314 mmol) were added.

The reaction mixture was stirred overnight. Et₃N (0.6 mL) was

then added to the mixture. The precipitate was filtered off,

and the cake was washed with CH₂Cl₂. The filtrate was

washed with saturated aqueous NaHCO₃and brine. The

organic layer was dried over Na₂SO₄and concentrated. The

residue was purified by column chromatography on silica gel

(hexanes/EtOAc 4:1 to 3:1) to give 29 (21.2 mg, 30%) and 30

(16.9 mg, 24%) as thick oils. For compound 29: ¹H NMR (400

MHz, CDCl₃) δ 7.89 (dd, J ) 8.1, 1.0 Hz, 2H), 7.59-7.63 (m,

4H), 7.51 (t, J ) 7.5 Hz, 1H), 7.09-7.44 (m, 41H), 6.93 (dd, J

) 8.1, 1.5 Hz, 2H), 5.77 (s, 1H), 5.53 (d, J ) 3.6 Hz, 1H), 5.50

(dd, J ) 10.1, 8.0 Hz, 1H), 5.40 (d, J ) 3.6 Hz, 1H), 5.14 (d, J

) 3.4 Hz, 1H), 4.94 (d, J ) 11.6 Hz, 1H), 4.88 (d, J ) 11.4 Hz,

1H), 4.85 (d, J ) 11.0 Hz, 1H), 4.74 (d, J ) 11.8 Hz, 1H), 4.70

(d, J ) 12.5 Hz, 2H), 4.67 (d, J ) 8.5 Hz, 1H), 4.65 (d, J )

12.0 Hz, 1H), 4.63 (d, J ) 11.6 Hz, 1H), 4.59 (d, J ) 11.6 Hz,

1H), 4.57 (d, J ) 8.0 Hz, 1H), 4.32 (t, J ) 6.4 Hz, 1H), 4.07-

4.21 (m, 7H), 4.02 (dd, J ) 6.2, 2.2 Hz, 1H), 4.00 (dd, J ) 10.0,

3.6 Hz, 1H), 3.65-3.87 (m, 10H), 3.64 (s, 3H), 3.61 (d, J ) 1.9

Hz, 1H), 3.37 (dt, J ) 9.6, 5.8 Hz, 1H), 2.98 (dt, J ) 9.6, 5.6

Hz, 1H), 2.46-2.68 (m, 4H), 2.17 (t, J ) 7.5 Hz, 2H), 1.99 (s,

3H), 1.41-1.49 (m, 2H), 1.20-1.30 (m, 2H), 1.15 (d, J ) 6.5

Hz, 3H), 1.04-1.11 (m, 2H), 1.01 (s, 9H), 1.00 (d, J ) 6.5 Hz,

3H); ¹³C NMR (100 MHz, CDCl₃) δ 206.03, 174.00, 172.02,

164.55, 139.02, 138.90, 138.59, 138.52, 138.35, 138.30, 136.51,

135.60, 135.49, 133.16, 132.97, 132.85, 129.85, 129.81, 129.67,

129.61, 129.30, 128.52, 128.45, 128.28, 128.21, 128.14, 128.12,

128.04, 127.86, 127.77, 127.74, 127.56, 127.51, 127.35, 127.26,

127.23, 126.99, 126.92, 105.09, 101.66, 100.67, 98.52, 95.37,

79.79, 79.32, 78.65, 77.82, 77.40, 76.39, 76.16, 75.57, 75.02,

74.79, 74.75, 73.76, 73.42, 73.31, 72.82, 72.70, 72.46, 72.17,

71.83, 69.17, 68.77, 68.54, 67.25, 66.03, 60.96, 51.47, 38.35,

33.89, 29.68, 29.21, 28.42, 26.68, 25.74, 24.71, 19.02, 16.53,

16.39; HRMS (M + Cs) calcd for C₁₀₈H₁₂₂O₂₄SiCs 1963.7150,

found 1963.7269. For compound 30: ¹H NMR (500 MHz,

CDCl₃) δ 7.88 (dd, J ) 7.5, 1.5 Hz, 2H), 7.65-7.68 (m, 4H),

7.55 (d, J ) 7.0 Hz, 2H), 7.51 (d, J ) 7.5 Hz, 2H), 7.05-7.46

(m, 38H), 6.91 (d, J ) 7.0 Hz, 2H), 5.45 (s, 1H), 5.44 (dd, J )

10.0, 8.0 Hz, 1H), 5.20 (d, J ) 12.0 Hz, 1H), 5.10 (d, J ) 4.0

Hz, 1H), 5.05 (d, J ) 4.0 Hz, 1H), 5.04 (d, J ) 4.0 Hz, 1H),

4.94 (d, J ) 11.0 Hz, 1H), 4.88 (d, J ) 11.5 Hz, 1H), 4.83 (d,

J ) 8.0 Hz, 1H), 4.81 (d, J ) 13.0 Hz, 1H), 4.78 (d, J ) 11.5

Hz, 1H), 4.72 (d, J ) 11.5 Hz, 1H), 4.66 (d, J ) 12.0 Hz, 1H),

4.62 (d, J ) 12.0 Hz, 1H), 4.58 (d, J ) 11.5 Hz, 1H), 4.52 (d,

J ) 11.0 Hz, 1H), 4.22 (d, J ) 8.0 Hz, 1H), 4.21 (d, J ) 12.0

Hz, 1H), 4.17 (q, J ) 6.5 Hz, 1H), 4.11 (d, J ) 11.5 Hz, 1H),

4.07 (d, J ) 12.0 Hz, 1H), 4.01 (q, J ) 6.5 Hz, 1H), 3.98 (d, J

) 4.0 Hz, 1H), 3.97 (dd, J ) 10.0, 2.5 Hz, 1H), 3.88 (dd, J )

9.5, 7.5 Hz, 1H), 3.65-3.84 (m, 8H), 3.64 (s, 3H), 3.58-3.61

(m, 2H), 3.51 (dd, J ) 10.0, 6.0 Hz, 1H), 3.33 (dt, J ) 9.0, 7.0

Hz, 1H), 2.95 (s, 1H), 2.89 (t, J ) 6.5 Hz, 1H), 2.47-2.68 (m,

3H), 2.32-2.40 (m, 1H), 2.26 (t, J ) 7.5 Hz, 2H), 1.95 (s, 3H),

1.54-1.60 (m, 2H), 1.46-1.52 (m, 2H), 1.25-1.32 (m, 2H), 1.14

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

[2-O-ben zoyl-3-O-(2,3,4,6-tetr a -O-ben zyl-r-^D-ga la ctop yr a -

n osyl)-4-O-levu lin yl-6-O-ter t-b u t yld ip h en ylsilyl-â-^D-ga -

la c t o p y r a n o s y l]-4,6-O -p -m e t h o x y b e n z y li d e n e -â-^D-

glu cop yr a n osid e (31). This trisaccharide was prepared from

1a (17.4 mg, 0.0268 mmol), 2b (13.0 mg, 0.0179 mmol), and

6a (29.8 mg, 0.0537 mmol) as described in the preparation of

12, yielding product (17.1 mg, 57%) as a syrup: ¹H NMR (500

MHz, CDCl₃) δ 7.56 (dd, J ) 8.0, 1.5 Hz, 2H), 7.47 (dd, J )

8.0, 1.5 Hz, 2H), 7.18-7.42 (m, 31H), 7.14 (dd, J ) 8.0, 2.5

Hz, 2H), 7.05 (m, 2H), 6.99 (t, J ) 8.0 Hz, 2H), 6.79 (m, 2H),

5.62 (d, J ) 3.0 Hz, 1H), 5.37 (s, 1H), 5.23 (dd, J ) 10.5, 8.0

Hz, 1H), 5.18 (d, J ) 3.5 Hz, 1H), 5.07 (d, J ) 8.5 Hz, 1H),

4.86 (d, J ) 8.0 Hz, 1H), 4.74 (dd, J ) 10.5, 8.5 Hz, 1H), 4.64

(d, J ) 12.0 Hz, 1H), 4.62 (d, J ) 11.5 Hz, 1H), 4.52 (d, J )

12.0 Hz, 1H), 4.49 (d, J ) 12.0 Hz, 1H), 4.42 (d, J ) 12.0 Hz,

1H), 4.32 (dd, J ) 10.5, 5.0 Hz, 1H), 4.28 (d, J ) 5.0 Hz, 1H),

4.25 (dd, J ) 8.0, 1.5 Hz, 1H), 4.18 (d, J ) 10.5 Hz, 1H), 4.16

(d, J ) 10.5 Hz, 1H), 3.90 (dd, J ) 10.5, 3.0 Hz, 1H), 3.73-

3.82 (m, 3H), 3.68-3.72 (m, 4H), 3.56-3.64 (m, 8H), 3.35 (dd,

J ) 9.5, 7.5 Hz, 1H), 3.30 (dt, J ) 10.0, 6.5 Hz, 1H), 3.23 (dd,

J ) 10.0, 2.5 Hz, 1H), 2.97 (dd, J ) 9.5, 5.0 Hz, 1H), 2.82 (d,

J ) 1.5 Hz, 1H), 2.24-2.37 (m, 3H), 2.13-2.22 (m, 1H), 1.92

(s, 3H), 1.81-1.94 (m, 2H), 1.19-1.41 (m, 6H), 1.01 (s, 9H);

¹³C NMR (125 MHz, CDCl₃) δ 206.3, 173.8, 171.2, 164.1, 160.0,

138.8, 138.7, 138.3, 138.0, 135.8, 135.6, 133.5, 133.0, 132.6,

132.5, 129.8, 129.7, 129.5, 129.5, 129.0, 128.4, 128.2, 128.1,

128.0, 128.0, 127.8, 127.6, 127.4, 127.4, 127.2, 127.2, 126.9,

113.7, 100.8, 100.2, 98.6, 93.2, 81.50, 78.59, 75.91, 75.83, 74.48,

74.33, 73.25, 73.11, 73.07, 72.97, 71.51, 71.43, 69.45, 69.36,

69.01, 68.47, 66.29, 64.35, 61.14, 55.13, 55.00, 51.32, 37.96,

33.57, 29.51, 28.79, 28.10, 26.82, 25.15, 24.23, 19.01; HRMS

(M + Cs) calcd for C₉₇H₁₀₅O₂₃NSiCs 1812.5901, found 1812.5773.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

[2-O-b en zoyl-3-O-(2,3,4,6-t et r a -O-b en zyl-r-^D-glu cop yr a -

n osyl)-4-O-le vu lin yl-6-O-t er t -b u t yld ip h e n ylsilyl-â-^D-

ga la ctop yr a n osyl]-4,6-O-p-m eth oxyben zylid en e-â-^D-glu -

cop yr a n osid e (32). This trisaccharide was prepared from 1b

(80.1 mg, 0.1240 mmol), 2b (60.0 mg, 0.08264 mmol), and 6a

(137.6 mg, 0.2479 mmol) as described in the preparation of

12, yielding product (73.1 mg, 53%) as a syrup: ¹H NMR (500

MHz, CDCl₃) δ 7.58 (dd, J ) 8.0, 1.5 Hz, 2H), 7.48 (dd, J )

8.0, 1.5 Hz, 2H), 7.10-7.43 (m, 33H), 6.97 (t, J ) 8.0 Hz, 2H),

6.84 (d, J ) 9.0 Hz, 2H), 6.73 (dd, J ) 7.5, 1.5 Hz, 2H), 5.65

(d, J ) 3.0 Hz, 1H), 5.34 (s, 1H), 5.23 (dd, J ) 10.0, 8.0 Hz,

1H), 5.11 (d, J ) 3.5 Hz, 1H), 5.06 (d, J ) 8.5 Hz, 1H), 4.86 (d,

J ) 8.0 Hz, 1H), 4.65-4.71 (m, 3H), 4.53 (d, J ) 12.0 Hz, 1H),

4.44 (d, J ) 11.0 Hz, 1H), 4.42 (d, J ) 12.0 Hz, 1H), 4.40 (d,

J ) 11.0 Hz, 1H), 4.30 (dd, J ) 10.0, 5.0 Hz, 1H), 4.28 (d, J )

12.0 Hz, 1H), 4.24 (dd, J ) 10.0, 8.5 Hz, 1H), 4.05-4.08 (m,

1H), 3.88 (dd, J ) 10.5, 3.0 Hz, 1H), 3.76-3.82 (m, 2H), 3.74

(s, 3H), 3.61-3.73 (m, 3H), 3.52-3.59 (m, 5H), 3.40 (t, J ) 9.5

Hz, 1H), 3.28-3.35 (m, 4H), 3.24 (q, J ) 9.0 Hz, 1H), 3.16 (dd,

J ) 10.5, 4.0 Hz, 1H), 2.27-2.35 (m, 3H), 2.17-2.25 (m, 1H),

1.93 (s, 3H), 1.80-1.92 (m, 2H), 1.19-1.40 (m, 4H), 1.03 (s,

9H), 0.99-1.03 (m, 2H); ¹³C NMR (125 MHz, CDCl₃) δ 206.3,

173.8, 171.2, 164.4, 160.0, 138.6, 138.5, 138.4, 137.7, 135.8,

135.6, 133.5, 133.0, 132.5, 129.8, 129.7, 129.6, 129.3, 128.9,

128.3, 128.2, 128.1, 127.9, 127.8, 127.7, 127.7, 127.6, 127.4,

127.3, 127.1, 127.0, 113.7, 100.7, 100.1, 98.5, 93.3, 81.36, 81.31,

79.26, 77.09, 75.73, 75.31, 74.27, 73.31, 73.22, 73.13, 72.40,

71.10, 70.24, 69.42, 68.45, 67.84, 66.25, 64.43, 61.25, 55.15,

55.03, 51.32, 37.91, 33.56, 29.56, 28.78, 28.03, 26.84, 25.10,

24.22, 19.04; HRMS (M + Cs) calcd for C₉₇H₁₀₅O₂₃NSiCs

1812.5901, found 1812.6013.

(d, J ) 6.5 Hz, 3H), 1.07 (s, 9H), 0.95 (d, J ) 6.5 Hz, 3H); ¹³

C

NMR (125 MHz, CDCl₃) δ 206.4, 174.0, 171.9, 164.4, 139.4,

139.3, 138.9, 138.6, 138.3, 138.0, 135.5, 135.4, 133.6, 133.0,

132.9, 129.9, 129.8, 129.7, 129.4, 128.5, 128.4, 128.3, 128.2,

128.1, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5, 127.5, 127.3,

127.2, 127.0, 127.0, 126.2, 101.5, 100.9, 100.1, 98.9, 97.0, 80.00,

79.09, 78.79, 78.21, 77.45, 76.56, 75.77, 74.74, 74.70, 74.70,

73.91, 73.67, 73.61, 72.66, 72.34, 72.09, 72.09, 71.61, 69.67,

68.77, 68.45, 67.16, 66.23, 65.99, 61.83, 51.46, 38.01, 33.93,

29.68, 29.35, 28.40, 26.76, 25.63, 24.75, 19.31, 16.62, 16.42;

HRMS (M + Cs) calcd for C₁₀₈H₁₂₂O₂₄SiCs 1963.7150, found

1963.7267.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-[2-O-ben zoyl-3-O-(2,3,4,6-tetr a -O-ben zyl-r-^D-

ga la ctop yr a n osyl)-4-O-levu lin yl-6-O-ter t-bu tyld ip h en yl-

silyl-â-^D-ga la ct op yr a n osyl]-6-O-p -m e t h oxyb e n zyl-â-D-

glu cop yr a n osid e (33). This trisaccharide was prepared from

1a (66.7 mg, 0.1033 mmol), 2b (50.0 mg, 0.06887 mmol), and

6b (133.7 mg, 0.2066 mmol) as described in the preparation

of 12, yielding product (63.2 mg, 52%) as a syrup: ¹H NMR

(500 MHz, CDCl₃) δ 8.04 (dd, J ) 8.0, 1.0 Hz, 2H), 7.56-7.74

(m, 7H), 7.49 (t, J ) 7.5 Hz, 1H), 7.17-7.41 (m, 29H), 7.10-

One-Pot Oligosaccharide Synthesis

J . Org. Chem., Vol. 65, No. 8, 2000 2423

7.12 (m, 2H), 6.91-6.93 (m, 2H), 6.83 (d, J ) 8.5 Hz, 2H),

6.74-6.77 (m, 3H), 5.72 (d, J ) 3.0 Hz, 1H), 5.49 (dd, J ) 10.5,

8.0 Hz, 1H), 5.29 (d, J ) 3.0 Hz, 1H), 4.95 (d, J ) 8.5 Hz, 1H),

4.78 (d, J ) 8.0 Hz, 1H), 4.75 (d, J ) 12.5 Hz, 1H), 4.74 (d, J

) 11.5 Hz, 1H), 4.72 (d, J ) 12.0 Hz, 1H), 4.64 (d, J ) 12.0

Hz, 1H), 4.58 (d, J ) 12.0 Hz, 1H), 4.50 (d, J ) 11.5 Hz, 1H),

4.46 (d, J ) 12.0 Hz, 1H), 4.40 (d, J ) 12.0 Hz, 1H), 4.37 (d,

J ) 12.0 Hz, 1H), 4.33 (d, J ) 12.0 Hz, 1H), 4.31 (d, J ) 12.0

Hz, 1H), 4.29 (d, J ) 11.5 Hz, 1H), 4.22 (dd, J ) 10.5, 8.5 Hz,

1H), 4.03-4.08 (m, 2H), 3.99 (dd, J ) 10.0, 8.5 Hz, 1H), 3.93

(dd, J ) 10.0, 3.0 Hz, 1H), 3.91 (t, J ) 6.0 Hz, 1H), 3.73 (s,

3H), 3.63-3.69 (m, 3H), 3.45-3.59 (m, 8H), 3.35-3.38 (m, 1H),

3.21-3.28 (m, 3H), 2.21-2.45 (m, 4H), 1.88-1.96 (m, 2H), 1.86

(s, 3H), 1.25-1.39 (m, 4H), 1.03 (s, 9H), 0.98-1.03 (m, 2H);

¹³C NMR (125 MHz, CDCl₃) δ 206.0, 173.8, 171.2, 164.6, 159.1,

138.8, 138.6, 138.4, 138.3, 138.1, 135.6, 135.5, 133.6, 133.2,

133.0, 132.9, 130.2, 129.8, 129.7, 129.6, 129.3, 128.5, 128.3,

128.2, 128.1, 128.0, 127.8, 127.7, 127.6, 127.4, 127.4, 127.3,

127.2, 126.8, 113.6, 100.6, 98.1, 93.6, 78.73, 77.99, 77.20, 77.10,

75.70, 74.73, 74.70, 74.45, 73.42, 73.07, 73.02, 72.80, 72.12,

71.65, 69.71, 69.23, 68.99, 67.50, 64.70, 60.89, 55.60, 55.15,

51.27, 37.84, 33.61, 29.36, 28.76, 27.98, 26.74, 25.20, 24.28,

19.02; HRMS (M + Cs) calcd for C₁₀₄H₁₁₃O₂₃NSiCs 1904.6527,

found 1904.6796.

Hz, 2H), 3.57 (s, 3H), 3.53-3.56 (m, 2H), 3.39-3.44 (m, 2H),

3.24 (dt, J ) 9.8, 6.4 Hz, 2H), 2.39-2.66 (m, 4H), 1.95 (s, 3H),

1.85-1.93 (m, 2H), 1.27-1.39 (m, 4H), 1.21 (d, J ) 6.5 Hz,

3H), 1.03 (s, 9H), 0.98-1.02 (m, 2H); ¹³C NMR (100 MHz,

CDCl₃) δ 205.85, 173.83, 171.80, 164.28, 159.40, 138.87, 138.57,

138.54, 138.25, 135.60, 135.46, 133.60, 133.58, 133.26, 132.98,

132.79, 130.14, 129.79, 129.75, 129.62, 129.57, 129.42, 128.59,

128.31, 128.16, 128.09, 127.79, 127.77, 127.70, 127.65, 127.46,

127.32, 127.18, 126.93, 126.82, 113.78, 100.81, 98.63, 98.11,

78.71, 77.65, 77.46, 76.57, 74.78, 74.67, 74.50, 74.34, 73.58,

73.33, 72.98, 72.86, 72.60, 71.88, 69.02, 67.20, 67.10, 60.26,

55.52, 55.31, 51.30, 38.22, 33.63, 29.48, 28.75, 28.30, 26.72,

25.20, 24.29, 18.98, 16.51; HRMS (M + Cs) calcd for C₉₇H₁₀₇O₂₂-

NSiCs 1798.6108, found 1798.6230.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-p-m eth oxyben zyl-6-O-[2-O-ben zoyl-3-O-(2,3,4,6-

tetr a -O-ben zyl-r-^D-ga la ctop yr a n osyl)-4-O-levu lin yl-6-O-

t er t -b u t y ld i p h e n y ls i ly l-â-^D-g a la c t o p y r a n o s y l]-â-D -

glu cop yr a n osid e (36) a n d 5-Met h oxyca r b on ylp en t yl

2-Deoxy-2-ph th alim ido-3-O-ben zyl-4-O-p-m eth oxyben zyl-

6-O-[2-O-ben zoyl-3-O-(2,3,4,6-tetr a -O-ben zyl-r-^D-ga la cto-

p yr a n osyl)-4-O-levu lin yl-6-O-ter t-bu tyld ip h en ylsilyl-r-^D-

ga la ctop yr a n osyl]-â-^D-glu cop yr a n osid e (37). These two

trisaccharides were prepared from 1a (66.7 mg, 0.1033 mmol),

2b (50.0 mg, 0.06887 mmol), and 6c (133.7 mg, 0.2066 mmol)

as described in the preparation of 12, yielding 36 (75.0 mg,

61%) as a syrup and 37 (10.5 mg, 9%) as a syrup. For

compound 36: ¹H NMR (500 MHz, CDCl₃) δ 7.95 (d, J ) 7.5

Hz, 2H), 7.57-7.75 (m, 8H), 7.19-7.43 (m, 25H), 7.08-7.11

(m, 4H), 7.03 (d, J ) 8.5 Hz, 2H), 6.93 (d, J ) 7.5 Hz, 2H),

6.79-6.87 (m, 3H), 6.72 (d, J ) 8.5 Hz, 2H), 5.66(d, J ) 3.0

Hz, 1H), 5.56 (dd, J ) 10.5, 8.5 Hz, 1H), 5.26 (d, J ) 3.5 Hz,

1H), 4.95 (d, J ) 8.5 Hz, 1H), 4.71 (d, J ) 11.5 Hz, 1H), 4.68

(d, J ) 5.5 Hz, 1H), 4.65 (d, J ) 11.5 Hz, 1H), 4.61 (d, J ) 8.0

Hz, 1H), 4.55 (d, J ) 12.0 Hz, 1H), 4.52 (d, J ) 12.0 Hz, 1H),

4.43 (ABq, J ) 10.5 Hz, 2H), 4.36 (d, J ) 12.0 Hz, 1H), 4.32

(d, J ) 12.0 Hz, 1H), 4.31 (d, J ) 12.0 Hz, 1H), 4.27 (d, J )

11.5 Hz, 1H), 4.19-4.23 (m, 2H), 4.02-4.09 (m, 2H), 3.88-

3.92 (m, 2H), 3.73-3.81 (m, 2H), 3.72 (s, 3H), 3.65-3.71 (m,

2H), 3.58-3.63 (m, 2H), 3.57 (s, 3H), 3.52 (dd, J ) 10.5, 3.0

Hz, 1H), 3.38-3.48 (m, 3H), 3.16-3.22 (m, 2H), 3.00-3.04 (m,

1H), 2.32-2.47 (m, 4H), 1.98 (s, 3H), 1.75-1.87 (m, 2H), 1.16-

1.27 (m, 4H), 1.05 (s, 9H), 1.02-1.09 (m, 2H); ¹³C NMR (100

MHz, CDCl₃) δ 206.33, 173.77, 171.56, 164.57, 159.15, 138.77,

138.60, 138.31, 138.17, 137.92, 135.58, 135.51, 133.61, 133.24,

132.93, 132.92, 129.85, 129.77, 129.75, 129.66, 129.40, 128.34,

128.27, 128.20, 128.12, 128.07, 127.92, 127.77, 127.73, 127.69,

127.62, 127.55, 127.47, 127.29, 127.25, 127.17, 113.65, 101.13,

97.85, 93.40, 79.38, 79.13, 78.75, 75.70, 74.64, 74.56, 74.42,

74.40, 74.24, 73.90, 73.36, 73.08, 73.00, 71.93, 70.62, 69.70,

69.39, 68.74, 67.82, 64.94, 61.74, 55.74, 55.16, 51.30, 37.94,

33.58, 29.55, 28.54, 28.14, 26.70, 25.16, 24.26, 19.08; HRMS

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-[2-O-ben zoyl-3-O-(2,3,4,6-tetr a -O-ben zyl-r-^D-

glu copyr an osyl)-4-O-levu lin yl-6-O-ter t-bu tyldiph en ylsilyl-

â-^D-g a l a c t o p y r a n o s y l ]-6 -O -p -m e t h o x y b e n z y l -â-D -

glu cop yr a n osid e (34). This trisaccharide was prepared from

1b (66.7 mg, 0.1033 mmol), 2b (50.0 mg, 0.06887 mmol), and

6b (113.7 mg, 0.2066 mmol) as described in the preparation

of 12, yielding product (70.1 mg, 57%) as a thick oil: ¹H NMR

(500 MHz, CDCl₃) δ 8.00 (d, J ) 7.0 Hz, 2H), 7.58-7.74 (m,

8H), 7.19-7.42 (m, 27H), 7.14-7.17 (m, 2H), 6.91-6.94 (m,

2H), 6.86 (d, J ) 8.5 Hz, 2H), 6.74-6.79 (m, 5H), 5.74 (d, J )

3.0 Hz, 1H), 5.49 (dd, J ) 10.5, 8.5 Hz, 1H), 5.21 (d, J ) 3.0

Hz, 1H), 4.94 (d, J ) 8.5 Hz, 1H), 4.79 (d, J ) 10.5 Hz, 1H),

4.75 (d, J ) 12.5 Hz, 1H), 4.74 (d, J ) 8.5 Hz, 1H), 4.73 (d, J

) 11.0 Hz, 1H), 4.62 (d, J ) 12.5 Hz, 1H), 4.57 (d, J ) 11.0

Hz, 1H), 4.54 (d, J ) 10.5 Hz, 1H), 4.52 (d, J ) 11.5 Hz, 1H),

4.49 (d, J ) 12.5 Hz, 1H), 4.40 (d, J ) 12.0 Hz, 1H), 4.38 (d,

J ) 12.0 Hz, 1H), 4.30 (d, J ) 11.5 Hz, 1H), 4.22 (d, J ) 11.5

Hz, 1H), 4.20 (dd, J ) 10.5, 8.5 Hz, 1H), 3.97-4.08 (m, 3H),

3.75 (s, 3H), 3.61-3.70 (m, 5H), 3.56 (s, 3H), 3.48-3.59 (m,

4H), 3.44 (dd, J ) 9.5, 3.0 Hz, 1H), 3.40 (d, J ) 9.5 Hz, 1H),

3.32-3.38 (m, 2H), 3.25 (dt, J ) 9.5, 6.5 Hz, 1H), 2.28-2.42

(m, 3H), 2.19-2.27 (m, 1H), 1.87-1.98 (m, 2H), 1.84 (s, 3H),

1.24-1.42 (m, 4H), 1.05 (s, 9H), 0.96-1.05 (m, 2H); ¹³C NMR

(125 MHz, CDCl₃) δ 205.9, 173.8, 171.2, 164.7, 159.2, 138.6,

138.6, 138.5, 137.8, 135.6, 135.5, 133.6, 133.1, 133.1, 132.9,

130.3, 129.7, 129.4, 129.3, 128.3, 128.2, 127.9, 127.9, 127.8,

127.7, 127.7, 127.3, 127.1, 126.9, 113.7, 100.6, 98.1, 93.7, 81.37,

79.31, 77.73, 77.35, 76.96, 75.41, 74.68, 74.41, 74.28, 73.51,

73.42, 73.13, 72.97, 72.90, 71.52, 70.67, 69.02, 68.24, 67.47,

64.89, 60.98, 55.60, 55.20, 51.30, 37.83, 33.60, 29.39, 28.79,

27.95, 26.79, 25.26, 24.31, 19.07; HRMS (M + Cs) calcd for

(M + Cs) calcd for

C₁₀₄H₁₁₃O₂₃NSiCs 1904.6527, found

1904.6670. For compound 37: ¹H NMR (400 MHz, CDCl₃) δ

8.14 (d, J ) 7.3 Hz, 2H), 6.99-7.79 (m, 39H), 6.79-6.93 (m,

7H), 5.66 (d, J ) 3.0 Hz, 1H), 5.47 (dd, J ) 10.5, 3.6 Hz, 1H),

5.41 (d, J ) 3.6 Hz, 1H), 5.24 (d, J ) 3.4 Hz, 1H), 4.94 (d, J )

8.5 Hz, 1H), 4.76 (d, J ) 11.2 Hz, 1H), 4.60-4.72 (m, 4H), 4.59

(d, J ) 11.7 Hz, 1H), 4.49 (dd, J ) 10.5, 3.2 Hz, 1H), 4.45 (d,

J ) 11.7 Hz, 1H), 4.40 (d, J ) 11.9 Hz, 1H), 4.33 (d, J ) 12.0

Hz, 1H), 4.32 (d, J ) 11.3 Hz, 1H), 4.28 (d, J ) 12.3 Hz, 1H),

4.26 (dd, J ) 10.5, 8.5 Hz, 1H), 4.18 (t, J ) 6.5 Hz, 1H), 4.08

(t, J ) 6.5 Hz, 1H), 3.96 (dd, J ) 10.0, 3.2 Hz, 1H), 3.41-3.93

(m, 19H), 3.14 (dt, J ) 9.8, 6.5 Hz, 1H), 2.29-2.50 (m, 4H),

1.94 (s, 3H), 1.82-1.93 (m, 2H), 1.12-1.25 (m, 4H), 1.05 (s,

C

₁₀₄H₁₁₃O₂₃NSiCs 1904.6527, found 1904.6680.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

b en zyl-4-O-[2-O-b en zoyl-3-O-(2,3,4-t r i-O-b en zyl-r-^L-fu -

cop yr a n osyl)-4-O-levu lin yl-6-O-ter t-bu tyld ip h en ylsilyl-

â-^D-g a l a c t o p y r a n o s y l ]-6 -O -p -m e t h o x y b e n z y l -â-D -

glu cop yr a n osid e (35). This trisaccharide was prepared from

1c (55.8 mg, 0.1033 mmol), 2b (50.0 mg, 0.06887 mmol), and

6b (113.7 mg, 0.2066 mmol) as described in the preparation

of 12, yielding product (71.6 mg, 62%) as a thick oil: ¹H NMR

(400 MHz, CDCl₃) δ 7.89 (dd, J ) 8.2, 1.2 Hz, 2H), 7.54-7.75

(m, 8H), 7.33-7.44 (m, 8H), 7.20-7.30 (m, 13H), 7.09-7.16

(m, 3H), 6.91-6.97 (m, 6H), 6.74-6.78 (m, 3H), 5.54 (d, J )

3.2 Hz, 1H), 5.49 (dd, J ) 10.1, 8.0 Hz, 1H), 5.11 (d, J ) 3.2

Hz, 1H), 4.93 (d, J ) 8.4 Hz, 1H), 4.90 (d, J ) 11.5 Hz, 1H),

4.76 (d, J ) 12.2 Hz, 1H), 4.68 (ABq, J ) 11.9 Hz, 2H), 4.62

(d, J ) 12.0 Hz, 1H), 4.60 (d, J ) 7.4 Hz, 1H), 4.59 (d, J )

11.7 Hz, 1H), 4.41 (d, J ) 12.1 Hz, 1H), 4.24-4.31 (m, 2H),

4.11-4.20 (m, 3H), 4.02-4.09 (m, 3H), 3.99 (dd, J ) 9.8, 8.7

Hz, 1H), 3.78-3.86 (m, 2H), 3.75 (s, 3H), 3.66 (dt, J ) 9.8, 6.0

9H), 0.98-1.03 (m, 2H); HRMS (M + Cs) calcd for C₁₀₄H₁₁₃O₂₃

NSiCs 1904.6527, found 1904.6678.

-

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-p-m eth oxyben zyl-6-O-[2-O-ben zoyl-3-O-(2,3,4,6-

t et r a -O-b en zyl-r-^D-glu cop yr a n osyl)-4-O-levu lin yl-6-O-

t er t -b u t y ld i p h e n y ls i ly l-â-^D-g a la c t o p y r a n o s y l]-â-D -

glu cop yr a n osid e (38). This trisaccharide was prepared from

1b (66.7 mg, 0.1033 mmol), 2b (50.0 mg, 0.06887 mmol), and

6c (133.7 mg, 0.2066 mmol) as described in the preparation

of 12, yielding product (63.6 mg, 52%) as a syrup: ¹H NMR

2424 J . Org. Chem., Vol. 65, No. 8, 2000

Ye and Wong

(500 MHz, CDCl₃) δ 7.91 (d, J ) 8.0 Hz, 2H), 7.13-7.76 (m,

33H), 7.08 (t, J ) 7.5 Hz, 2H), 7.03 (d, J ) 9.0 Hz, 2H), 6.93

(d, J ) 7.5 Hz, 2H), 6.80-6.88 (m, 3H), 6.77 (d, J ) 7.0 Hz,

2H), 6.73 (d, J ) 8.5 Hz, 2H), 5.70 (d, J ) 3.0 Hz, 1H), 5.55

(dd, J ) 10.0, 8.0 Hz, 1H), 5.20 (d, J ) 3.0 Hz, 1H), 4.93 (d, J

) 8.5 Hz, 1H), 4.79 (d, J ) 11.0 Hz, 1H), 4.71 (d, J ) 12.0 Hz,

1H), 4.67 (d, J ) 12.0 Hz, 1H), 4.64 (d, J ) 8.0 Hz, 1H), 4.61

(d, J ) 11.5 Hz, 1H), 4.56 (d, J ) 11.0 Hz, 1H), 4.53 (d, J )

11.5 Hz, 1H), 4.48 (d, J ) 12.0 Hz, 1H), 4.46 (d, J ) 10.5 Hz,

1H), 4.38 (d, J ) 12.0 Hz, 1H), 4.36 (d, J ) 12.5 Hz, 1H), 4.32

(d, J ) 12.0 Hz, 1H), 4.17-4.22 (m, 3H), 4.05 (dd, J ) 10.5,

3.5 Hz, 1H), 4.03 (dd, J ) 11.0, 8.5 Hz, 1H), 3.76 (dd, J ) 12.5,

3.5 Hz, 1H), 3.73 (s, 3H), 3.72 (dd, J ) 6.5, 3.5 Hz, 1H), 3.68

(d, J ) 9.0 Hz, 1H), 3.67 (d, J ) 9.0 Hz, 1H), 3.61 (dd, J )

10.5, 6.5 Hz, 1H), 3.58 (s, 3H), 3.56 (dd, J ) 11.0, 6.5 Hz, 1H),

3.33-3.45 (m, 7H), 2.99 (m, 1H), 2.34-2.45 (m, 4H), 1.98 (s,

3H), 1.75-1.86 (m, 2H), 1.18-1.35 (m, 4H), 1.06 (s, 9H), 0.98-

1.05 (m, 2H); ¹³C NMR (125 MHz, CDCl₃) δ 206.2, 173.7, 171.5,

164.9, 159.2, 138.6, 138.5, 138.4, 137.9, 137.8, 135.6, 135.5,

133.6, 133.2, 132.9, 132.8, 129.8, 129.8, 129.7, 129.6, 129.5,

129.4, 128.3, 128.2, 128.1, 127.9, 127.9, 127.8, 127.8, 127.7,

127.7, 127.6, 127.4, 127.4, 127.3, 127.2, 127.1, 123.2, 113.7,

101.3, 97.8, 93.5, 81.34, 79.42, 79.32, 79.13, 77.32, 75.38, 74.53,

74.47, 74.43, 74.27, 73.97, 73.36, 73.10, 72.84, 70.56, 68.70,

68.20, 67.76, 65.14, 61.75, 55.72, 55.16, 51.28, 37.90, 33.57,

29.63, 29.56, 28.59, 28.09, 26.72, 25.18, 24.26, 19.09; HRMS

4.26 (m, 3H), 4.06 (dd, J ) 11.0, 8.5 Hz, 1H), 4.00 (dd, J )

10.0, 3.5 Hz, 1H), 3.86-3.94 (m, 2H), 3.75 (s, 3H), 3.69-3.74

(m, 3H), 3.64 (q, J ) 7.0 Hz, 1H), 3.58 (s, 3H), 3.50-3.57 (m,

2H), 3.43-3.64 (m, 2H), 3.02-3.07 (m, 1H), 2.14-2.33 (m, 4H),

1.83 (s, 3H), 1.78-1.90 (m, 2H), 1.18-1.30 (m, 4H), 1.06 (s,

9H), 1.01-1.04 (m, 2H), 0.81 (d, J ) 6.5 Hz, 3H); ¹³C NMR

(125 MHz, CDCl₃) δ 205.7, 173.8, 172.2, 164.9, 159.2, 139.0,

138.8, 138.6, 138.0, 135.6, 135.5, 133.6, 133.2, 133.2, 132.9,

130.0, 129.8, 129.8, 129.3, 128.4, 128.3, 128.3, 128.2, 128.1,

128.0, 127.8, 127.6, 127.5, 127.3, 127.2, 123.0, 113.7, 101.7,

98.0, 97.7, 79.55, 79.21, 78.81, 77.55, 76.34, 75.72, 74.75, 74.69,

74.56, 74.46, 74.13, 73.29, 72.99, 71.83, 69.81, 68.93, 67.64,

67.20, 63.32, 55.81, 55.22, 51.32, 37.61, 33.66, 29.68, 28.67,

27.86, 26.84, 25.28, 24.35, 19.20, 16.44; HRMS (M + Cs) calcd

for C₉₇H₁₀₇O₂₂NSiCs 1798.6108, found 1798.6256.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

[2-O-ben zoyl-3-O-p-m eth oxyben zyl-4-O-(2,3,4-tr i-O-ben -

zyl-r-^L-fu cop yr a n osyl)-6-O-ter t-b u t yld ip h en ylsilyl-â-D-

ga la ct op yr a n osyl]-4,6-O-p -m e t h oxyb e n zylid e n e -â-^D-

glu cop yr a n osid e (41). This trisaccharide was prepared from

1c (72.2 mg, 0.1337 mmol), 2c (50.0 mg, 0.06684 mmol), and

6a (111.3 mg, 0.2005 mmol) as described in the preparation

of 12, yielding product (36.2 mg, 34%) as a syrup: ¹H NMR

(500 MHz, CDCl₃) δ 7.51-7.61 (m, 8H), 7.46 (d, J ) 8.5 Hz,

2H), 7.01-7.39 (m, 26H), 6.82 (d, J ) 8.5 Hz, 2H), 6.77 (d, J

) 8.5 Hz, 2H), 6.53 (d, J ) 9.0 Hz, 2H), 5.56 (d, J ) 3.5 Hz,

1H), 5.53 (s, 1H), 5.47 (dd, J ) 10.0, 7.5 Hz, 1H), 5.08 (d, J )

8.5 Hz, 1H), 4.84 (d, J ) 8.0 Hz, 1H), 4.82 (d, J ) 12.0 Hz,

2H), 4.76 (dd, J ) 10.0, 8.5 Hz, 1H), 4.71 (d, J ) 13.0 Hz, 1H),

4.55 (d, J ) 11.5 Hz, 1H), 4.52 (d, J ) 11.5 Hz. 1H), 4.40 (d,

J ) 11.5 Hz, 1H), 4.38 (d, J ) 12.5 Hz, 1H), 4.30 (dd, J )

10.5, 8.5 Hz, 1H), 4.30 (dd, J ) 10.5, 5.5 Hz, 1H), 4.23 (d, J )

11.5 Hz, 1H), 4.17 (d, J ) 1.5 Hz, 1H), 3.86-3.90 (m, 2H), 3.83

(dd, J ) 10.0, 3.5 Hz, 1H), 3.73-3.80 (m, 3H), 3.72 (s, 3H),

3.68 (s, 3H), 3.61 (dd, J ) 10.5, 2.5 Hz, 1H), 3.58 (s, 3H), 3.56

(dd, J ) 10.0, 5.0 Hz, 1H), 3.49-3.52 (m, 2H), 3.42 (q, J ) 6.5

Hz, 1H), 3.30 (dt, J ) 9.5, 6.5 Hz, 1H), 3.22 (d, J ) 2.0 Hz,

1H), 1.83-1.96 (m, 2H), 1.22-1.37 (m, 4H), 1.04 (s, 9H), 0.95-

1.02 (m, 2H), 0.77 (d, J ) 6.5 Hz, 3H); ¹³C NMR (125 MHz,

CDCl₃) δ 173.8, 164.5, 159.8, 159.1, 139.5, 139.0, 138.7, 135.6,

135.5, 133.5, 133.1, 132.4, 131.3, 130.2, 130.1, 129.8, 129.8,

129.7, 129.4, 129.3, 128.6, 128.2, 128.1, 128.0, 128.0, 127.8,

127.8, 127.6, 127.4, 127.3, 127.2, 127.0, 126.7, 113.5, 113.4,

100.5, 100.3, 98.8, 96.1, 80.98, 80.23, 78.52, 75.26, 74.94, 74.77,

74.35, 73.47, 72.71, 71.57, 71.31, 69.43, 68.49, 67.83, 66.66,

66.48, 64.06, 55.60, 55.16, 55.08, 51.32, 33.62, 29.66, 28.86,

27.07, 25.20, 24.28, 19.19, 16.65; HRMS (M + Cs) calcd for

(M + Cs) calcd for

1904.6654.

C₁₀₄H₁₁₃O₂₃NSiCs 1904.6527, found

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-p-m eth oxyben zyl-6-O-[2-O-ben zoyl-3-O-(2,3,4-

t r i-O-b en zyl-r-^L-fu cop yr a n osyl)-4-O-levu lin yl-6-O-ter t-

b u t y l d i p h e n y l s i l y l -â-^D-g a l a c t o p y r a n o s y l ] -â-D -

glu cop yr a n osid e (39) a n d 5-Met h oxyca r b on ylp en t yl

2-d eoxy-2-p h th a lim id o-3-O-ben zyl-4-O-p-m eth oxyben zyl-

6-O-[2-O-ben zoyl-3-O-(2,3,4-tr i-O-ben zyl-â-^L-fu cop yr a n o-

syl)-4-O-levu lin yl-6-O-ter t-bu tyld ip h en ylsilyl-r-^D-ga la c-

topyranosyl]-â-^D-glucopyranoside (40).Thesetwotrisaccharides

were prepared from 1c (55.8 mg, 0.1033 mmol), 2b (50.0 mg,

0.06887 mmol), and 6c (133.7 mg, 0.2066 mmol) as described

in the preparation of 12, yielding 39 (71.4 mg, 62%) as a syrup

and 40 (22.2 mg, 19%) as a syrup. For compound 39: ¹H NMR

(500 MHz, CDCl₃) δ 7.90 (d, J ) 7.5 Hz, 2H), 7.10-7.75 (m,

30H), 7.03 (d, J ) 8.5 Hz, 2H), 6.95 (d, J ) 7.0 Hz, 2H), 6.94

(d, J ) 7.0 Hz, 2H), 6.81-6.88 (m, 3H), 6.74 (d, J ) 8.5 Hz,

2H), 5.57 (dd, J ) 10.0, 8.5 Hz, 1H), 5.55 (d, J ) 3.5 Hz, 1H),

5.15 (d, J ) 3.5 Hz, 1H), 4.91 (d, J ) 8.5 Hz, 1H), 4.89 (d, J )

11.5 Hz, 1H), 4.71 (d, J ) 12.0 Hz, 1H), 4.68 (d, J ) 12.0 Hz,

1H), 4.66 (d, J ) 12.0 Hz, 1H), 4.63 (d, J ) 8.0 Hz, 1H), 4.59

(d, J ) 11.5 Hz, 1H), 4.46 (d, J ) 11.0 Hz, 1H), 4.36 (d, J )

10.5 Hz, 1H), 4.32 (d, J ) 12.0 Hz, 1H), 4.14-4.23 (m, 5H),

4.11 (d, J ) 12.0 Hz, 1H), 4.01-4.08 (m, 1H), 3.75-3.85 (m,

4H), 3.73 (s, 3H), 3.69-3.72 (m, 2H), 3.60 (dd, J ) 11.0, 6.5

Hz, 1H), 3.57 (s, 3H), 3.52-3.56 (m, 1H), 3.37-3.45 (m, 2H),

3.00-3.04 (m, 1H), 2.70 (t, J ) 7.0 Hz, 2H), 2.49-2.61 (m, 2H),

2.02 (s, 3H), 1.80-1.91 (m, 2H), 1.21-1.31 (m, 4H), 1.16 (d, J

) 6.5 Hz, 3H), 1.05 (s, 9H), 0.99-1.04 (m, 2H); ¹³C NMR (125

MHz, CDCl₃) δ 206.1, 173.7, 171.9, 164.4, 159.2, 138.9, 138.5,

138.2, 137.9, 135.6, 135.5, 133.6, 133.1, 133.0, 132.8, 129.8,

129.7, 129.7, 129.6, 129.3, 128.4, 128.1, 128.1, 127.9, 127.8,

127.5, 127.5, 127.4, 127.2, 127.2, 126.9, 123.0, 113.6, 101.5,

98.5, 97.9, 79.33, 79.13, 78.59, 77.41, 74.98, 74.68, 74.57, 74.47,

74.35, 73.85, 73.61, 72.67, 72.30, 71.81, 69.18, 68.74, 67.72,

67.19, 61.08, 55.68, 55.10, 51.26, 38.27, 33.57, 29.56, 28.62,

28.45, 26.65, 25.28, 24.32, 19.00, 16.48; HRMS (M + Cs) calcd

for C₉₇H₁₀₇O₂₂NSiCs 1798.6108, found 1798.6261. For com-

pound 40: ¹H NMR (500 MHz, CDCl₃) δ 7.96 (dd, J ) 8.5, 1.0

Hz, 2H), 7.24-7.76 (m, 30H), 7.20 (t, J ) 7.5 Hz, 2H), 7.04 (d,

J ) 8.5 Hz, 2H), 6.94 (d, J ) 7.0 Hz, 2H), 6.81-6.89 (m, 3H),

6.75 (d, J ) 8.5 Hz, 2H), 5.78 (dd, J ) 10.5, 8.0 Hz, 1H), 5.24

(d, J ) 3.5 Hz, 1H), 5.14 (dd, J ) 10.5, 2.5 Hz, 1H), 4.94 (d, J

) 8.5 Hz, 1H), 4.91 (d, J ) 11.5 Hz, 1H), 4.83 (d, J ) 11.5 Hz,

1H), 4.81 (d, J ) 12.0 Hz, 1H), 4.75 (d, J ) 13.0 Hz, 1H), 4.72

(d, J ) 8.0 Hz, 1H), 4.69 (d, J ) 11.5 Hz, 1H), 4.67 (d, J )

12.0 Hz, 1H), 4.58 (d, J ) 11.5 Hz, 1H), 4.44 (d, J ) 10.5 Hz,

1H), 4.38 (d, J ) 10.5 Hz, 1H), 4.33 (d, J ) 12.5 Hz, 1H), 4.20-

C

₉₃H₁₀₁O₂₁NSiCs 1728.5690, found 1728.5598.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-[2-O-ben zoyl-3-O-(2,3,4,6-tetr a -O-ben zyl-r-^D-

glu cop yr a n osyl)-4-O-levu lin yl-6-O-(2,3,4-tr i-O-ben zyl-^L-

f u c o p y r a n o s y l ) -â-^D-g a l a c t o p y r a n o s y l ] -6 -O -p -

m et h oxyb en zyl-â-^D-glu cop yr a n osid e (42). This tetra-

saccharide was prepared from 1c (21.4 mg, 0.0396 mmol), 2g

(20.0 mg, 0.0198 mmol), and 6b (38.4 mg, 0.0594 mmol) as

described in the preparation of 12, yielding product (29.3 mg,

76%) as a syrup: ¹H NMR (400 MHz, CDCl₃) δ 6.78-8.21 (m,

53H), 3.23-5.64 (m, 52H), 2.31-2.42 (m, 4H), 1.90-1.97 (m,

2H), 1.87 (s, 3H), 1.15-1.25 (m, 4H), 1.06 (d, J ) 6.5 Hz, 3H),

0.93-1.01 (m, 2H); HRMS (M + Cs) calcd for C₁₁₅H₁₂₃O₂₇NCs

2082.7337, found 2082.7462.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-6-O-[2-O-(2,3,4-O-ben zyl-r-^L-fu cop yr a n osyl)-3-O-

(2,3,4,6-t et r a -O-b en zyl-r-^D-ga la ct op yr a n osyl)-4-O-levu -

lin yl-6-O-ter t-bu tyldiph en ylsilyl-^D-galactopyr an osyl]-â-D-

glu cop yr a n osid e (43). This tetrasaccharide was prepared

from 1a (19.6 mg, 0.03035 mmol), 2f (21.0 mg, 0.02023 mmol),

and 6c (39.3 mg, 0.06069 mmol) as described in the prepara-

tion of 12, yielding product (22.9 mg, 58%) as a syrup: ¹H NMR

(400 MHz, CDCl₃) δ 6.83-7.86 (m, 54H), 3.24-5.73 (m, 48H),

2.25-2.43 (m, 3H), 2.05 (s, 3H), 1.91-2.02 (m, 3H), 1.25-1.39

(m, 4H), 1.18 (d, J ) 6.5 Hz, 3H), 1.06 (s, 9H), 0.96-1.01 (m,

2H); ESI-MS (pos) (M + H) calcd for C₁₁₆H₁₂₉O₂₅NSiH 1965,

found 1965.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

One-Pot Oligosaccharide Synthesis

J . Org. Chem., Vol. 65, No. 8, 2000 2425

ben zyl-4-O-[2-O-ben zoyl-3-O-(2,3,4,6-tetr a -O-ben zyl-r-D-

ga la ct op yr a n osyl)-4-O-(2,3,4-t r i-O-b en zyl-r-^L-fu cop yr a -

n osyl)-6-O-ter t-bu tyld ip h en ylsilyl-â-^D-ga la ctop yr a n osyl]-

6-O-p-m eth oxyben zyl-â-^D-glu cop yr a n osid e (44) This tetra-

saccharide was prepared from 1a (13.9 mg, 0.02155 mmol),

2e (15.0 mg, 0.01437 mmol), and 6b (27.9 mg, 0.04311 mmol)

as described in the preparation of 28, yielding product (17.2

mg, 57%) as a syrup: ¹H NMR (500 MHz, CDCl₃) δ 8.00 (d, J

) 8.0 Hz, 2H), 7.08-7.77 (m, 46H), 6.96-6.97 (m, 4H), 6.81-

6.85 (m, 6H), 6.76 (d, J ) 6.0 Hz, 2H), 6.64 (t, J ) 7.5 Hz,

1H), 6.55 (t, J ) 7.5 Hz, 2H), 5.98 (d, J ) 3.5 Hz, 1H), 5.90

(dd, J ) 10.0, 7.5 Hz, 1H), 5.28 (d, J ) 3.5 Hz, 1H), 4.94 (d, J

) 8.0 Hz, 1H), 4.88 (d, J ) 12.5 Hz, 1H), 4.83 (d, J ) 7.5 Hz,

1H), 4.81 (d, J ) 11.5 Hz, 1H), 4.78 (d, J ) 11.5 Hz, 1H), 4.64-

4.71 (m, 2H), 4.59 (d, J ) 11.0 Hz, 1H), 4.55 (d, J ) 12.5 Hz,

1H), 4.54 (d, J ) 12.0 Hz, 1H), 4.45 (d, J ) 11.0 Hz, 2H), 4.43

(d, J ) 12.0 Hz, 1H), 4.27-4.36 (m, 6H), 4.17 (d, J ) 12.0 Hz,

1H), 3.98-4.09 (m, 5H), 3.93 (d, J ) 12.0 Hz, 1H), 3.85-3.90

(m, 2H), 3.73-3.80 (m, 5H), 3.57-3.68 (m, 5H), 3.56 (s, 3H),

3.51 (q, J ) 6.5 Hz, 1H), 3.36-3.42 (m, 3H), 3.19-3.27 (m,

4H), 1.84-1.96 (m, 2H), 1.25-1.35 (m, 4H), 1.10 (s, 9H), 0.95-

1.03 (m, 2H), 0.90 (d, J ) 6.5 Hz, 3H); ¹³CNMR (100 MHz,

CDCl₃) δ 164.43, 159.11, 139.45, 139.42, 139.17, 138.78, 138.66,

138.51, 138.17, 137.88, 135.69, 135.48, 133.53, 133.47, 133.00,

130.40, 129.82, 129.74, 129.33, 128.70, 128.53, 128.45, 128.38,

128.33, 128.24, 128.19, 128.15, 128.00, 127.87, 127.74, 127.69,

127.66, 127.51, 127.48, 127.22, 126.84, 126.58, 113.71, 100.44,

98.15, 94.78, 94.29, 78.72, 78.28, 77.22, 77.17, 76.51, 75.59,

74.97, 74.83, 74.69, 74.65, 74.50, 74.22, 73.44, 73.34, 73.03,

72.84, 72.07, 71.46, 69.75, 69.06, 68.97, 67.90, 66.64, 64.92,

63.76, 55.74, 55.24, 51.35, 33.69, 29.70, 28.83, 27.02, 25.27,

24.37, 22.69, 19.25, 16.84, 14.13; HRMS (M + Cs) calcd for

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-[2-O-ben zoyl-3-O-p-m eth oxyben zyl-4-O-(2,3,4-

tr i-O-ben zyl-r-^L-fu cop yr a n osyl)-6-O-ter t-bu tyld ip h en yl-

silyl-â-^D-ga la ct op yr a n osyl]-6-O-p -m e t h oxyb e n zyl-â-D-

glu cop yr a n osid e (47). This trisaccharide was prepared from

1c (54.1 mg, 0.1003 mmol), 2c (50.0 mg, 0.06684 mmol), and

6b (129.7 mg, 0.2005 mmol) as described in the preparation

of 12, yielding product (80.0 mg, 71%) as a syrup: ¹H NMR

(500 MHz, CDCl₃) δ 8.01 (d, J ) 7.5 Hz, 2H), 7.54-7.78 (m,

10H), 7.49 (t, J ) 7.5 Hz, 2H), 7.12-7.74 (m, 20H), 7.04 (d, J

) 8.5 Hz, 2H), 6.87-6.90 (m, 6H), 6.67-6.72 (m, 3H), 6.62 (t,

J ) 7.5 Hz, 2H), 5.79 (dd, J ) 10.0, 7.5 Hz, 1H), 5.70 (d, J )

4.0 Hz, 1H), 4.96 (d, J ) 8.0 Hz, 1H), 4.87 (d, J ) 12.5 Hz,

1H), 4.81 (d, J ) 11.5 Hz, 1H), 4.72 (d, J ) 13.0 Hz, 1H), 4.61

(d, J ) 8.0 Hz, 1H), 4.60 (d, J ) 11.5 Hz, 1H), 4.55 (d, J )

11.5 Hz, 1H), 4.50 (d, J ) 11.5 Hz, 1H), 4.45 (d, J ) 12.0 Hz,

1H), 4.39 (d, J ) 11.5 Hz, 2H), 4.28 (d, J ) 11.5 Hz, 2H), 4.02-

4.09 (m, 4H), 3.85-3.89 (m, 2H), 3.78 (dd, J ) 10.5, 4.0 Hz,

1H), 3.75 (s, 3H), 3.73 (s, 3H), 3.67 (dt, J ) 9.5, 6.5 Hz, 1H),

3.54-3.64 (m, 3H), 3.56 (s, 3H), 3.44-3,51 (m, 4H), 3.32-3.34

(m, 1H), 3.23-3.27 (m, 2H), 1.86-1.97 (m, 2H), 1.28-1.38 (m,

4H), 1.11 (s, 9H), 0.97-1.02 (m, 2H), 0.81 (d, J ) 6.5 Hz, 3H);

¹³C NMR (125 MHz, CDCl₃) δ 173.8, 167.7, 167.5, 164.6, 159.2,

139.2, 139.1, 138.9, 138.6, 135.7, 135.4, 133.6, 133.5, 133.4,

133.1, 132.9, 130.4, 130.2, 129.9, 129.7, 129.7, 129.5, 129.4,

128.5, 128.5, 128.4, 128.3, 128.0, 127.9, 127.8, 127.7, 127.6,

127.4, 126.9, 126.9, 126.8, 126.7, 123.1, 123.0, 113.8, 113.7,

100.2, 98.2, 95.8, 80.44, 78.70, 77.74, 76.05, 75.47, 75.33, 74.61,

74.48, 74.04, 73.47, 72.97, 72.73, 71.67, 71.58, 69.03, 67.46,

66.59, 63.49, 55.70, 55.23, 55.15, 51.29, 33.63, 29.66, 28.80,

27.00, 25.21, 24.38, 19.27, 16.66; HRMS (M + Cs) calcd for

C

₁₀₀H₁₀₉O₂₁NSiCs 1820.6316, found 1820.6439.

C

₁₂₆H₁₃₅O₂₅NSiCs 2222.8147, found 2222.8294.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-p-m eth oxyben zyl-6-O-[2-O-ben zoyl-3-O-p-m eth -

oxyb en zyl-4-O-(2,3,4-t r i-O-b en zyl-r-^L-fu cop yr a n osyl)-6-

O-t er t -b u t yld ip h e n ylsilyl-â-^D-ga la ct op yr a n osyl]-â-D -

glu copyr an oside (48), 5-Meth oxycar bon ylpen tyl 2-Deoxy-

2-p h t h a lim id o-3-O-b en zyl-4-O-p -m et h oxyb en zyl-6-O-[2-

O-ben zoyl-3-O-p-m eth oxyben zyl-4-O-(2,3,4-tr i-O-ben zyl-

r-^L-fu c o p y r a n o s y l)-6-O -t er t -b u t y ld ip h e n y ls ily l-r-D -

galactopyranosyl]-â-^D-glucopyranoside (49),and 5-Methoxy-

ca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-ben zyl-4-O-

p -m e t h o x y b e n zy l-6-O -[2-O -b e n zo y l-3-O -p -m e t h o x y -

ben zyl-4-O-(2,3,4-tr i-O-ben zyl-â-^L-fu copyr an osyl)-6-O-ter t--

bu tyldiph en ylsilyl-â-^D-galactopyr an osyl]-â-D-glu copyr an o-

sid e (50). These three trisaccharides were prepared from 1c

(72.2 mg, 0.1337 mmol), 2c (50.0 mg, 0.06684 mmol), and 6c

(129.7 mg, 0.2005 mmol) as described in the preparation of

12, yielding 48 (73.3 mg, 65%) as a syrup, 49 (10.3 mg, 9%) as

a syrup, and 50 (11.3 mg, 10%) as a syrup. For compound 48:

¹H NMR (500 MHz, CDCl₃) δ 7.97 (dd, J ) 8.5, 1.0 Hz, 2H),

7.15-7.78 (m, 27H), 7.06 (d, J ) 9.0 Hz, 2H), 7.02 (d, J ) 7.0

Hz, 2H), 6.99 (d, J ) 8.5 Hz, 2H), 6.93 (d, J ) 7.5 Hz, 2H),

6.87-6.91 (m, 2H), 6.85 (d, J ) 7.5 Hz, 2H), 6.82 (d, J ) 8.5

Hz, 2H), 6.75 (d, J ) 8.5 Hz, 2H), 6.64 (d, J ) 9.0 Hz, 2H),

5.81 (dd, J ) 10.0, 8.0 Hz, 1H), 5.58 (d, J ) 3.5 Hz, 1H), 5.06-

5.11 (m, 1H), 4.99-5.03 (m, 1H), 4.96 (d, J ) 8.5 Hz, 1H), 4.94

(d, J ) 12.0 Hz, 1H), 4.88 (d, J ) 11.5 Hz, 1H), 4.85 (d, J )

12.0 Hz, 1H), 4.84 (d, J ) 12.5 Hz, 1H), 4.80 (dd, J ) 10.0, 4.0

Hz, 1H), 4.64-4.76 (m, 3H), 4.57 (d, J ) 11.5 Hz, 1H), 4.51 (d,

J ) 12.0 Hz, 1H), 4.48 (d, J ) 7.5 Hz, 1H), 4.43-4.47 (m, 1H),

4.39 (d, J ) 11.0 Hz, 1H), 4.29-4.34 (m, 1H), 4.23 (dd, J )

11.0, 8.5 Hz, 1H), 4.19 (d, J ) 1.5 Hz, 1H), 4.05-4.08 (m, 1H),

3.95 (dd, J ) 10.5, 7.5 Hz, 1H), 3.91 (dd, J ) 10.0, 3.5 Hz,

1H), 3.77-3.88 (m, 4H), 3.74 (s, 3H), 3.71 (s, 3H), 3.54-3.66

(m, 4H), 3.45-3.51 (m, 2H), 3.33 (d, J ) 1.0 Hz, 1H), 3.03-

3.09 (m, 1H), 1.80-1.97 (m, 2H), 1.24-1.35 (m, 4H), 1.06 (s,

9H), 0.97-1.03 (m, 2H), 0.78 (d, J ) 6.5 Hz, 3H); HRMS (M +

Cs) calcd for C₁₀₀H₁₀₉O₂₁NSiCs 1820.6316, found 1820.6419.

For compound 49: ¹H NMR (500 MHz, CDCl₃) δ 7.93 (d, J )

8.0 Hz, 2H), 7.62 (d, J ) 8.0 Hz, 4H), 7.58 (d, J ) 8.0 Hz, 2H),

7.48 (t, J ) 7.5 Hz, 1H), 7.24-7.43 (m, 23H), 7.19 (t, J ) 7.5

Hz, 2H), 7.14 (d, J ) 8.5 Hz, 2H), 7.04 (d, J ) 8.5 Hz, 2H),

6.92 (d, J ) 8.5 Hz, 2H), 6.81-6.87 (m, 3H), 6.69 (d, J ) 8.5

Hz, 2H), 6.64 (d, J ) 9.0 Hz, 2H), 5.52 (dd, J ) 10.0, 8.0 Hz,

ben zyl-4-O-[2-O-ben zoyl-3-O-(2,3,4,6-tetr a -O-ben zyl-r-^D-

m a n n op yr a n osyl)-4-O-levu lin yl-6-O-ter t-bu tyld ip h en yl-

silyl-â-^D-ga la ct op yr a n osyl]-6-O-p -m e t h oxyb e n zyl-â-D-

glu cop yr a n osid e (45) a n d 5-Meth oxyca r bon ylp en tyl

2-Deoxy-2-p h t h a lim id o-3-O-b en zyl-4-O-[2-O-b en zoyl-3-

O -(2,3,4,6-t e t r a -O -b e n zy l-â-^D-m a n n o p y r a n o s y l)-4-O -

levu lin yl-6-O-ter t-bu tyld ip h en ylsilyl-â-^D-ga la ctop yr a n o-

syl]-6-O-p-m eth oxyben zyl-â-^D-glu copyr an oside (46). These

two trisaccharides were prepared from 1e (33.4 mg, 0.05165

mmol), 2b (25.0 mg, 0.03444 mmol), and 6b (66.8 mg, 0.1033

mmol) as described in the preparation of 29, yielding 45 (30.4

mg, 50%) as a syrup and 46 (9.7 mg, 16%) as a syrup. For

compound 45: ¹H NMR (400 MHz, CDCl₃) δ 8.00 (d, J ) 8.1

Hz, 2H), 6.75-7.74 (m, 46H), 5.68 (d, J ) 2.9 Hz, 1H), 5.33

(dd, J ) 10.0, 8.2 Hz, 1H), 5.29 (s, 1H), 4.94 (d, J ) 8.4 Hz,

1H), 4.67-4.76 (m, 4H), 4.64 (d, J ) 11.5 Hz, 1H), 4.58 (d, J

) 12.1 Hz, 1H), 4.54 (d, J ) 11.7 Hz, 1H), 4.51 (d, J ) 11.6

Hz, 1H), 4.47 (d, J ) 11.8 Hz, 2H), 4.38 (d, J ) 12.1 Hz, 1H),

4.28 (d, J ) 11.6 Hz, 1H), 4.24 (d, J ) 11.6 Hz, 1H), 4.19 (dd,

J ) 10.6, 8.5 Hz, 1H), 4.07 (d, J ) 8.8 Hz, 1H), 4.05 (dd, J )

10.0, 6.5 Hz, 1H), 3.98 (t, J ) 9.1 Hz, 1H), 3.76-3.81 (m, 1H),

3.75 (s, 3H), 3.63-3.73 (m, 5H), 3.57 (s, 3H), 3.51-3.56 (m,

4H), 3.46 (t, J ) 9.1 Hz, 1H), 3.39 (dd, J ) 10.3, 5.1 Hz, 1H),

3.33 (d, J ) 9.6 Hz, 1H), 3.25 (dt, J ) 9.5, 6.5 Hz, 1H), 2.45-

2.59 (m, 3H), 2.32-2.40 (m, 1H), 2.01 (s, 3H), 1.88-1.97 (m,

2H), 1.26-1.37 (m, 4H), 1.04 (s, 9H), 0.83-0.92 (m, 2H); ¹³C

NMR (100 MHz, CDCl₃) δ 205.53, 173.85, 171.46, 164.80,

159.25, 138.99, 138.96, 138.70, 138.46, 138.23, 135.61, 135.49,

133.65, 133.14, 132.86, 132.84, 130.23, 129.79, 129.41, 129.20,

128.28, 128.10, 128.00, 127.77, 127.73, 127.66, 127.49, 127.16,

127.10, 126.92, 126.80, 113.78, 100.50, 98.12, 94.14, 79.31,

77.76, 77.06, 74.70, 74.66, 74.41, 74.06, 74.00, 73.42, 72.87,

72.73, 72.52, 71.96, 71.96, 71.74, 71.14, 69.27, 69.07, 67.45,

64.94, 60.51, 55.60, 55.22, 51.33, 37.76, 33.66, 29.67, 28.79,

27.79, 26.77, 25.24, 24.32, 19.05; HRMS (M + Cs) calcd for

C

₁₀₄H₁₁₃O₂₃NSiCs 1904.6527, found 1904.6638. For compound

46: ¹H NMR (400 MHz, CDCl₃) δ 6.64-7.97 (m, 48H), 3.20-

5.72 (m, 41H), 2.28-2.49 (m, 4H), 1.88-1.96 (m, 2H), 1.80 (s,

3H), 1.25-1.36 (m, 4H), 1.09 (s, 9H), 0.83-0.89 (m, 2H); HRMS

(M + Cs) calcd for

1904.6638.

C₁₀₄H₁₁₃O₂₃NSiCs 1904.6527, found

2426 J . Org. Chem., Vol. 65, No. 8, 2000

Ye and Wong

1H), 5.15 (d, J ) 11.0 Hz, 1H), 4.99 (d, J ) 11.5 Hz, 1H), 4.89

(s, 1H), 4.87 (d, J ) 3.0 Hz, 1H), 4.78 (d, J ) 10.5 Hz, 1H),

4.77 (d, J ) 3.0 Hz, 1H), 4.75 (d, J ) 8.5 Hz, 1H), 4.72 (d, J )

12.0 Hz, 1H), 4.66 (d, J ) 12.0 Hz, 1H), 4.65 (d, J ) 12.0 Hz,

1H), 4.57 (d, J ) 7.0 Hz, 1H), 4.56 (d, J ) 11.0 Hz, 1H), 4.48

(d, J ) 11.0 Hz, 2H), 4.40 (d, J ) 10.5 Hz, 1H), 4.31 (d, J )

12.5 Hz, 1H), 4.26 (t, J ) 9.5 Hz, 1H), 4.14-4.20 (m, 2H), 4.07

(t, J ) 6.5 Hz, 1H), 3.94-4.01 (m, 2H), 3.74-3.80 (m, 1H),

3.73 (s, 3H), 3.68 (s, 3H), 3.58 (s, 3H), 3.54-3.57 (m, 3H), 3.49

(d, J ) 3.0 Hz, 1H), 3.29-3.43 (m, 4H), 2.92-2.96 (m, 1H),

1.77-1.87 (m, 2H), 1.18-1.25 (m, 4H), 1.15 (d, J ) 6.5 Hz,

3H), 1.03 (s, 9H), 0.97-1.00 (m, 2H); HRMS (M + Cs) calcd

for C₁₀₀H₁₀₉O₂₁NSiCs 1820.6316, found 1820.6418. For com-

pound 50: ¹H NMR (400 MHz, CDCl₃) δ 7.96 (dd, J ) 8.5, 1.4

Hz, 2H), 7.16-7.76 (m, 32H), 7.06 (d, J ) 8.7 Hz, 2H), 6.99 (d,

J ) 8.6 Hz, 2H), 6.79-6.94 (m, 5H), 6.75 (d, J ) 8.7 Hz, 2H),

6.64 (d, J ) 8.7 Hz, 2H), 5.80 (dd, J ) 10.1, 8.0 Hz, 1H), 5.58

(d, J ) 3.8 Hz, 1H), 5.00 (d, J ) 11.6 Hz, 1H), 4.96 (d, J ) 8.4

Hz, 1H), 4.94 (d, J ) 11.8 Hz, 1H), 4.87 (dd, J ) 11.5, 4.7 Hz,

1H), 4.83 (d, J ) 12.1 Hz, 1H), 4.76 (d, J ) 11.8 Hz, 1H), 4.64-

4.70 (m, 4H), 4.57 (dd, J ) 9.7, 3.1 Hz, 1H), 4.56 (d, J ) 11.6

Hz, 1H), 4.51 (d, J ) 11.7 Hz, 1H), 4.48 (d, J ) 11.5 Hz, 1H),

4.37-4.46 (m, 3H), 4.32 (d, J ) 12.2 Hz, 1H), 4.27-4.31 (m,

1H), 4.22 (dd, J ) 10.8, 8.5 Hz, 1H), 4.19 (d, J ) 1.6 Hz, 1H),

4.04-4.09 (m, 2H), 3.89-3.95 (m, 1H), 3.58-3.80 (m, 12H),

3.44-3.50 (m, 2H), 3.33 (d, J ) 2.2 Hz, 1H), 3.04-3.08 (m,

1H), 1.77-1.89 (m, 2H), 1.17-1.35 (m, 4H), 1.06 (s, 9H), 0.98-

1.04 (m, 2H), 0.77 (d, J ) 6.4 Hz, 3H); HRMS (M + Cs) calcd

for C₁₀₀H₁₀₉O₂₁NSiCs 1820.6316, found 1820.6418.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

[2-O-b e n zoyl-3-O-p -m e t h oxyb e n zyl-4-O-le vu lin yl-6-O-

(2,3,4,6-tetr a -O-ben zyl-r-^D-ga la ctop yr a n osyl)-â-D-ga la c-

t o p y r a n o s y l ] -4 ,6 -O -p -m e t h o x y b e n z y l i d e n e -â-^D-

glu cop yr a n osid e (51). This trisaccharide was prepared from

1a (79.7 mg, 0.1234 mmol), 2d (50.0 mg, 0.08224 mmol), and

6a (136.9 mg, 0.2467 mmol) as described in the preparation

of 12, yielding product (95.0 mg, 74%) as a syrup: ¹H NMR

(500 MHz, CDCl₃) δ 7.21-7.42 (m, 31H), 6.83 (d, J ) 8.5 Hz,

2H), 6.71 (d, J ) 8.5 Hz, 2H), 6.39 (d, J ) 8.5 Hz, 2H), 5.50 (d,

J ) 3.5 Hz, 1H), 5.43 (s, 1H), 5.10 (dd, J ) 10.0, 8.0 Hz, 1H),

5.06 (d, J ) 8.5 Hz, 1H), 4.91 (d, J ) 11.5 Hz, 1H), 4.82 (d, J

) 11.5 Hz, 1H), 4.65-4.72 (m, 6H), 4.60 (d, J ) 11.5 Hz, 1H),

4.54 (d, J ) 11.5 Hz, 1H), 4.49 (d, J ) 11.5 Hz, 1H), 4.39 (d,

J ) 11.5 Hz, 1H), 4.33 (d, J ) 12.0 Hz, 1H), 4.23-4.28 (m,

2H), 4.06 (t, J ) 6.5 Hz, 1H), 3.99 (d, J ) 12.0 Hz, 1H), 3.95

(dd, J ) 10.0, 3.5 Hz, 1H), 3.84 (d, J ) 2.5 Hz, 1H), 3.63-3.75

(m, 3H), 3.64 (s, 3H), 3.63 (s, 3H), 3.57 (s, 3H), 3.48-3.55 (m,

3H), 3.43 (dd, J ) 9.0, 5.0 Hz, 1H), 3.38 (dd, J ) 10.0, 3.0 Hz,

1H), 3.37 (s, 1H), 3.33 (dd, J ) 10.5, 3.5 Hz, 1H), 3.26-3.31

(m, 1H), 2.57-2.70 (m, 4H), 2.08 (s, 3H), 1.81-1.94 (m, 2H),

1.21-1.38 (m, 4H), 0.95-1.03 (m, 2H); HRMS (M + Cs) calcd

for C₈₉H₉₅O₂₄NCs 1694.5298, found 1694.5398.

5-Met h oxyca r b on ylp en t yl 2-Deoxy-2-p h t h a lim id o-3-

O-b e n zyl-4-O-[2-O-b e n zoyl-3-O-p -m e t h oxyb e n zyl-4-O-

levu lin yl-6-O-(2,3,4,6-tetr a -O-ben zyl-r-^D-ga la ctop yr a n o-

syl)-â-^D-ga la ctop yr a n osyl]-6-O-p-m eth oxyben zyl-â-D-glu -

copyr an oside (52) an d 5-Meth oxycar bon ylpen tyl 2-Deoxy-

2-p h t h a li m i d o -3-O -b e n z y l-4-O -[2-O -b e n z o y l-3-O -p -

m eth oxyben zyl-4-O-levu lin yl-6-O-(2,3,4,6-tetr a -O-ben zyl-

â-^D-g a la c t o p y r a n o s y l)-â-D -g a la c t o p y r a n o s y l]-6-O -p -

m eth oxyben zyl-â-^D-glu cop yr a n osid e (53). These two tri-

saccharides were prepared from 1a (79.7 mg, 0.1234 mmol),

2d (46.3 mg, 0.07615 mmol), and 6b (159.6 mg, 0.2467 mmol)

as described in the preparation of 12, yielding 52 (80.3 mg,

64%) as a syrup and 53 (18.9 mg, 15%) as a syrup. For

compound 52: ¹H NMR (500 MHz, CDCl₃) δ 7.94 (d, J ) 8.0

Hz, 2H), 7.66-7.78 (m, 3H), 7.61 (t, J ) 7.5 Hz, 2H), 7.47 (t,

J ) 8.0 Hz, 2H), 7.43 (d, J ) 7.0 Hz, 2H), 7.40 (d, J ) 7.5 Hz,

2H), 7.34 (d, J ) 7.0 Hz, 2H), 7.22-7.32 (m, 14H), 7.20 (d, J

) 8.5 Hz, 2H), 7.03 (d, J ) 6.5 Hz, 2H), 6.93 (d, J ) 8.5 Hz,

2H), 6.81-6.87 (m, 5H), 6.58 (d, J ) 8.5 Hz, 2H), 5.57 (d, J )

3.5 Hz, 1H), 5.32 (dd, J ) 9.5, 8.0 Hz, 1H), 4.97 (d, J ) 8.5 Hz,

1H), 4.95 (d, J ) 10.0 Hz, 1H), 4.93 (d, J ) 3.5 Hz, 1H), 4.86

(d, J ) 12.5 Hz, 1H), 4.82 (d, J ) 12.0 Hz, 1H), 4.79 (d, J )

10.0 Hz, 1H), 4.77 (d, J ) 12.0 Hz, 1H), 4.70 (d, J ) 11.5 Hz,

1H), 4.64 (d, J ) 8.0 Hz, 1H), 4.60 (d, J ) 11.5 Hz, 1H), 4.55

(d, J ) 12.0 Hz, 1H), 4.52 (d, J ) 12.5 Hz, 1H), 4.50 (d, J )

13.0 Hz, 1H), 4.48 (d, J ) 11.5 Hz, 1H), 4.36 (d, J ) 12.0 Hz,

1H), 4.27 (d, J ) 12.0 Hz, 1H), 4.20 (dd, J ) 10.5, 8.5 Hz, 1H),

4.17 (d, J ) 12.0 Hz, 1H), 4.04-4.12 (m, 4H), 4.01 (q, J ) 6.5

Hz, 1H), 3.94 (dd, J ) 10.0, 2.5 Hz, 1H), 3.71 (s, 3H), 3.70 (s,

3H), 3.54-3.68 (m, 6H), 3.57 (s, 3H), 3.46-3.51 (m, 3H), 3.34

(d, J ) 10.0 Hz, 1H), 3.26 (dt, J ) 9.5, 6.5 Hz, 1H), 2.54-2.67

(m, 4H), 2.02 (s, 3H), 1.86-1.97 (m, 2H), 1.26-1.42 (m, 4H),

0.97-1.04 (m, 2H); ¹³C NMR (125 MHz, CDCl₃) δ 206.0, 173.8,

171.9, 164.9, 159.2, 159.0, 138.9, 138.8, 138.7, 138.5, 138.0,

133.6, 133.1, 130.3, 129.8, 129.8, 129.6, 129.4, 129.3, 128.3,

128.2, 128.2, 128.2, 128.1, 128.1, 128.0, 127.9, 127.8, 127.6,

127.4, 127.4, 127.3, 127.0, 123.1, 113.8, 113.5, 100.5, 98.3, 98.1,

78.96, 77.83, 76.68, 76.55, 76.38, 74.94, 74.76, 74.62, 74.43,

73.56, 72.95, 72.93, 72.83, 71.89, 71.76, 70.62, 69.66, 69.14,

69.03, 67.34, 66.25, 65.85, 55.77, 55.20, 55.08, 51.29, 38.03,

33.61, 29.53, 28.79, 28.04, 25.19, 24.32; HRMS (M + Cs) calcd

for C₉₆H₁₀₃O₂₄NCs 1786.5924, found 1786.6022. For compound

53: ¹H NMR (500 MHz, CDCl₃) δ 7.96 (d, J ) 8.0 Hz, 2H),

7.17-7.59 (m, 27H), 7.09 (d, J ) 9.0 Hz, 2H), 7.02 (t, J ) 7.5

Hz, 2H), 6.99 (d, J ) 8.5 Hz, 2H), 6.77-6.82 (m, 5H), 6.64 (d,

J ) 8.5 Hz, 2H), 5.46 (d, J ) 3.5 Hz, 1H), 5.27 (dd, J ) 9.5,

8.0 Hz, 1H), 5.00 (d, J ) 8.0 Hz, 1H), 4.97 (d, J ) 10.5 Hz,

1H), 4.90 (d, J ) 12.0 Hz, 1H), 4.87 (d, J ) 13.0 Hz, 1H), 4.85

(d, J ) 10.0 Hz, 2H), 4.84 (d, J ) 8.0 Hz, 1H), 4.65 (d, J )

11.5 Hz, 1H), 4.49 (d, J ) 12.0 Hz, 1H), 4.48 (d, J ) 12.0 Hz,

1H), 4.44 (d, J ) 12.0 Hz, 1H), 4.39 (d, J ) 8.0 Hz, 1H), 4.37

(d, J ) 11.5 Hz, 1H), 4.28 (d, J ) 11.5 Hz, 1H), 4.21 (d, J )

11.5 Hz, 1H), 3.95-4.18 (m, 7H), 3.86 (dd, J ) 10.0, 2.5 Hz,

1H), 3.74-3.83 (m, 3H), 3.73 (s, 6H), 3.58-3.71 (m, 5H), 3.56

(s, 3H), 3.39-3.44 (m, 3H), 3.23-3.29 (m, 1H), 2.54-2.69 (m,

4H), 2.01 (s, 3H), 1.87-1.94 (m, 2H), 1.26-1.40 (m, 4H), 0.97-

1.02 (m, 2H); HRMS (M + Cs) calcd for C₉₆H₁₀₃O₂₄NCs

1786.5924, found 1786.6030.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-p-m eth oxyben zyl-6-O-[2-O-ben zoyl-3-O-p-m eth -

oxyben zyl-4-O-levu lin yl-6-O-(2,3,4,6-tetr a -O-ben zyl-r-^D-

ga la ctop yr a n osyl)-â-^D-ga la ctop yr a n osyl]-â-D-glu cop yr a -

n osid e (54) a n d 5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-

p h th a lim id o-3-O-ben zyl-4-O-p-m eth oxyben zyl-6-O-[2-O-

b e n z o y l -3 -O -p -m e t h o x y b e n z y l -4 -O -l e v u l i n y l -6 -O -

(2,3,4,6-t et r a -O-b en zyl-â-^D-ga la ct op yr a n osyl)-â-D-ga la c-

top yr a n osyl]-â-^D-glu cop yr a n osid e (55). These two trisac-

charides were prepared from 1a (79.7 mg, 0.1234 mmol), 2d

(46.3 mg, 0.07615 mmol), and 6c (159.6 mg, 0.2467 mmol) as

described in the preparation of 12, yielding 54 (86.0 mg, 68%)

and 55 (22.1 mg, 18%) as syrups. For compound 54: ¹H NMR

(500 MHz, CDCl₃) δ 7.90 (d, J ) 7.0 Hz, 2H), 7.59-7.75 (m,

4H), 7.50 (t, J ) 7.5 Hz, 1H), 7.44 (d, J ) 7.0 Hz, 2H), 7.39 (d,

J ) 7.0 Hz, 2H), 7.22-7.36 (m, 18H), 7.06 (d, J ) 8.5 Hz, 2H),

6.95 (d, J ) 8.5 Hz, 2H), 6.93 (d, J ) 8.0 Hz, 2H), 6.82-6.88

(m, 3H), 6.79 (d, J ) 8.5 Hz, 2H), 6.56 (d, J ) 8.5 Hz, 2H),

5.60 (d, J ) 3.0 Hz, 1H), 5.40 (dd, J ) 10.0, 8.0 Hz, 1H), 5.00

(d, J ) 3.5 Hz, 1H), 4.94 (d, J ) 8.5 Hz, 1H), 4.93 (d, J ) 11.5

Hz, 1H), 4.84 (d, J ) 11.5 Hz, 1H), 4.76 (d, J ) 12.0 Hz, 1H),

4.72 (d, J ) 11.5 Hz, 1H), 4.71 (d, J ) 11.5 Hz, 1H), 4.66 (d,

J ) 12.0 Hz, 1H), 4.58 (d, J ) 8.0 Hz, 1H), 4.54 (d, J ) 11.5

Hz, 1H), 4.50 (d, J ) 12.0 Hz, 1H), 4.48 (d, J ) 11.5 Hz, 1H),

4.45 (d, J ) 10.5 Hz, 1H), 4.41 (d, J ) 10.5 Hz, 1H), 4.40 (d,

J ) 12.0 Hz, 1H), 4.31 (d, J ) 12.0 Hz, 1H), 4.21 (d, J ) 12.0

Hz, 1H), 4.20 (d, J ) 11.0 Hz, 1H), 4.18 (d, J ) 11.0 Hz, 1H),

4.01-4.08 (m, 3H), 3.97 (d, J ) 1.5 Hz, 1H), 3.93 (dd, J ) 10.0,

3.0 Hz, 1H), 3.85 (t, J ) 6.0 Hz, 1H), 3.74-3.81 (m, 2H), 3.73

(s, 3H), 3.69 (s, 3H), 3.54-3.65 (m, 8H), 3.40-3.45 (m, 2H),

3.02-3.06 (m, 1H), 2.64-2.78 (m, 4H), 2.13 (s, 3H), 1.79-1.90

(m, 2H), 1.19-1.32 (m, 4H), 1.04-1.17 (m, 2H); ¹³C NMR (125

MHz, CDCl₃) δ 206.3, 173.8, 172.0, 165.0, 159.2, 159.0, 138.8,

138.6, 138.0, 133.6, 132.8, 129.9, 129.9, 129.7, 129.4, 129.3,

128.4, 128.3, 128.2, 128.2, 128.1, 128.0, 127.9, 127.7, 127.7,

127.5, 127.5, 127.4, 127.3, 127.2, 113.7, 113.5, 101.2, 98.4, 97.8,

79.42, 79.09, 78.82, 76.52, 76.11, 75.09, 74.70, 74.59, 74.49,

74.37, 73.40, 73.04, 72.96, 72.05, 71.06, 70.46, 69.73, 69.24,

68.72, 67.90, 66.78, 66.55, 55.71, 55.17, 55.04, 51.28, 38.12,

33.58, 29.68, 28.61, 28.23, 25.21, 24.27; HRMS (M + Cs) calcd

One-Pot Oligosaccharide Synthesis

J . Org. Chem., Vol. 65, No. 8, 2000 2427

for C₉₆H₁₀₃O₂₄NCs 1786.5924, found 1786.6008. For compound

55: ¹H NMR (500 MHz, CDCl₃) δ 7.88 (d, J ) 7.5 Hz, 2H),

7.59-7.76 (m, 4H), 7.48 (t, J ) 7.5 Hz, 1H), 7.39 (d, J ) 7.0

Hz, 2H), 7.22-7.36 (m, 20H), 6.98 (d, J ) 8.5 Hz, 2H), 6.95 (d,

J ) 8.5 Hz, 2H), 6.92 (d, J ) 7.0 Hz, 2H), 6.81-6.88 (m, 3H),

6.77 (d, J ) 8.5 Hz, 2H), 6.58 (d, J ) 8.5 Hz, 2H), 5.51 (d, J )

3.0 Hz, 1H), 5.38 (dd, J ) 9.5, 8.5 Hz, 1H), 4.96 (d, J ) 11.5

Hz, 1H), 4.92 (d, J ) 11.5 Hz, 1H), 4.88 (d, J ) 8.0 Hz, 1H),

4.78 (d, J ) 11.0 Hz, 1H), 4.65 (d, J ) 11.5 Hz, 2H), 4.60 (d,

J ) 12.5 Hz, 2H), 4.47 (d, J ) 12.5 Hz, 1H), 4.46 (d, J ) 7.5

Hz, 1H), 4.44 (d, J ) 11.5 Hz, 1H), 4.29 (d, J ) 10.5 Hz, 1H),

4.25 (d, J ) 11.0 Hz, 1H), 4.21 (d, J ) 12.0 Hz, 1H), 4.14 (d,

J ) 10.5 Hz, 1H), 4.13 (d, J ) 8.5 Hz, 1H), 4.06 (t, J ) 6.5 Hz,

1H), 4.01 (d, J ) 11.0 Hz, 1H), 3.99 (d, J ) 11.0 Hz, 1H), 3.92-

3.96 (m, 1H), 3.90 (d, J ) 2.5 Hz, 1H), 3.75-3.85 (m, 3H), 3.74

(s, 3H), 3.70 (s, 3H), 3.55-3.62 (m, 9H), 3.41-3.47 (m, 3H),

3.30 (t, J ) 8.5 Hz, 1H), 2.98-3.03 (m, 1H), 2.66-2.75 (m, 4H),

2.15 (s, 3H), 1.79-1.91 (m, 2H), 1.22-1.31 (m, 4H), 1.04-1.17

(m, 2H); HRMS (M + Cs) calcd for C₉₆H₁₀₃O₂₄NCs 1786.5924,

found 1786.6012.

HRMS (M + Cs) calcd for C₉₈H₁₁₁O₂₂NSiCs 1814.6421, found

1814.6525. For compound 58: ¹H NMR (500 MHz, CDCl₃) δ

7.17-7.77 (m, 30H), 7.08 (d, J ) 8.5 Hz, 2H), 6.97 (d, J ) 7.0

Hz, 2H), 6.83-6.90 (m, 4H), 6.75 (d, J ) 8.5 Hz, 2H), 6.72 (d,

J ) 8.5 Hz, 2H), 5.62 (d, J ) 3.0 Hz, 1H), 5.00 (d, J ) 8.5 Hz,

1H), 4.98 (d, J ) 12.5 Hz, 1H), 4.93 (d, J ) 7.5 Hz, 1H), 4.92

(d, J ) 11.0 Hz, 1H), 4.65-4.78 (m, 6H), 4.62 (d, J ) 11.0 Hz,

2H), 4.54 (d, J ) 11.0 Hz, 1H), 4.46 (d, J ) 10.5 Hz, 1H), 4.40

(d, J ) 8.0 Hz, 1H), 4.38 (d, J ) 12.5 Hz, 1H), 4.26 (dd, J )

11.0, 8.5 Hz, 1H), 3.98-4.10 (m, 4H), 3.71 (s, 3H), 3.69 (s, 3H),

3.59-3.81 (m, 6H), 3.57 (s, 3H), 3.44-3.53 (m, 3H), 3.28 (q, J

) 6.0 Hz, 1H), 3.21 (dt, J ) 9.5, 6.5 Hz, 1H), 2.51-2.57 (m,

4H), 2.04 (s, 3H), 1.80-1.88 (m, 2H), 1.17-1.25 (m, 4H), 1.12

(d, J ) 6.5 Hz, 3H), 1.05 (s, 9H), 0.93-1.01 (m, 2H); HRMS

(M + Cs) calcd for C₉₈H₁₁₁O₂₂NSiCs 1814.6421, found 1814.6314.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-

O-ben zyl-4-O-[2-O-ben zoyl-3-O-(2-d eoxy-2-a zid o-3,4,6-tr i-

O-b en zyl-r-^D-ga la ct op yr a n osyl)-4-O-levu lin yl-6-O-ter t-

bu tyld ip h en ylsilyl-â-^D-ga la ctop yr a n osyl]-6-O-p-m eth oxy-

ben zyl-â-^D-glu cop yr a n osid e (59). This trisaccharide was

prepared from 1d (24.0 mg, 0.04132 mmol), 2b (20.0 mg,

0.02755 mmol), and 6b (53.5 mg, 0.08264 mmol) as described

in the preparation of 29, yielding product (22.1 mg, 47%) as a

syrup: ¹H NMR (400 MHz, CDCl₃) δ 8.06 (dd, J ) 8.1, 1.2 Hz,

2H), 7.56-7.74 (m, 8H), 7.51 (t, J ) 7.4 Hz, 1H), 7.22-7.42

(m, 21H), 7.20 (d, J ) 8.6 Hz, 2H), 7.10-7.13 (m, 2H), 6.91-

6.94 (m, 2H), 6.85 (d, J ) 8.6 Hz, 2H), 6.75-6.79 (m, 3H), 5.72

(d, J ) 3.1 Hz, 1H), 5.46 (dd, J ) 10.1, 8.0 Hz, 1H), 5.23 (d, J

) 3.4 Hz, 1H), 4.95 (d, J ) 8.5 Hz, 1H), 4.75 (d, J ) 7.9 Hz,

1H), 4.74 (d, J ) 13.0 Hz, 1H), 4.70 (d, J ) 11.4 Hz, 1H), 4.50

(d, J ) 11.7 Hz, 2H), 4.48 (d, J ) 11.2 Hz, 1H), 4.38 (d, J )

12.0 Hz, 1H), 4.35 (d, J ) 11.0 Hz, 1H), 4.33 (d, J ) 11.8 Hz,

1H), 4.29 (d, J ) 11.6 Hz, 1H), 4.25 (d, J ) 11.6 Hz, 1H), 4.21

(dd, J ) 10.7, 8.5 Hz, 1H), 4.06 (dd, J ) 10.7, 8.5 Hz, 1H),

3.95-4.02 (m, 2H), 3.84 (t, J ) 6.5 Hz, 1H), 3.77 (dd, J ) 10.6,

3.3 Hz, 1H), 3.75 (s, 3H), 3.63-3.71 (m, 3H), 3.57 (s, 3H), 3.49-

3.55 (m, 4H), 3.47 (dt, J ) 9.5, 6.5 Hz, 1H), 3.22-3.38 (m, 4H),

2.70-2.81 (m, 1H), 2.57-2.69 (m, 3H), 2.09 (s, 3H), 1.86-1.97

(m, 2H), 1.28-1.37 (m, 4H), 1.02 (s, 9H), 0.83-0.90 (m, 2H);

¹³C NMR (100 MHz, CDCl₃) δ 206.05, 173.87, 171.57, 164.54,

159.23, 138.41, 138.04, 137.91, 137.50, 135.65, 135.50, 133.68,

133.39, 133.03, 132.76, 130.23, 129.81, 129.74, 129.42, 129.28,

128.61, 128.44, 128.20, 128.06, 127.87, 127.83, 127.73, 127.65,

126.94, 113.72, 100.50, 98.14, 94.08, 78.02, 77.55, 77.19, 74.70,

74.57, 74.53, 73.48, 73.17, 73.14, 72.88, 72.59, 72.50, 71.57,

69.92, 69.07, 68.95, 67.47, 64.58, 60.65, 59.38, 55.63, 55.22,

51.35, 37.95, 33.67, 29.68, 28.81, 27.84, 26.74, 25.25, 24.34,

19.03; HRMS (M + Cs) calcd for C₉₇H₁₀₆O₂₂N₄SiCs 1839.6122,

found 1839.6251.

5-Met h oxyca r b on ylp en t yl 2-Deoxy-2-p h t h a lim id o-3-

O -(2-O -b e n zo y l-3-O -r-^D-g lu c o p y r a n o s y l-â-D -g a la c t o -

p yr a n osyl)-â-^D-glu cop yr a n osid e (61). A mixture of 5-meth-

oxycarbonylpentyl 2-deoxy-2-phthalimido-3-O-[2-O-benzoyl-3-

O-(2,3,4,6-tetra-O-benzyl-R-^D-glucopyranosyl)-4-O-levulinyl-6-

O-ter t-bu t yldiph en ylsilyl-â-^D-ga la ct opyr a n osyl]-4,6-O-p-

methoxybenzylidne-â-^D-glucopyranoside (73.1 mg, 0.0435 mmol),

HF-pyridine complex (0.6 mL), acetic acid (1.2 mL), and dry

THF (6 mL) was stirred overnight under argon. The reaction

mixture was diluted with EtOAc, washed with saturated

NaHCO₃and brine, and dried over Na₂SO₄. The dried organic

layer was concentrated under reduced pressure, and the

residue was purified by chromatography on a silica gel column

(EtOAc) to yield a syrup.

To a stirred solution of above syrup in THF-MeOH (10:1

v/v, 5.5 mL), 1 M hydrazine-acetic acid (1:2.5 v/v) in THF-

MeOH (5:1 v/v) (1 mL) was added. The reaction mixture was

stirred overnight. The solvent was then removed, and the

residue was diluted with EtOAc. The organic layer was washed

with saturated NaHCO₃and brine and dried over Na₂SO₄. The

dried organic layer was concentrated under reduced pressure,

and the residue was purified by chromatography on a silica

gel column (EtOAc) to give 60 (47.0 mg, 88%) as a thick oil.

A mixture of 60 (18.0 mg, 0.01469 mmol), 10% Pd-C (7.0

mg) in HOAc (2.0 mL), THF (1.0 mL), and H₂O (0.5 mL) was

stirred overnight under H₂atmosphere. The catalyst was then

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-p-m eth oxyben zyl-6-O-[2-O-(2,3,4-O-ben zyl-r-

L-fu cop yr a n osyl)-3-O-p-m eth oxyben zyl-4-O-levu lin yl-6-

O-t er t -b u t yld ip h e n ylsilyl-r-^D-ga la ct op yr a n osyl]-â-D -

glu copyr an oside (56), 5-Meth oxycar bon ylpen tyl 2-Deoxy-

2-p h t h a lim id o-3-O-b en zyl-4-O-p -m et h oxyb en zyl-6-O-[2-

O -( 2 , 3 , 4 -O -b e n z y l -r-^L-f u c o p y r a n o s y l ) -3 -O -p -

m eth oxyben zyl-4-O-levu lin yl-6-O-ter t-bu tyldiph en ylsilyl-

â-^D-ga la ct op yr a n osyl]-â-D-glu cop yr a n osid e (57), a n d

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-p h th a lim id o-3-O-

ben zyl-4-O-p-m eth oxyben zyl-6-O-[2-O-(2,3,4-O-ben zyl-â-

L-fu cop yr a n osyl)-3-O-p-m eth oxyben zyl-4-O-levu lin yl-6-

O-t er t -b u t yld ip h e n ylsilyl-â-^D-ga la ct op yr a n osyl]-â-D -

glu cop yr a n osid e (58). These three trisaccharides were

prepared from 1c (54.6 mg, 0.1011 mmol), 2a (50.0 mg, 0.06738

mmol), and 6c (130.8 mg, 0.2021 mmol) as described in the

preparation of 12, yielding 56 (37.5 mg, 33%), 57 (36.1 mg,

32%), and 58 (11.1 mg, 10%) as syrups. For compound 56: ¹H

NMR (500 MHz, CDCl₃) δ 6.80-7.68 (m, 38H), 6.70 (d, J )

7.0 Hz, 2H), 6.65 (d, J ) 8.5 Hz, 2H), 5.55 (d, J ) 2.5 Hz, 1H),

5.32 (d, J ) 3.5 Hz, 1H), 5.22 (d, J ) 4.0 Hz, 1H), 5.10 (d, J )

11.5 Hz, 1H), 5.03 (d, J ) 11.5 Hz, 1H), 4.98 (d, J ) 8.5 Hz,

1H), 4.83 (d, J ) 12.5 Hz, 2H), 4.80 (d, J ) 12.0 Hz, 1H), 4.67-

4.73 (m, 4H), 4.49 (d, J ) 12.5 Hz, 1H), 4.44 (d, J ) 12.0 Hz,

1H), 4.42 (d, J ) 2.5 Hz, 1H), 4.32 (d, J ) 12.5 Hz, 1H), 4.25-

4.29 (m, 2H), 4.12 (dd, J ) 10.0, 3.5 Hz, 1H), 4.01-4.06 (m,

2H), 3.95 (dd, J ) 10.5, 3.5 Hz, 1H), 3.84-3.91 (m, 3H), 3.65-

3.79 (m, 4H), 3.64 (s, 3H), 3.62 (s, 3H), 3.56 (s, 3H), 3.47-3.54

(m, 2H), 3.25 (dt, J ) 9.5, 7.0 Hz, 1H), 2.54-2.68 (m, 4H), 2.11

(s, 3H), 1.82-1.94 (m, 2H), 1.24-1.34 (m, 4H), 1.21 (d, J )

6.5 Hz, 3H), 1.05 (s, 9H), 0.93-1.01 (m, 2H); HRMS (M + Cs)

calcd for C₉₈H₁₁₁O₂₂NSiCs 1814.6421, found 1814.6524. For

compound 57: ¹H NMR (500 MHz, CDCl₃) δ 7.16-7.77 (m,

30H), 7.10 (d, J ) 8.5 Hz, 4H), 6.93 (d, J ) 7.0 Hz, 2H), 6.82

(d, J ) 9.0 Hz, 2H), 6.78 (d, J ) 7.0 Hz, 2H), 6.77 (d, J ) 8.5

Hz, 2H), 5.69 (d, J ) 3.5 Hz, 1H), 5.60 (d, J ) 3.0 Hz, 1H),

5.07 (d, J ) 8.5 Hz, 1H), 5.05 (d, J ) 12.0 Hz, 1H), 4.89 (d, J

) 11.5 Hz, 1H), 4.83 (d, J ) 11.0 Hz, 1H), 4.80 (d, J ) 10.5

Hz, 1H), 4.78 (d, J ) 11.0 Hz, 1H), 4.72 (d, J ) 8.5 Hz, 1H),

4.71 (d, J ) 12.5 Hz, 1H), 4.65 (d, J ) 8.5 Hz, 1H), 4.64 (s,

2H), 4.53 (q, J ) 6.5 Hz, 1H), 4.38 (d, J ) 12.0 Hz, 1H), 4.35

(dd, J ) 10.0, 8.0 Hz, 1H), 4.30 (d, J ) 10.5 Hz, 1H), 4.20 (d,

J ) 8.0 Hz, 1H), 4.14 (s, 1H), 3.95-4.13 (m, 5H), 3.76 (s, 3H),

3.72-3.75 (m, 2H), 3.71 (s, 3H), 3.59-3.69 (m, 5H), 3.57 (s,

3H), 3.52 (t, J ) 7.0 Hz, 1H), 3.29 (dt, J ) 9.5, 6.5 Hz, 1H),

2.52-2.58 (m, 4H), 2.08 (s, 3H), 1.82-1.93 (m, 2H), 1.25 (d, J

) 6.5 Hz, 3H), 1.17-1.24 (m, 4H), 1.06 (s, 9H), 0.95-0.99 (m,

2H); ¹³C NMR (125 MHz, CDCl₃) δ 206.0, 173.7, 171.8, 159.4,

159.0, 139.3, 139.2, 138.9, 137.8, 135.6, 135.5, 133.7, 133.3,

133.0, 130.1, 129.8, 129.7, 129.6, 128.9, 128.2, 128.1, 128.0,

127.7, 127.6, 127.3, 127.2, 127.1, 127.0, 123.2, 114.1, 113.6,

102.3, 98.0, 96.9, 81.43, 80.14, 80.05, 79.44, 78.18, 75.67, 75.24,

75.08, 74.84, 74.71, 73.67, 72.64, 72.37, 71.36, 70.91, 69.04,

66.71, 66.53, 66.38, 61.75, 56.11, 55.21, 55.21, 51.27, 38.20,

33.63, 29.66, 28.87, 28.21, 26.75, 25.27, 24.38, 19.10, 16.53;

2428 J . Org. Chem., Vol. 65, No. 8, 2000

Ye and Wong

removed by filtration, and the filtrate was concentrated. The

residue was subjected to a C-18 reversed-phase column chro-

matography (H₂O, H₂O-MeOH) to give 61 (10.7 mg, 84%) as

a solid after lyophilization: ¹H NMR (400 MHz, CD₃OD) δ

7.18-7.56 (m, 9H), 5.29 (dd, J ) 9.7, 8.0 Hz, 1H), 4.96 (d, J )

8.6 Hz, 1H), 4.87 (d, J ) 3.8 Hz, 1H), 4.70 (d, J ) 8.0 Hz, 1H),

4.50 (dd, J ) 10.8, 8.0 Hz, 1H), 4.04 (d, J ) 3.2 Hz, 1H), 4.01

(dd, J ) 10.8, 8.5 Hz, 1H), 3.89-3.95 (m, 2H), 3.88 (dd, J )

11.0, 8.0 Hz, 1H), 3.69-3.78 (m, 4H), 3.60 (dd, J ) 9.8, 8.0

Hz, 1H), 3.56 (s, 3H), 3.41-3.46 (m, 1H), 3.26-3.38 (m, 3H),

3.16 (t, J ) 9.0 Hz, 1H), 3.02 (dd, J ) 11.8, 3.3 Hz, 1H), 2.97

(dt, J ) 9.9, 3.0 Hz, 1H), 2.79 (dd, J ) 11.8, 2.0 Hz, 1H), 1.72-

1.89 (m, 2H), 1.10-1.33 (m, 4H), 0.80-0.96 (m, 2H); ¹³C NMR

(100 MHz, CD₃OD) δ 175.49, 166.51, 163.20, 157.86, 135.57,

134.26, 132.18, 130.67, 130.48, 129.61, 124.35, 123.89, 102.45,

99.42, 98.15, 83.00, 79.26, 77.77, 76.59, 74.59, 73.68, 73.06,

72.53, 71.52, 70.13, 70.09, 66.70, 62.66, 62.32, 60.96, 56.46,

51.90, 34.42, 29.88, 26.40, 25.29; HRMS (M + Cs) calcd for

C₄₀H₅₁O₂₀NCs 998.2059, found 998.2020.

5-Meth oxyca r bon ylp en tyl 2-Deoxy-2-a cetyla m in o-3-O-

(3-O-r-^D-glu cop yr a n osyl-â-D-ga la ct op yr a n osyl)-â-D-glu -

cop yr a n osid e (62). A mixture of 60 (28.0 mg, 0.0228 mmol)

and hydrazine acetate (21.0 mg, 0.228 mmol) in dry MeOH (4

mL) was boiled under reflux for 36 h. The solvent was then

evaporated. A solution of the residue in pyridine (1 mL) and

acetic anhydride (1 mL) was kept for 16 h at room tempera-

ture, methanol (1 mL) was added at 0 °C, the solvent was

evaporated, and toluene (2 × 10 mL) was evaporated from the

residue. A solution of the residue in CH₂Cl₂(20 mL) was

washed with saturated NaHCO₃and cold water and then

concentrated. Column chromatography (silica gel, hexanes/

EtOAc 1:1) of the residue gave a syrup.

The above syrup was treated with NaOMe/MeOH (25 wt

%, 0.1 mL) in MeOH (4 mL) at room temperature. After 24 h,

the mixture was neutralized (IRC-50 resin, weak acid) and

concentrated. The residue was purified by column chromatog-

raphy on silica gel (EtOAc/MeOH 4:1) to give a thick oil.

A mixture of above thick oil and 10% Pd-C (5.0 mg) in

HOAc (2.0 mL), THF (1.0 mL), and H₂O (0.5 mL) was stirred

overnight under H₂atmosphere. The catalyst was then re-

moved by filtration through Celite, and the filtrate was

concentrated. The residue was subjected to a C-18 reversed-

phase column chromatography (H₂O, H₂O-MeOH) to give 62

(5.4 mg, 35%) as a solid after lyophilization: ¹H NMR (400

MHz, D₂O) δ 4.96 (d, J ) 3.7 Hz, 1H), 4.41 (d, J ) 8.2 Hz,

1H), 4.34 (d, J ) 7.7 Hz, 1H), 4.02 (d, J ) 3.0 Hz, 1H), 3.32-

3.85 (m, 22H), 2.26 (t, J ) 7.4 Hz, 2H), 1.87 (s, 3H), 1.37-

1.51 (m, 4H), 1.16-1.25 (m, 2H); ¹³C NMR (100 MHz, CD₃OD)

δ 175.90, 174.18, 105.62, 102.41, 97.67, 85.01, 79.91, 77.55,

76.69, 75.04, 73.55, 73.41, 71.50, 70.66, 70.52, 70.33, 66.74,

62.69, 62.46, 62.42, 56.21, 51.99, 34.77, 30.25, 26.65, 25.72,

23.19; HRMS (M + Na) calcd for C₂₇H₄₇O₁₈NNa 696.2691,

found 696.2660; ESI-MS (pos) (M + Na) calcd 696, found 696;

ESI-MS (neg) (M - H) calcd 672, found 672.

Sa cch a r id e 63. This compound was prepared from hydro-

genolysis of 6d (46.0 mg, 0.05665 mmol) as described in the

preparation of 61, yielding 63 (25.6 mg, 99%) as a solid after

lyophilization: ¹H NMR (400 MHz, D₂O) δ 5.06 (d, J ) 3.8

Hz, 1H), 4.28 (d, J ) 7.8 Hz, 1H), 4.14 (q, J ) 6.5 Hz, 1H),

3.44-3.75 (m, 13H), 3.39 (dd, J ) 9.2, 8.0 Hz, 1H), 2.21 (t, J

) 7.4 Hz, 2H), 1.40-1.47 (m, 4H), 1.13-1.21 (m, 2H), 1.02 (d,

J ) 6.5 Hz, 3H); ¹³C NMR (100 MHz, D₂O) δ 179.95, 103.90,

101.76, 78.94, 77.40, 76.25, 74.31, 72.67, 71.96, 71.39, 70.72,

69.19, 63.33, 54.50, 36.03, 31.03, 27.27, 26.52, 17.85; HRMS

(M + Na) calcd for C₁₉H₃₄O₁₂Na 477.1948, found 477.1939.

Sa cch a r id e 64. This compound was prepared from the

corresponding fully protected saccharide 53 (36.0 mg, 0.02178

mmol) as described in the preparation of 62, yielding 64 (6.1

mg, 37%) as a solid after lyophilization. For the â-isomer: ¹H

NMR (400 MHz, D₂O) δ 7.68-7.80 (m, 4H), 5.10 (d, J ) 8.5

Hz, 1H), 4.31 (d, J ) 7.7 Hz, 1H), 4.30 (dd, J ) 9.7, 8.0 Hz,

1H), 4.29 (d, J ) 8.0 Hz, 1H), 3.32-3.87 (m, 21H), 3.24 (dd, J

) 10.0, 8.0 Hz, 1H), 1.51-1.72 (m, 2H), 1.14-1.25 (m, 2H),

0.91-1.07 (m, 2H), 0.69-0.80 (m, 2H); HRMS (M + Cs) calcd

for C₃₃H₄₇O₁₉NCs 894.1797, found 894.1830.

Sa cch a r id e 65. This compound was prepared from the

corresponding fully protected saccharide 52 (45.0 mg, 0.02722

mmol) as described in the preparation of 62, yielding 65 (7.5

mg, 36%) as a solid after lyophilization: ¹H NMR (400 MHz,

D₂O) δ 7.69-7.80 (m, 4H), 5.12 (d, J ) 8.6 Hz, 1H), 4.69 (d, J

) 2.6 Hz, 1H), 4.32 (d, J ) 7.8 Hz, 1H), 4.29 (dd, J ) 10.9, 8.0

Hz, 1H), 3.32-3.84 (m, 20H), 3.16 (dd, J ) 11.6, 4.5 Hz, 1H),

3.12 (m, 1H), 1.66-1.74 (m, 1H), 1.53-1.61 (m, 1H), 1.16-

1.26 (m, 2H), 0.92-1.13 (m, 2H), 0.72-0.83 (m, 2H); ¹³C NMR

(100 MHz, D₂O) δ 179.39, 172.24, 172.04, 137.97, 132.95,

132.85, 126.73, 126.09, 105.73, 101.13, 100.22, 83.20, 77.14,

76.27, 74.75, 73.29, 73.08, 72.57, 72.01, 71.45, 71.45, 71.11,

70.82, 70.05, 63.29, 62.61, 58.32, 54.41, 35.71, 30.49, 27.20,

26.01; ESI-MS (pos) (M + Na) calcd for C₃₃H₄₇O₁₉NNa 784,

found 784; ESI-MS (neg) (M - H) calcd 760, found 760.

Sa cch a r id e 66. This compound was prepared from the

corresponding fully protected saccharide 31 (22.5 mg, 0.01340

mmol) as described in the preparation of 62, yielding 66 (2.4

mg, 27%) as a solid after lyophilization: ¹H NMR (400 MHz,

CD₃OD) δ 5.01 (d, J ) 2.4 Hz, 1H), 4.44 (d, J ) 8.4 Hz, 1H),

4.33 (d, J ) 7.4 Hz, 1H), 4.29 (t, J ) 5.8 Hz, 1H), 3.29-4.01

(m, 22H), 2.32 (t, J ) 7.4 Hz, 2H), 1.96 (s, 3H), 1.31-1.65 (m,

4H), 0.81-0.95 (m, 2H); ESI-MS (pos) (M + Na) calcd for

C

₂₇H₄₇O₁₈NNa 696, found 696; ESI-MS (neg) (M - H) calcd

672, found 672.

Sa cch a r id e 67. This compound was prepared from the

corresponding fully protected saccharide 51 (67.7 mg, 0.04337

mmol) as described in the preparation of 62, yielding 67 (18.8

mg, 50%) as a solid after lyophilization: ¹H NMR (400 MHz,

D₂O) δ 7.14-7.43 (m, 7H), 7.04 (t, J ) 7.8 Hz, 2H), 4.90 (dd,

J ) 10.0, 8.0 Hz, 1H), 4.88 (d, J ) 8.6 Hz, 1H), 4.82 (d, J )

4.0 Hz, 1H), 4.66 (d, J ) 8.1 Hz, 1H), 4.40 (dd, J ) 10.9, 8.0

Hz, 1H), 3.44-3.94 (m, 17H), 3.39 (s, 3H), 3.20-3.25 (m, 1H),

1.52-1.60 (m, 1H), 1.36-1.44 (m, 1H), 0.40-1.10 (m, 6H); ¹³

C

NMR (100 MHz, D₂O) δ 179.27, 172.51, 171.88, 169.45, 137.94,

137.92, 136.57, 131.97, 131.63, 131.33, 130.14, 126.18, 125.77,

103.57, 101.10, 100.31, 84.15, 77.69, 76.22, 75.36, 73.60, 73.29,

72.42, 72.34, 71.67, 71.67, 70.89, 70.80, 69.29, 63.61, 63.12,

57.39, 54.37, 35.59, 30.43, 27.04, 25.80; HRMS (M + Cs) calcd

for C₄₀H₅₁O₂₀NCs 998.2059, found 998.2022.

Sa cch a r id e 68. This compound was prepared from the

corresponding fully protected saccharide 57 (35.0 mg, 0.02082

mmol) as described in the preparation of 62, yielding 68 (12.8

mg, 73%) as a solid after lyophilization: ¹H NMR (400 MHz,

D₂O) δ 7.66-7.74 (m, 4H), 5.12 (d, J ) 3.8 Hz, 1H), 5.09 (d, J

) 3.5 Hz, 1H), 5.02 (d, J ) 8.6 Hz, 1H), 4.50 (d, J ) 7.8 Hz,

1H), 4.20 (q, J ) 6.5 Hz, 1H), 4.15 (dd, J ) 10.7, 8.8 Hz, 1H),

4.02 (dd, J ) 10.8, 1.5 Hz, 1H), 3.90 (dd, J ) 9.7, 3.5 Hz, 1H),

3.82 (dd, J ) 12.5, 5.5 Hz, 1H), 3.73 (dd, J ) 10.7, 8.5 Hz,

1H), 3.54-3.71 (m, 6H), 3.51 (dd, J ) 9.6, 7.8 Hz, 1H), 3.42-

3.47 (m, 2H), 3.41 (s, 3H), 3.30-3.37 (m, 2H), 2.75 (t, J ) 6.0

Hz, 2H), 2.52 (t, J ) 6.5 Hz, 2H), 2.06 (s, 3H), 1.66-1.74 (m,

1H), 1.52-1.61 (m, 1H), 1.13-1.24 (m, 2H), 1.10 (d, J ) 6.5

Hz, 3H), 1.00-1.07 (m, 1H), 0.87-0.98 (m, 1H), 0.66-0.83 (m,

2H); ¹³C NMR (100 MHz, D₂O) δ 215.98, 179.32, 177.03,

172.49, 172.30, 137.76, 133.05, 126.41, 126.06, 104.46, 101.69,

100.46, 78.63, 77.93, 76.20, 74.67, 74.31, 73.95, 72.99, 72.94,

72.38, 71.95, 70.67, 70.51, 69.38, 62.70, 59.26, 54.42, 40.12,

35.71, 31.58, 30.56, 30.32, 27.23, 26.03, 18.03; HRMS (M +

Cs) calcd for C₃₈H₅₃O₂₀NCs 976.2215, found 976.2247.

Sa cch a r id e 69. This compound was prepared from the

corresponding fully protected saccharide 56 (36.0 mg, 0.02142

mmol) as described in the preparation of 62, yielding 69 (12.6

mg, 70%) as a solid after lyophilization: ¹H NMR (400 MHz,

D₂O) δ 7.67-7.75 (m, 4H), 5.21 (d, J ) 3.4 Hz, 1H), 5.04 (d, J

) 8.6 Hz, 1H), 4.99 (d, J ) 3.6 Hz, 1H), 4.89 (d, J ) 4.0 Hz,

1H), 4.14 (dd, J ) 10.7, 8.9 Hz, 1H), 4.07 (dd, J ) 10.2, 3.4

Hz, 1H), 4.02 (q, J ) 6.5 Hz, 1H), 3.97 (t, J ) 6.3 Hz, 1H),

3.87 (dd, J ) 11.1, 4.9 Hz, 1H), 3.78 (dd, J ) 10.8, 8.7 Hz,

1H), 3.75 (dd, J ) 11.2, 3.3 Hz, 1H), 3.33-3.71 (m, 13H), 2.75

(t, J ) 6.2 Hz, 2H), 2.50-2.54 (m, 2H), 2.05 (s, 3H), 1.66-1.75

(m, 1H), 1.53-1.61 (m, 1H), 1.12-1.24 (m, 2H), 1.08 (d, J )

6.5 Hz, 3H), 1.02-1.07 (m, 1H), 0.87-0.98 (m, 1H), 0.65-0.83

(m, 2H); ¹³C NMR (100 MHz, D₂O) δ 215.98, 179.33, 176.95,

172.52, 172.30, 137.74, 133.06, 126.39,126.04, 103.96, 100.46,

One-Pot Oligosaccharide Synthesis

J . Org. Chem., Vol. 65, No. 8, 2000 2429

100.35, 80.05, 77.10, 74.32, 74.20, 73.22, 72.79, 72.36, 72.11,

71.82, 70.71, 69.71, 69.38, 68.36, 62.78, 59.26, 54.42, 40.10,

35.71, 31.54, 30.56, 30.32, 27.22, 26.04, 18.17; HRMS (M +

Cs) calcd for C₃₈H₅₃O₂₀NCs 976.2215, found 976.2249.

Sa cch a r id e 70. This compound was prepared from hydro-

genolysis of 5-methoxycarbonylpentyl 2-deoxy-2-phthalimido-

3-O-benzyl-4-O-(2,3,4-tri-O-benzyl-R-^L-fucopyranosyl)-6-O-p-

methoxybenzyl-â-^D-glucopyranoside (53.0 mg, 0.04986 mmol)

isolated as a side product like the formation of 13 in the

assembly of oligosaccharides, yielding 70 (23.3 mg, 80%) as a

solid after lyophilization: ¹H NMR (400 MHz, CD₃OD) δ 7.81-

7.88 (m, 4H), 5.14 (d, J ) 8.6 Hz, 1H), 5.00 (d, J ) 3.7 Hz,

1H), 4.36 (dd, J ) 10.7, 8.6 Hz, 1H), 4.28 (q, J ) 6.5 Hz, 1H),

4.02 (dd, J ) 10.7, 8.6 Hz, 1H), 3.62-3.97 (m, 7H), 3.59 (s,

3H), 3.55 (dt, J ) 9.7, 3.1 Hz, 1H), 3.39-3.46 (m, 1H), 1.86-

2.00 (m, 2H), 1.25-1.46 (m, 4H), 1.14 (d, J ) 6.6 Hz, 3H),

1.01-1.12 (m, 2H); ¹³C NMR (100 MHz, CD₃OD) δ 175.54,

169.92, 169.48, 135.64, 132.96, 124.38, 124.16, 101.66, 99.62,

80.45, 77.05, 73.70, 71.46, 71.34, 70.17, 69.98, 68.24, 61.95,

58.75, 51.92, 34.40, 29.98, 26.50, 25.34, 16.50; HRMS (M +

Cs) calcd for C₂₇H₃₇O₁₃NCs 716.1319, found 716.1342.

Sa cch a r id e 71. This compound was prepared from the

corresponding fully protected saccharide 47 (75.0 mg, 0.04446

mmol) as described in the preparation of 62, yielding 71 (22.4

mg, 59%) as a solid after lyophilization: ¹H NMR (400 MHz,

CD₃OD) δ 8.00 (dd, J ) 8.2, 1.0 Hz, 2H), 7.69-7.75 (m, 4H),

7.52 (tt, J ) 7.4, 1.2 Hz, 1H), 7.40 (t, J ) 7.5 Hz, 2H), 5.21

(dd, J ) 9.8, 8.1 Hz, 1H), 4.98 (d, J ) 8.5 Hz, 1H), 4.86 (d, J

) 3.4 Hz, 1H), 4.69 (d, J ) 8.1 Hz, 1H), 4.26 (dd, J ) 10.8, 8.5

Hz, 1H), 4.01 (q, J ) 6.5 Hz, 1H), 3.88 (dd, J ) 10.9, 8.6 Hz,

1H), 3.86 (d, J ) 3.7 Hz, 1H), 3.82 (dd, J ) 9.8, 3.3 Hz, 1H),

3.58-3.76 (m, 8H), 3.46-3.53 (m, 2H), 3.45 (s, 3H), 3.19-3.29

(m, 2H), 1.73-1.87 (m, 2H), 1.15-1.29 (m, 4H), 1.09 (d, J )

6.5 Hz, 3H), 0.88-0.97 (m, 2H); ¹³C NMR (100 MHz, CD₃OD)

δ 175.57, 169.73, 169.41, 167.31, 135.68, 134.49, 132.89,

131.16, 130.80, 129.67, 124.41, 124.20, 104.44, 102.57, 99.50,

81.73, 81.19, 77.33, 76.54, 74.97, 73.70, 73.50, 71.62, 70.98,

70.65, 70.20, 68.82, 62.80, 61.25, 57.87, 51.93, 34.48, 29.94,

26.47, 25.38, 16.62; HRMS (M + Cs) calcd for C₄₀H₅₁O₁₉NCs

982.2110, found 982.2139.

Sa cch a r id e 72. This compound was prepared from the

corresponding fully protected saccharide 41 (35.0 mg, 0.02194

mmol) as described in the preparation of 62, yielding 72 (12.7

mg, 68%) as a solid after lyophilization: ¹H NMR (500 MHz,

CD₃OD) δ 7.41-7.43 (m, 4H), 7.35 (t, J ) 7.5 Hz, 1H), 7.30

(m, 1H), 7.18 (m, 1H), 7.08 (t, J ) 7.5 Hz, 2H), 5.04 (dd, J )

9.5, 8.0 Hz, 1H), 4.87 (d, J ) 8.5 Hz, 1H), 4.80 (d, J ) 3.5 Hz,

1H), 4.56 (d, J ) 8.0 Hz, 1H), 4.37 (dd, J ) 10.5, 8.0 Hz, 1H),

4.04 (q, J ) 6.5 Hz, 1H), 3.91 (dd, J ) 10.5, 8.5 Hz, 1H), 3.82

(dd, J ) 11.5, 1.5 Hz, 1H), 3.79 (d, J ) 3.0 Hz, 1H), 3.75 (dd,

J ) 10.5, 3.5 Hz, 1H), 3.62-3.69 (m, 8H), 3.50 (dd, J ) 9.5,

8.0 Hz, 1H), 3.46 (s, 3H), 3.32-3.35 (m, 1H), 3.19-3.24 (m,

1H), 1.63-1.76 (m, 2H), 1.14 (d, J ) 6.5 Hz, 3H), 1.04-1.23

(m, 4H), 0.74-0.84 (m, 2H); ¹³C NMR (125 MHz, CD₃OD) δ

175.5, 170.0, 168.9, 166.8, 135.5, 134.1, 132.1, 130.7, 130.4,

129.5, 124.3, 123.8, 104.5, 102.5, 99.4, 83.31, 81.49, 77.77,

76.94, 75.12, 73.70, 73.53, 71.57, 71.50, 70.64, 70.11, 68.87,

62.62, 62.59, 56.42, 51.90, 34.42, 29.88, 26.40, 25.29, 16.66;

HRMS (M + Cs) calcd for C₄₀H₅₁O₁₉NCs 982.2110, found

982.2141.

99.40, 96.26, 83.25, 77.74, 76.82, 76.53, 72.40, 72.05, 71.59,

71.03, 70.86, 70.09, 69.71, 65.55, 62.72, 62.67, 62.34, 56.43,

51.89, 34.42, 29.88, 26.41, 25.29; HRMS (M + Cs) calcd for

C₄₀H₅₁O₂₀NCs 998.2059, found 998.2030.

Sa cch a r id e 74. This compound was prepared from hydro-

genolysis of 5-methoxycarbonylpentyl 2-deoxy-2-phthalimido-

3-O-(2,3,4,6-tetra-O-benzyl-R-^D-galactopyranosyl)-4,6-O-p-meth-

oxybenzylidene-â-^D-glucopyranoside (70.0 mg, 0.06500 mmol)

isolated as a side product like the formation of 13 in the

assembly of oligosaccharides, yielding 74 (26.7 mg, 69%) as a

solid after lyophilization: ¹H NMR (400 MHz, CD₃OD) δ 7.79-

7.92 (m, 4H), 5.14 (d, J ) 8.4 Hz, 1H), 4.90 (d, J ) 3.8 Hz,

1H), 4.37 (dd, J ) 10.8, 8.6 Hz, 1H), 4.07 (dd, J ) 10.8, 8.5

Hz, 1H), 3.91 (dd, J ) 12.0, 2.1 Hz, 1H), 3.60-3.87 (m, 6H),

3.59 (s, 3H), 3.40-3.54 (m, 3H), 3.14 (dd, J ) 10.4, 8.1 Hz,

1H), 2.67 (dd, J ) 10.4, 4.8 Hz, 1H), 1.84-1.99 (m, 2H), 1.24-

1.44 (m, 4H), 1.02-1.15 (m, 2H); ¹³C NMR (100 MHz, CD₃-

OD) δ 175.54, 170.04, 169.45, 135.78, 132.92, 124.64, 124.35,

104.03, 99.68, 83.95, 77.67, 72.56, 72.37, 71.17, 70.71, 70.22,

70.22, 62.39, 60.84, 56.93, 51.92, 34.48, 29.96, 26.50, 25.40;

HRMS (M + Cs) calcd for C₂₇H₃₇O₁₄NCs 732.1268, found

732.1244.

Sa cch a r id e 75. This compound was prepared from hydro-

genolysis of 5-methoxycarbonylpentyl 2-deoxy-2-phthalimido-

3-O-(2,3,4,6-tetra-O-benzyl-^D-glucopyranosyl)-4,6-O-p-meth-

oxybenzylidene-â-^D-glucopyranoside (36.0 mg, 0.03343 mmol)

isolated as a side product like the formation of 13 in the

assembly of oligosaccharides, yielding 75 (18.4 mg, 92%) as a

solid after lyophilization: ¹H NMR (400 MHz, CD₃OD) R/â )

3:1, for R-isomer, δ 7.85-7.91 (m, 4H), 5.14 (d, J ) 8.4 Hz,

1H), 4.92 (d, J ) 3.7 Hz, 1H), 4.37 (dd, J ) 10.8, 8.6 Hz, 1H),

3.01-4.13 (m, 15H), 2.53 (dd, J ) 11.8, 2.2 Hz, 1H), 1.84-

1.99 (m, 2H), 1.24-1.46 (m, 4H), 1.00-1.13 (m, 2H); HRMS

(M + Cs) calcd for C₂₇H₃₇O₁₄NCs 732.1268, found 732.1245.

Sa cch a r id e 76. This compound was prepared from hydro-

genolysis of 5-methoxycarbonylpentyl 2-deoxy-2-phthalimido-

3-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-R-^D-glucopyranosyl)-6-

O-p-methoxybenzyl-â-^D-glucopyranoside (11.0 mg, 0.00941

mmol) isolated as a side product like the formation of 13 in

the assembly of oligosaccharides, yielding 76 (4.6 mg, 82%)

as a solid after lyophilization: ¹H NMR (400 MHz, CD₃OD) δ

7.81-7.89 (m, 4H), 5.24 (d, J ) 3.8 Hz, 1H), 5.16 (d, J ) 8.5

Hz, 1H), 4.51 (dd, J ) 10.9, 8.6 Hz, 1H), 4.01 (dd, J ) 11.1,

8.5 Hz, 1H), 3.24-3.96 (m, 15H), 1.84-2.00 (m, 2H), 1.25-

1.45 (m, 4H), 1.02-1.13 (m, 2H); ESI-MS (pos) (M + Na) calcd

for C₂₇H₃₇O₁₄NNa 622, found 622; ESI-MS (neg) (M - H) calcd

598, found 598.

Sa cch a r id e 77. This compound was prepared from the

corresponding fully protected saccharide 40 (22.0 mg, 0.01321

mmol) as described in the preparation of 62, yielding 77 (8.2

mg, 66%) as a solid after lyophilization: ¹H NMR (500 MHz,

CD₃OD) δ 7.99 (dd, J ) 8.5, 1.0 Hz, 2H), 7.80-7.86 (m, 4H),

7.61 (t, J ) 7.5 Hz, 1H), 7.49 (t, J ) 7.5 Hz, 2H), 5.54 (dd, J

) 10.5, 8.0 Hz, 1H), 5.28 (dd, J ) 10.5, 3.0 Hz, 1H), 5.16 (d, J

) 4.0 Hz, 1H), 4.95 (d, J ) 8.5 Hz, 1H), 4.92 (d, J ) 7.5 Hz,

1H), 4.29 (s, 1H), 4.28 (dd, J ) 9.5, 1.0 Hz, 1H), 4.14 (dd, J )

10.5, 7.5 Hz, 1H), 4.07 (q, J ) 6.5 Hz, 1H), 3.72-3.87 (m, 8H),

3.59 (s, 3H), 3.40-3.52 (m, 2H), 3.19 (dd, J ) 9.5, 8.5 Hz, 1H),

3.06-3.10 (m, 1H), 2.64-2.67 (m, 2H), 2.46-2.52 (m, 1H),

2.37-2.43 (m, 1H), 1.95 (s, 3H), 1.85-1.94 (m, 2H), 1.24-1.31

(m, 2H), 1.22 (d, J ) 6.5 Hz, 3H), 1.13-1.20 (m, 2H), 0.91-

0.97 (m, 2H); ¹³C NMR (125 MHz, CD₃OD) δ 208.9, 175.6,

173.4, 167.1, 135.6, 134.6, 133.0, 131.1, 130.9, 129.7, 124.3,

124.1, 103.0, 101.6, 99.3, 77.60, 76.84, 75.35, 74.18, 73.60,

72.93, 72.51, 71.75, 71.65, 70.51, 70.51, 69.86, 68.65, 62.06,

58.43, 51.96, 38.54, 24.60, 29.84, 29.41, 29.04, 26.47, 25.42,

16.66; HRMS (M + Cs) calcd for C₄₅H₅₇O₂₁NCs 1080.2477,

found 1080.2448.

Sa cch a r id e 73. This compound was prepared from the

corresponding fully protected saccharide 31 (33.0 mg, 0.01965

mmol) as described in the preparation of 62, yielding 73 (11.1

mg, 65%) as a solid after lyophilization: ¹H NMR (400 MHz,

CD₃OD) δ 7.59 (dd, J ) 8.2, 1.1 Hz, 2H), 7.45-7.54 (m, 4H),

7.24-7.28 (m, 2H), 7.21 (t, J ) 8.0 Hz, 2H), 5.35 (dd, J ) 10.0,

8.0 Hz, 1H), 4.98 (d, J ) 8.6 Hz, 1H), 4.96 (d, J ) 3.8 Hz, 1H),

4.73 (d, J ) 8.0 Hz, 1H), 4.49 (dd, J ) 10.8, 8.0 Hz, 1H), 4.10

(d, J ) 2.9 Hz, 1H), 3.98-4.04 (m, 2H), 3.93 (dd, J ) 12.0, 2.0

Hz, 1H), 3.87 (dd, J ) 11.2, 8.2 Hz, 1H), 3.58-3.79 (m, 6H),

3.56 (s, 3H), 3.28-3.47 (m, 4H), 3.24 (dd, J ) 10.1, 3.3 Hz,

1H), 3.11 (dd, J ) 11.0, 4.0 Hz, 1H), 3.06-3.07 (m, 1H), 1.72-

1.88 (m, 2H), 1.10-1.34 (m, 4H), 0.81-0.97 (m, 2H); ¹³C NMR

(100 MHz, CD₃OD) δ 175.49, 170.01, 168.85, 166.44, 135.55,

134.33, 132.18, 130.70, 130.27, 129.67, 124.31, 123.85, 102.50,

Sa cch a r id e 78. This compound was prepared from the

corresponding fully protected saccharide 39 (40.4 mg, 0.02426

mmol) as described in the preparation of 62, yielding 78 (7.1

mg, 39%) as a solid after lyophilization: ¹H NMR (500 MHz,

D₂O) δ 7.73-7.80 (m, 4H), 5.13 (d, J ) 8.5 Hz, 1H), 5.03 (d, J

) 4.0 Hz, 1H), 4.40 (d, J ) 7.5 Hz, 1H), 4.21 (dd, J ) 10.5, 9.5

Hz, 1H), 4.15 (d, J ) 11.5 Hz, 1H), 4.05 (q, J ) 6.5 Hz, 1H),

2430 J . Org. Chem., Vol. 65, No. 8, 2000

Ye and Wong

3.41-3.89 (m, 18H), 1.70-1.76 (m, 1H), 1.56-1.63 (m, 1H),

1.16-1.28 (m, 2H), 1.07-1.13 (m, 1H), 1.06 (d, J ) 6.5 Hz,

3H), 0.94-1.01 (m, 1H), 0.74-0.86 (m, 2H); ¹³C NMR (125

MHz, D₂O) δ 177.7, 170.8, 170.7, 136.1, 131.4, 124.7, 124.4,

104.0, 101.7, 98.9, 81.52, 75.94, 75.88, 72.55, 71.32, 71.13,

70.93, 70.93, 70.19, 69.44, 69.40, 69.25, 67.98, 61.69, 57.59,

52.76, 34.04, 28.88, 25.54, 24.35, 16.12; HRMS (M + Cs) calcd

for C₃₃H₄₇O₁₈NCs 878.1847, found 878.1868.

Sa cch a r id e 79. This compound was prepared from the

corresponding fully protected saccharide 38 (36.6 mg, 0.02067

mmol) as described in the preparation of 62, yielding 79 (6.6

mg, 42%) as a solid after lyophilization: ¹H NMR (400 MHz,

D₂O) δ 7.71-7.79 (m, 4H), 5.12 (d, J ) 8.6 Hz, 1H), 4.96 (d, J

) 3.6 Hz, 1H), 4.37 (d, J ) 7.7 Hz, 1H), 4.20 (dd, J ) 10.0, 9.5

Hz, 1H), 4.14 (d, J ) 11.5 Hz, 1H), 4.02 (d, J ) 2.4 Hz, 1H),

3.38-3.87 (m, 19H), 3.31 (t, J ) 9.5 Hz, 1H), 1.68-1.76 (m,

1H), 1.53-1.62 (m, 1H), 1.16-1.28 (m, 2H), 1.03-1.14 (m, 1H),

0.90-1.01 (m, 1H), 0.68-0.87 (m, 2H); ¹³C NMR (100 MHz,

D₂O) δ 179.37, 173.58, 172.71, 137.75, 133.03, 126.40, 126.05,

105.86, 100.52, 97.84, 79.88, 77.54, 77.31, 75.26, 74.14, 73.78,

72.96, 72.71, 72.57, 71.74, 71.61, 71.09, 67.44, 63.38, 62.64,

59.23, 54.41, 35.69, 30.53, 27.19, 26.00; HRMS (M + Cs) calcd

for C₃₃H₄₇O₁₉NCs 894.1797, found 894.1766.

J ) 7.5 Hz, 1H), 7.53 (t, J ) 7.5 Hz, 2H), 5.49 (dd, J ) 9.5, 8.1

Hz, 1H), 5.08 (d, J ) 8.5 Hz, 1H), 5.06 (d, J ) 3.7 Hz, 1H),

4.88 (d, J ) 8.0 Hz, 1H), 4.38 (dd, J ) 10.8, 8.6 Hz, 1H), 4.15

(s, 1H), 4.14 (dd, J ) 11.5, 3.0 Hz, 1H), 3.99 (dd, J ) 10.9, 8.6

Hz, 1H), 3.84 (dd, J ) 12.3, 8.8 Hz, 1H), 3.57-3.78 (m, 8H),

3.56 (s, 3H), 3.45-3.51 (m, 2H), 3.31-3.40 (m, 4H), 1.84-1.98

(m, 2H), 1.22-1.42 (m, 4H), 0.98-1.12 (m, 2H); ¹³C NMR (125

MHz, CD₃OD) δ 175.6, 169.8, 169.4, 167.0, 135.7, 134.8, 132.9,

131.0, 130.8, 129.9, 124.4, 124.2, 102.4, 99.6, 96.7, 80.74, 77.13,

76.69, 76.58, 72.40, 72.29, 71.17, 71.08, 70.97, 70.21, 69.82,

66.12, 62.86, 62.54, 61.22, 57.77, 51.91, 34.49, 29.95, 26.48,

25.39; ESI-MS (pos) (M + Na) calcd for C₄₀H₅₁O₂₀NNa 888,

found 888; ESI-MS (neg) (M - H) calcd 864, found 864.

Sa cch a r id e 84. This compound was prepared from the

corresponding fully protected saccharide 54 (70.0 mg, 0.04235

mmol) as described in the preparation of 62, yielding 84 (18.1

mg, 56%) as a solid after lyophilization: ¹H NMR (400 MHz,

D₂O) δ 7.69-7.77 (m, 4H), 5.08 (d, J ) 8.6 Hz, 1H), 4.83 (d, J

) 3.4 Hz, 1H), 4.33 (d, J ) 7.8 Hz, 1H), 4.17 (dd, J ) 10.8, 8.9

Hz, 1H), 4.08 (dd, J ) 11.4, 1.5 Hz, 1H), 3.37-3.85 (m, 21H),

1.66-1.74 (m, 1H), 1.53-1.60 (m, 1H), 1.13-1.26 (m, 2H),

1.01-1.11 (m, 1H), 0.89-1.00 (m, 1H), 0.66-0.85 (m, 2H); ¹³

C

NMR (100 MHz, D₂O) δ 179.36, 172.50, 172.33, 137.77, 133.08,

126.41, 126.07, 105.91, 100.69, 100.54, 77.73, 75.50, 75.08,

73.42, 73.17, 73.00, 72.88, 72.62, 71.89, 71.67, 71.26, 71.12,

70.68, 68.74, 63.64, 59.23, 54.42, 35.70, 30.55, 27.21, 26.02;

HRMS (M + Cs) calcd for C₃₃H₄₇O₁₉NCs 894.1797, found

894.1771.

Sa cch a r id e 80. This compound was prepared from hydro-

genolysis of 5-methoxycarbonylpentyl 2-deoxy-2-phthalimido-

3-O-(2,3,4-tri-O-benzyl-^L-fucopyranosyl)-4,6-O-p-methoxy-

benzylidene-â-^D-glucopyranoside (13) (58.0 mg, 0.05973 mmol),

yielding 80 (23.2 mg, 67%) as a solid after lyophilization: ¹H

NMR (400 MHz, CD₃OD) R/â ) 9:2, for R-isomer, δ 7.79-7.87

(m, 4H), 5.10 (d, J ) 8.5 Hz, 1H), 4.65 (d, J ) 4.0 Hz, 1H),

4.36 (dd, J ) 10.8, 8.2 Hz, 1H), 4.20 (q, J ) 6.5 Hz, 1H), 4.11

(dd, J ) 10.8, 8.5 Hz, 1H), 3.33-3.95 (m, 12H), 1.84-1.99 (m,

2H), 1.24-1.46 (m, 4H), 1.15 (d, J ) 6.6 Hz, 3H), 0.99-1.10

(m, 2H); ¹³C NMR (100 MHz, CD₃OD) δ 175.55, 170.36, 169.58,

135.49, 133.31, 124.49, 124.19, 102.07, 99.72, 81.32, 78.11,

73.47, 71.41, 71.17, 70.23, 69.29, 68.49, 62.54, 56.83, 51.93,

34.50, 29.99, 26.51, 25.41, 16.51; HRMS (M + Cs) calcd for

Sa cch a r id e 85. This compound was prepared from hydro-

genolysis of 5-methoxycarbonylpentyl 2-deoxy-2-phthalimido-

3-O-benzyl-4-O-p-methoxybenzyl-6-O-(2,3,4-tri-O-benzyl-R-L-

fucopyranosyl)-â-^D-glucopyranoside (30.4 mg, 0.02860 mmol)

isolated as a side product like the formation of 13 in the

assembly of oligosaccharides, yielding 85 (8.6 mg, 52%) as a

solid after lyophilization: ¹H NMR (500 MHz, CD₃OD) δ 7.81-

7.88 (m, 4H), 5.15 (d, J ) 8.5 Hz, 1H), 4.85 (d, J ) 3.5 Hz,

1H), 4.25 (dd, J ) 10.5, 8.5 Hz, 1H), 4.12 (q, J ) 6.5 Hz, 1H),

3.77-3.99 (m, 5H), 3.75 (dd, J ) 10.0, 3.5 Hz, 1H), 3.68-3.69

(m, 1H), 3.59 (s, 3H), 3.55-3.58 (m, 1H), 3.50 (dd, J ) 9.5, 9.0

Hz, 1H), 3.41-3.45 (m, 1H), 1.88-2.00 (m, 2H), 1.29-1.47 (m,

4H), 1.22 (d, J ) 6.5 Hz, 3H), 1.03-1.13 (m, 2H); ¹³C NMR

(125 MHz, CD₃OD) δ 175.6, 170.0, 169.6, 135.6, 133.1, 124.4,

124.1, 100.9, 99.7, 77.09, 73.67, 72.30, 72.23, 71.75, 70.18,

70.18, 68.03, 67.62, 58.64, 51.95, 34.53, 30.04, 26.56, 25.48,

16.72; HRMS (M + Cs) calcd for C₂₇H₃₇O₁₃NCs 716.1319, found

716.1341.

C

₂₇H₃₇O₁₃NCs 716.1319, found 716.1343.

Sa cch a r id e 81. This compound was prepared from hydro-

genolysis of 5-methoxycarbonylpentyl 2-deoxy-2-phthalimido-

3-O-benzyl-4-O-p-methoxybenzyl-6-O-(2,3,4,6-tetra-O-benzyl-

D-glucopyranosyl)-â-D-glucopyranoside (30.4 mg, 0.02601 mmol)

isolated as a side product like the formation of 13 in the

assembly of oligosaccharides, yielding 81 (8.5 mg, 55%) as a

solid after lyophilization: ¹H NMR (400 MHz, CD₃OD) R/â )

1:1, δ 7.81-7.88 (m, 8H), 5.17 (d, J ) 8.6 Hz, 1H), 5.15 (d, J

) 8.6 Hz, 1H), 4.88 (d, J ) 3.8 Hz, 1H), 4.41 (d, J ) 7.7 Hz,

1H), 3.60-4.28 (m, 18H), 3.59 (s, 6H), 3.22-3.56 (m, 10H),

1.85-2.00 (m, 4H), 1.24-1.48 (m,8H), 1.01-1.13 (m, 4H);

HRMS (M + Cs) calcd for C₂₇H₃₇O₁₄NCs 732.1268, found

732.1245.

Sa cch a r id e 86. This compound was prepared from the

corresponding fully protected saccharide 35 (69.6 mg, 0.04180

mmol) as described in the preparation of 62, yielding 86 (26.7

mg, 75%) as a solid after lyophilization: ¹H NMR (400 MHz,

CD₃OD) δ 8.09 (d, J ) 7.5 Hz, 2H), 7.81-7.86 (m, 4H), 7.62 (t,

J ) 7.4 Hz, 1H), 7.50 (t, J ) 7.5 Hz, 2H), 5.51 (dd, J ) 9.4, 8.0

Hz, 1H), 5.08 (d, J ) 8.5 Hz, 1H), 4.92 (d, J ) 4.0 Hz, 1H),

4.85 (d, J ) 8.0 Hz, 1H), 4.37 (dd, J ) 10.9, 8.6 Hz, 1H), 4.10

(q, J ) 6.5 Hz, 1H), 3.57-4.03 (m, 11H), 3.56 (s, 3H), 3.47-

3.55 (m, 2H), 3.27-3.39 (m, 2H), 1.83-1.97 (m, 2H), 1.24-

Sa cch a r id e 82. This compound was prepared from the

corresponding fully protected saccharide 34 (69.1 mg, 0.03902

mmol) as described in the preparation of 62, yielding 82 (25.2

mg, 75%) as a solid after lyophilization: ¹H NMR (400 MHz,

CD₃OD-CDCl₃v/v ) 1:1) δ 8.06 (d, J ) 7.5 Hz, 2H), 7.74-7.83

(m, 4H), 7.59 (t, J ) 7.5 Hz, 1H), 7.47 (t, J ) 7.6 Hz, 2H), 5.43

(dd, J ) 9.8, 8.1 Hz, 1H), 5.06 (d, J ) 8.5 Hz, 1H), 4.93 (d, J

) 3.8 Hz, 1H), 4.81 (d, J ) 8.0 Hz, 1H), 4.37 (dd, J ) 10.9, 8.6

Hz, 1H), 4.07 (d, J ) 2.8 Hz, 1H), 3.97-4.03 (m, 2H), 3.84 (dd,

J ) 10.8, 6.7 Hz, 1H), 3.44-3.79 (m, 10H), 3.21-3.38 (m, 6H),

3.19 (dd, J ) 11.4, 9.8 Hz, 1H), 1.86-1.99 (m, 2H), 1.26-1.39

(m, 4H), 0.97-1.09 (m, 2H); ¹³C NMR (100 MHz, CD₃OD-CDCl₃

v/v ) 1:1) δ 175.59, 169.23, 168.92, 166.54, 134.99, 134.23,

132.20, 130.37, 129.90, 129.21, 124.01, 123.78, 101.50, 98.81,

97.34, 79.40, 78.08, 76.24, 75.65, 73.99, 73.02, 72.35, 71.75,

70.20, 69.89, 69.79, 66.35, 62.08, 60.88, 60.44, 56.89, 51.86,

34.18, 29.38, 25.84, 24.85; ESI-MS (pos) (M + Na) calcd for

1.39 (m, 4H), 1.19 (d, J ) 6.5 Hz, 3H), 0.98-1.11 (m, 2H); ¹³

C

NMR (100 MHz, CD₃OD) δ 175.57, 169.77, 169.40, 167.41,

135.69, 134.49, 132.90, 131.15, 130.88, 129.70, 124.40, 124.23,

102.51, 102.40, 99.52, 80.47, 79.76, 77.29, 76.53, 73.54, 73.44,

71.46, 70.96, 70.39, 70.20, 69.86, 68.16, 62.35, 61.14, 57.79,

51.93, 34.48, 29.94, 26.47, 25.39, 16.66; HRMS (M + Cs) calcd

for C₄₀H₅₁O₁₉NCs 982.2110, found 982.2144.

Sa cch a r id e 87. This compound was prepared from the

corresponding fully protected saccharide 48 (50.0 mg, 0.02964

mmol) as described in the preparation of 62, yielding 87 (17.0

mg, 68%) as a solid after lyophilization: ¹H NMR (400 MHz,

CD₃OD) δ 7.68-7.94 (m, 6H), 7.49 (tt, J ) 7.4, 1.2 Hz, 1H),

7.37 (t, J ) 7.6 Hz, 2H), 5.17 (dd, J ) 10.0, 8.0 Hz, 1H), 4.89

(d, J ) 3.8 Hz, 1H), 4.86 (d, J ) 8.5 Hz, 1H), 4.64 (d, J ) 8.0

Hz, 1H), 4.16 (dd, J ) 11.2, 1.4 Hz, 1H), 4.09 (q, J ) 6.5 Hz,

1H), 4.05 (dd, J ) 10.7, 8.6 Hz, 1H), 3.91 (d, J ) 3.0 Hz, 1H),

3.81 (t, J ) 2.9 Hz, 1H), 3.78 (t, J ) 2.9 Hz, 1H), 3.54-3.76

(m, 7H), 3.48 (s, 3H), 3.40 (t, J ) 7.8 Hz, 1H), 3.28 (dt, J )

10.2, 5.9 Hz, 1H), 3.08 (dd, J ) 9.8, 8.7 Hz, 1H), 2.93-2.99

C

₄₀H₅₁O₂₀NNa 888, found 888; ESI-MS (neg) (M - H) calcd

864, found 864.

Sa cch a r id e 83. This compound was prepared from the

corresponding fully protected saccharide 33 (30.9 mg, 0.01745

mmol) as described in the preparation of 62, yielding 83 (12.8

mg, 85%) as a solid after lyophilization: ¹H NMR (400 MHz,

CD₃OD) δ 8.16 (d, J ) 7.5 Hz, 2H), 7.80-7.86 (m, 4H), 7.66 (t,

One-Pot Oligosaccharide Synthesis

J . Org. Chem., Vol. 65, No. 8, 2000 2431

(m, 1H), 1.70-1.84 (m, 2H), 1.15 (d, J ) 6.5 Hz, 3H), 0.98-

1.15 (m, 4H), 0.77-0.85 (m, 2H); ¹³C NMR (100 MHz, CD₃-

OD) δ 175.55, 169.88, 169.49, 167.55, 135.59, 134.31, 132.95,

131.59, 130.71, 129.62, 124.31, 124.14, 104.41, 102.81, 99.23,

81.84, 77.54, 76.75, 75.15, 73.66, 73.58, 73.00, 72.49, 71.68,

70.78, 70.36, 69.74, 68.87, 62.54, 58.42, 51.96, 34.49, 29.80,

26.45, 25.35, 16.69; HRMS (M + Cs) calcd for C₄₀H₅₁O₁₉NCs

982.2110, found 982.2088.

Sa cch a r id e 88. This compound was prepared from the

corresponding fully protected saccharide 36 (70.0 mg, 0.03952

mmol) as described in the preparation of 62, yielding 88 (24.9

mg, 73%) as a solid after lyophilization: ¹H NMR (400 MHz,

CD₃OD) δ 8.10 (dd, J ) 8.5, 1.4 Hz, 2H), 7.78-7.86 (m, 4H),

7.62 (t, J ) 7.5 Hz, 1H), 7.50 (t, J ) 7.9 Hz, 2H), 5.47 (dd, J

) 10.0, 8.0 Hz, 1H), 5.08 (d, J ) 3.7 Hz, 1H), 4.96 (d, J ) 8.5

Hz, 1H), 4.81 (d, J ) 8.0 Hz, 1H), 4.29 (dd, J ) 11.1, 1.3 Hz,

1H), 4.22 (d, J ) 2.7 Hz, 1H), 4.12-4.18 (m, 2H), 3.65-3.89

(m, 7H), 3.58 (s, 3H), 3.32-3.53 (m, 6H), 3.20 (dd, J ) 9.8, 8.8

Hz, 1H), 3.05-3.11 (m, 1H), 1.79-1.94 (m, 2H), 1.18-1.29 (m,

2H), 1.07-1.17 (m, 2H), 0.84-0.93 (m, 2H); ¹³C NMR (100

MHz, CD₃OD) δ 175.57, 169.79, 169.49, 167.24, 135.59, 134.57,

132.93, 131.11, 130.94, 129.77, 124.33, 124.12, 102.83, 99.21,

96.27, 77.43, 76.78, 76.50, 73.01, 72.46, 72.36, 72.22, 71.17,

71.10, 70.30, 69.83, 69.78, 66.04, 62.81, 62.33, 58.42, 51.96,

Sa cch a r id e 89. This compound was prepared from the

corresponding fully protected saccharide 55 (26.0 mg, 0.01573

mmol) as described in the preparation of 62, yielding 89 (5.7

mg, 48%) as a solid after lyophilization: ¹H NMR (400 MHz,

D₂O) R: â ) 1:3, for â-isomer, δ 7.71-7.78 (m, 4H), 5.10 (d, J

) 8.6 Hz, 1H), 4.33 (d, J ) 7.4 Hz, 1H), 4.31 (d, J ) 7.6 Hz,

1H), 4.19 (dd, J ) 10.7, 8.8 Hz, 1H), 4.12 (dd, J ) 11.4, 1.6

Hz, 1H), 3.35-3.86 (m, 21H), 1.67-1.75 (m, 1H), 1.53-1.61

(m, 1H), 1.14-1.27 (m, 2H), 1.03-1.10 (m, 1H), 0.89-0.97 (m,

1H), 0.70-0.82 (m, 2H); HRMS (M + Cs) calcd for C₃₃H₄₇O₁₉

-

NCs 894.1797, found 894.1771.

Ack n ow led gm en t. The financial support by Novar-

tis Pharma AG is gratefully acknowledged. X.S.Y. would

like to thank Dr. Zhiyuan Zhang for his helpful discus-

sions.

Su p p or tin g In for m a tion Ava ila ble: Listing of selected

¹H and ¹³C NMR spectra for compounds prepared. This

material is available free of charge via the Internet at

http://pubs.acs.org.

34.49, 29.76, 26.44, 25.34; HRMS (M + Cs) calcd for C₄₀H₅₁O₂₀

NCs 998.2059, found 998.2019.

-

J O991558W

Article Doi

Anomeric reactivity-based one-pot oligosaccharide synthesis: A rapid route to oligosaccharide libraries

DOI: 10.1021/jo991558w

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