Homologation of protected hexoses with Grignard C1 reagents

TETRAHEDRON

Pergamon

Tetrahedron 56 (2000) 9319±9337

Homologation of Protected Hexoses with Grignard C₁Reagents

*

Mikhail Kim, Barbara Grzeszczyk and Aleksander Zamojski

Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland

Received 30 June 2000; revised 29 August 2000; accepted 14 September 2000

AbstractÐDerivatives of three stereoisomeric hexodialdo-1,5-pyranosides were reacted with four Grignard C₁reagents: methoxymethyl-,

allyloxymethyl-, benzyloxymethyl, and dimethylphenylsilylmethyl-magnesium chlorides. Two stereoisomeric heptoses were obtained in

each case in a good yield. The methyl alloside-derived heptosides were accompanied by C-5 inverted products. The addition of Grignard

reagents to aldehydes 5±8 has been discussed in terms of parallel a- or b-chelated and Felkin±Anh transition states. It has been found that the

silyl Grignard reagent 12 exhibits a strong preference for the formation of heptose derivatives of l-con®guration at C-6. q 2000 Elsevier

Introduction

For the present study four hexodialdo-1,5-pyranoses have

been selected: methyl 2,3,4-tri-O-benzyl-b-d-allo-, -a-d-

gluco, -galacto-dialdo-1,5-pyranosides (5±7), and 1,2:3,4-

di-O-isopropylidene-a-d-galacto-dialdo-1,5-pyranose (8).

Conversion of 2,3,4-protected alkyl mannopyranoside to

the corresponding heptosides of d- and l-glycero-d-manno

con®guration according to the same protocol has been

extensively described in literature.^2±11

We recently performed a series of homologation reactions

of pentofuranoses leading to hexofuranoses.¹The reactions

consisted of elongation of all stereoisomeric, protected

pentofuranoses [pentodialdo-1,4-furanoses (1, n1)] at the

terminal C-atom (C-5) with Grignard C₁reagents (Scheme

1). The following conclusions emerged from this study: (i)

homologated products 2 and 3 were obtained in good to very

good yields as mixtures of stereoisomers at C-5; their

separation could be readily achieved by simple column

chromatography, (ii) the stereoselectivity of the reactions

depended on the possibility of forming a- or b-chelates in

the transition state, this leading to a preference of l- or

d-stereoisomers (a- or b-chelates, respectively), (iii) the

silyl Grignard reagent (12) displayed a distinct preference

for a-chelation which resulted in a dominating formation of

l- hexoses, (iv) in some cases (substrates of the ribo and

xylo con®guration) side products 4, with inverted con®gura-

tion at C-4 were obtained.

Results

Four aldehydes 5±8 (Fig. 1) were prepared by conventional

methods (cf. Experimental). The aldehydes were reacted

with four freshly prepared Grignard reagents 9±12. The

products were isolated by column chromatography. The

results of reactions are presented in Tables 1±4.

It must be stressed again¹that high yields of reactions are

secured if the reaction conditions (cf. Experimental) are

Scheme 1.

Keywords: hexopyranoses; heptopyranoses; Grignard C₁reagents; homologation reaction.

* Corresponding author. Tel.: 148-22-6323221-2120; fax: 148-22-632-6681; e-mail: awzam@icho.edu.pl

PII: S0040-4020(00)00847-4

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M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

Figure 1.

Table 1. Chain-elongation reactions of protected hexose aldehydes 5±8 with Grignard reagents 9±12. Methyl 2,3,4-tri-O-benzyl-b-d-allo-hexodialdo-1,5-

pyranoside (5)

Entry No.

Reagent

Overall yield (%)

X

Compd No. (proportions, %)

1

2

9

84.0

90.2

BnO

13 (38)

17 (31)

14 (51)

18 (55)

15 (6)

16 (5)

19 (10)

20 (4)

23 (12)

-

10

MeO

3

4

11

12

77.2

70.2

AllO

PhMe₂Si

21 (40)

±

22 (48)

24 (100)

Table 2. Chain-elongation reactions of protected hexose aldehydes 5±8 with Grignard reagents 9±12. Methyl 2,3,4-tri-O-benzyl-a-d-gluco-hexodialdo-1,5-

pyranoside (6)

Entry No.

Reagent

Overall yield (%)

X

Compd No. (proportions, %)

5

6

7

8

9

88.5

89.1

91.5

87.6

BnO

MeO

AllO

PhMe₂Si

25 (60)

26 (40)

28 (55)

30 (45)

31 (100)

10

11

12

27 (45)

29 (55)

±

Table 3. Chain-elongation reactions of protected hexose aldehydes 5±8 with Grignard reagents 9±12. Methyl 2,3,4-tri-O-benzyl-a-d-galacto-hexodialdo-1,5-

pyranoside (7)

Entry No.

Reagent

Overall yield (%)

X

Compd No. (proportions, %)

9

79.8

91.8

87.2

82.1

BnO

MeO

AllO

PhMe₂Si

32 (60)

33 (40)

35 (18)

37 (21)

39 (98)

10

11

12

10

11

12

34 (82)

36 (79)

38 (2)

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

9321

Table 4. Chain-elongation reactions of protected hexose aldehydes 5±8 with Grignard reagents 9±12. 1,2:3,4-Di-O-isopropylidene-a-d-galacto-hexodialdo-

1,5-pyranose (8)

Entry No.

Reagent

Overall yield (%)

X

Compd No. (proportions, %)

13

14

15

16

9

79.6

82.2

79.0

76.0

BnO

MeO

AllO

PhMe₂Si

40 (54)

42 (82)

44 (79)

46 (52)

41 (46)

43 (18)

45 (21)

47 (48)

10

11

12

strictly observed. The formation of Grignard reagents 9±11

is strongly dependent on the quality of the chloromethyl

ethers used. We have constantly used freshly prepared and

freshly distilled alkyl chloromethyl ethers. Grignard

reagents prepared are rather unstable and should be

kept below 2208C. Silyl reagent 12 is stable and the

reactions can be performed under typical conditions. The

overall yields of products were high. The products were

separated by column chromatography, in some cases as

6-O-benzoates (cf. Experimental). Assignment of con®gura-

tion to all stereoisomers is discussed in a separate section

below.

contain an a-oxygen atom (pyranose ring oxygen) and

also a b-oxygen atom in a sterically de®ned position:

trans (5 and 6) or cis (7 and 8) in relation to the carbonyl

group. It is known that these atoms may in¯uence the steric

course of addition of nucleophiles due to the chance of

forming a- or b-chelates.¹³

The question of a- and b-chelation in a- and b-alkoxy-

aldehydes and -ketones during nucleophilic additions has

been studied experimentally^14±19and theoretically.^20,21

Most relevant experimental investigations have been

performed by E. L. Eliel^19,22,23and theoretical calculations

by E. Nakamura and K. Morokuma.²⁴From the experiments

it is known that a-chelation has a distinct in¯uence on the

As it can be seen from the Tables 1±4, there is a similarity in

the stereochemical outcome of reactions for all reagents of

the ROCH₂MgCl type. The stereochemical results for

Grignard 12 are different.

In the case of the galacto aldehydes (7 and 8) products of the

d-glycero con®guration (position C-6) dominated over the

l-glycero partners (from 1.5:1 to 4:1, Tables 3 and 4). The

allo aldehyde 5 yielded products where l-glycero stereo-

isomers slightly prevailed (1.3:1) over the d-glycero

isomers (Table 1). The gluco aldehyde 6 led to both stereo-

isomeric heptosides with a slight prevalence of the

d-glycero isomer (Table 2). The so-called `inverted'

products, i.e. methyl heptosides stemming from the

aldehyde with inverted con®guration at C-5, were obtained

only in the case of methyl alloside elongated with alkoxy-

methyl Grignards 9±11. Their yield remained within

10±14%. Although in two cases (Table 1, entries 1 and 2)

the stereoisomeric products 15, 16 and 19, 20 could be

obtained as individuals, their con®guration at C-6 was not

determined.

Figure 2. (a) a-chelation, (b) b-chelation.

Discussion

Chain elongation of hexoses is of preparative value as the

reactions may afford heptoses of any desired con®guration.

Several heptoses occur in nature, often as components of

polysaccharides.¹²Synthetic access to these sugars using

this homologation method may often be regarded as the

`method of choice'.

From the stereochemical point of view, the reactions present

a contribution to the well-known problem of nucleophilic

additions to a-oxyaldehydes. All four aldehydes 5±8

Figure 3. Methyl 2,3,4-tri-O-benzyl-7-O-methyl-l-glycero-b-d-allo-

heptopyranoside (18).

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M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

Scheme 2. (i) C₆H₅CH₂Br, NaH, DMF, (ii) 1. Rh(PPh₃)₃Cl, DABCO, EtOH/benzene/H₂O (9:2:1), 2. HgO, HgCl₂, (iii) Mel, NaH, DMF, (iv) CH₃CO₃H, KBr,

CH₃CO₂H, CH₃CO₂Na.

stereochemical result of reactions.¹⁹According to Eliel,

b-chelation appears less important in steering the approach

of nucleophiles to the carbonyl group.^19,25However, ab

initio calculations indicate that both types of chelation

facilitate product formation through low-energy transition

states (TS).²⁴

the `normal' FA pathway is equally important as the

a-chelation.

The `inverted' products from the reactions of the allo

aldehyde 5 were formed most probably¹by epimerization

of the aldehyde caused by the excessive Grignard reagent

before reacting with it. Although this seems to be the most

rational explanation, it must be added that our isomerization

experiments with some isopropylidene-protected pento-

dialdo-1,4-furanosides with a strong base (lithium diiso-

propylamide) did not afford a conclusive evidence.²⁶

From our results, discussed earlier,¹and presented in this

work, both types of chelation play an important role in

determining the stereochemical outcome of reactions. At

the same time we cannot exclude the participation of a

non-chelated reaction pathway. Thus, the low stereo-

selectivity of addition of alkoxymethyl Grignards 9±11 to

allo and gluco aldehydes (5 and 6, Tables 1 and 2) with only

a slight preference for the l-glycero stereoisomers can be

explained by an interplay of two reaction pathways: by the

`normal' Felkin±Anh (FA) transition state, competing

with an a-chelated TS. It should be added that in this case

a-chelation forces the approach of the nucleophile from

`below the ring' (Fig. 2a) this leading to l-con®guration

of the new CHOH grouping. Products of the d-con®guration

at C-6 are formed via the non-chelated FA TS. In the case of

both galacto aldehydes, 7 and 8, the FA transition state is

additionally supported by b-chelation (Fig. 2b) this giving a

clear preference of the d-glycero stereoisomers (Tables 3

and 4).

Con®guration of d- and l-glycero-d-allo-, gluco- and

-galacto-heptopyranosides

Derivatives of the heptopyranosides obtained were, with a

few exceptions, not described in literature, therefore their

The stereochemical outcome of the reactions between

hexose aldehydes 5 and 6 and the silyl Grignard is unidirec-

tional: only products of l-glycero con®guration were

isolated. The alternative stereoisomersÐif formedÐwere

in negligible amounts (,1%). In the case of the aldehyde

7 the d-glycero stereoisomer 38 was obtained in 1.3%

isolated yield, and in the case of the aldehyde 8 both C-6

stereoisomeric products were formed in approximately

equal amounts. The rationalization is based in the assump-

tion that for the silyl Grignard the a-chelation plays the

decisive role. However, it appears that for the aldehyde 8

Figure 4. Methyl 2,3,4-tri-O-benzyl-7-O-methyl-l-glycero-a-d-gluco-

heptopyranoside (28).

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

9323

Scheme 3.

Scheme 4.

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M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

Scheme 5.

identi®cation was based on conversion to products con-

®guration of which was determined by X-ray method.

pyranosides (13 and 14) were fully deprotected to free

heptoses by acetolysis followed by hydrogenolysis to

yield free sugars 53 and 54. The optical rotation and ¹³C

NMR data of d-glycero-a,b-d-allo-heptopyranose (53)

were identical with the literature values.^27,28

From methyl 2,3,4,-tri-O-benzyl-7-O-methyl-l-glycero-b-

d-allo-heptopyranoside (18, Table 1) crystals suitable for

X-ray structural determination were obtained, what enabled

to assign l con®guration at C-6 (Fig. 3) The corelation of the

spectral data of 18 with other products obtained: 14 (7-O-

benzyl), 22 (7-O-allyl) and 24 [7-deoxy-7-(dimethylphenyl-

silyl)] is shown in Scheme 2. Heptoside 22 was benzylated

at C-6 and the product 49 was de-allylated under typical

conditions (Wilkinson's catalyst, DABCO, then hydrolysis)

to yield 50 which was next methylated to yield 7-O-methyl

derivative identical (TLC, NMR) with 18. 7-O-Benzyl

derivative 14 was benzylated at C-6 to yield pentabenzyl

derivative 52. Parallelly, 22 was de-allylated to 6,7-diol 51.

Oxidation of 7-deoxy-7-dimethylphenylsilyl derivative 24

led to the same diol 51. And, ®nally, di-benzylation of the

diol 51 furnished pentabenzyl heptoside identical in every

respect with 52 (Scheme 2).

For the stereoisomeric methyl (dd- and ld-) gluco hepto-

pyranosides the key compound, for which an X-ray struc-

tural determination was performed, was methyl 2,3,4-tri-O-

benzyl-7-O-methyl-l-glycero-a-d-gluco-heptopyranoside

(28, Fig. 4), leaving for 27 the d-glycero-d-gluco con®gura-

tion. These assignments were further supported by com-

parison of the spectral and optical rotation data of 6,7-

diols 59 and 61 with the literature values.^29,30Structural

correlation of other products: 26, 29, 30, and 31 is shown

in Scheme 3.

Con®guration of derivatives of methyl galactoheptosides

(Table 3) was determined by corelation with methyl d-

and l-glycero-d-galacto-heptopyranosides 67 and 68.⁷All

reactions and products which were performed are collected

in Scheme 4. A basically similar structural correlation was

Both substituted methyl d- and l-glycero-b-d-allo-hepto-

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

9325

made for derivatives of diisopropylidene-d-galactose

(Scheme 5). Compounds 46, 47 (cf. Table 4) and 72 are

known from literature.³¹

DMF (130 ml) was added sodium hydride (50% suspension

in mineral oil, 3.64 g, 0.076 mol). The suspension was stir-

red for 30 min and benzyl bromide (9.0 ml, 0.076 mol) was

added. Stirring was continued for 8 h whereupon the excess

of the hydride was decomposed with MeOH and the mixture

was poured into ice-water. The product was extracted with

ether, and the organic extract was dried and concentrated to

dryness. The residue was dissolved in a mixture of CH₃CN

(80 ml) and ether (58 ml) and HBF₄(50% in water, 5.8 ml)

was added. After 2 h the solution was neutralized with Et₃N

and washed twice with water. The organic layer was dried

and evaporated to dryness under reduced pressure. The

residue was chromatographed with hexane±ethyl acetate

(10:1!3:2) to yield methyl 2,3,4-tri-O-benzyl-b-d-allo-

pyranoside (6.74 g, 63.1%) as a colourless oil; [a]_D

117.0 (c 3.0, CHCl₃); n_max(®lm) 3480 (br), 3063, 3030,

2890, 1497, 1454, 1206, 1127, 1091, 1045, 1028, 736,

Conclusion

Homologation reactions of hexodialdo-1,5-pyranoses 5±8

with C₁Grignard reagents 9±12 opens a facile access to

higher sugars. Heptoses which are otherwise dif®cult to

obtain may be prepared readily. A several 7-O etheri®ed

heptoses become available. The reactions performed present

a contribution to the problem of nucleophilic additions to

aldehydes having a- and b-oxygen atoms in sterically

de®ned positions. These results con®rm our earlier observa-

tions¹that the reactions proceed through formation of a- and

b-chelates depending on the steric accessibility of oxygen

atoms. It seems again that b-chelation to acetonide oxygen

atoms (aldehyde 9) is almost as effective as to ether oxygen

atom (aldehyde 8). It is remarkable that the silyl Grignard 12

exhibits a distinct preference for a-chelated forms in the

transition state, this leading to l-con®guration at the new

CHOH grouping.

698 cm²^{1 1}H NMR (200 MHz, CDCl₃) d: 7.46±7.22

;

(15H, m, 3Ph), 4.94±4.38 (3£2H, 3ABq, 3CH₂Ph), 4.85

(1H, d, J8.0 Hz, H-1), 4.12 (1H, dd, J2.4, 2.6 Hz,

H-3), 3.96 (1H, ddd, J3.0, 4.1, 9.5 Hz, H-5), 3.88 (1H,

dd, J3.0, 11.9 Hz, H-6a), 3.73 (1H, dd, J4.1, 11.9 Hz,

H-6b), 3.56 (3H, s, OCH₃), 3.42 (1H, dd, J2.4, 9.5 Hz,

H-4), 3.19 (1H, dd, J2.6, 8.0 Hz, H-2). ¹³C NMR

(200 MHz, CDCl₃) d: 138.8, 138.5, 137.6 and 128.4±

127.4 (Ph), 102.0 (C-1), 79.0, 75.6, 74.5 and 72.4

(C-2,3,4,5), 74.4, 72.9 and 71.5 (3CH₂Ph), 62.3 (C-6),

57.1 (OCH₃). HR MS (LSIMS): C₂₈H₃₂O₆1Na¹

[M1Na]¹; Calcd: 487.20966. Found: 487.21035.

Experimental

General methods

Melting points were determined with a Ko¯er apparatus and

are uncorrected. H NMR spectra were recorded with a

1

Methyl 2,3,4-tri-O-benzyl-b-d-allo-hexodialdo-1,5-pyra-

nose (5). A solution of oxalyl chloride (1.56 ml, 18.1 mmol)

in CH₂Cl₂(44 ml) was cooled (250 to 2608C) and a solu-

tion of Me₂SO (2.57 ml, 36.3 mmol) in CH₂Cl₂(36 ml) was

slowly added. After 5 min a solution of methyl 2,3,4-tri-O-

benzyl-b-d-allopyranoside (6.74 g, 14.5 mmol) in CH₂Cl₂

(36 ml) was slowly added. Stirring at 2608C was continued

for 1 h whereupon Et₃N (10.11 ml, 72.5 mmol) was added.

After 5 min of stirring the reaction mixture was allowed to

attain room temperature. To the solution was added water

(45 ml), and the mixture was extracted with CH₂Cl₂. The

organic extract was dried and concentrated. The residue was

puri®ed by chromatography with hexane±ethyl acetate

(10:1!2:1) to give methyl 2,3,4-tri-O-benzyl-b-d-allo-

hexodialdo-1,5-pyranose (5, 5.71 g, 85.3%) as a colourless

Varian AC-200 (200 MHz) or Bruker AM-500 (500 MHz)

spectrometers. ¹³C NMR were recorded in the DEPT mode.

The assignments of signals for compounds 13±47 was based

1

on H-¹³C COSY and H±¹H COSY spectra. Mass spectra

were recorded on an AMD-604 mass spectrometer (LSIMS,

positive mode) and on an Per Septive Biosystems Marinere

mass spectrometer (ESI/TOF, positive mode). Optical rota-

tions were determined at 22^28C with a Jasco DIP 360

automatic polarimeter and are given in 10²¹deg cm²g²¹

.

TLC was performed on Kieselgel 60 F₂₅₄ready plates and

column chromatography on Silica Gel 230±400 or 70±230

mesh (Merck). High-performance liquid chromatography

was carried out on a Shimadzu instrument: central unit

C-R4A, pump unit LC-8A, UV detector SPD250-6A on a

column SP250/21 Nucleosil 100-7 (Macherey-Nagel).

1

oil; H NMR (200 MHz, CDCl₃) d: 9.70s, 1H, (CHO),

7.48±7.20 (15H, m, 3Ph), 4.92±4.36 (8H, m, H-1, H-5,

3CH₂Ph), 4.09 (1H, t, J2.6 Hz, H-3), 3.60±3.53 (1H, m,

H-4), 3.56 (3H, s, OCH₃), 3.25 (1H, dd, J2.6, 7.5 Hz, H-2).

¹³C NMR (50 MHz, CDCl₃) d: 198.9 (CHO), 138.5, 138.4,

137.0 and 128.5±127.5 (Ph), 78.0, 76.1, 75.5, 74.4

(C-2,3,4,5), 74.3, 73.1, 71.7 (3CH₂Ph), 57.2 (OCH₃).

Aldehydes 6, 7 and 8 were obtained from readily available

methyl 2,3,4-tri-O-benzyl-a-d-gluco-,³²and -a-d-galacto-

pyranosides³³and 1,2:3,4-di-O-isopropylidene-a-d-galacto-

pyranose,³⁴respectively, by Swern oxidation. Methyl b-d-

allopyranoside was obtained from the commercially

available methyl b-d-gluco-pyranoside by Mitsunobu

reaction in according to Weinges.^35,36

The synthesis of protected derivatives of

heptopyranosides

Methyl 2,3,4-tri-O-benzyl-b-d-allopyranoside. To

a

suspension of methyl b-d-allopyranoside (4.47 g, 0.023

mol) in pyridine (80 ml) was added trityl chloride (7.80 g,

0.028 mol) and a catalytic amount of DMAP. The mixture

was stirred overnight at 408C. Then water (190 ml) was

added and after 10 min the product was extracted with

chloroform. The organic extract was dried and concentrated

to dryness. To a cooled (08C) solution of the residue in abs

General method. To dry magnesium turnings (474 mg,

19.5 mmol) covered with freshly distilled THF (1 ml)

under dry argon was added sublimed HgCl₂(18 mg), and

a few drops of neat, freshly distilled alkoxymethyl chloride

were added while lowering the temperature to 2158C (for

allyloxymethyl chloride), 0 to 258C (for benzyloxymethyl

chloride) or 2208C (for methyloxymethyl chloride). When

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M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

the formation of the Grignard reagent had started, the rest of

the alkoxymethyl chloride (19.5 mmol) in THF (2 ml) was

added at 2208C (for allyloxymethyl chloride), 2108C (for

benzyloxymethyl chloride) or 2258C (for methoxymethyl

chloride) and the stirring was continued for 2 h. The

temperature was then lowered to 2788C and a solution of

aldehyde (3.25 mmol) in abs THF (8 ml) was added drop-

wise. The mixture was stirred at this temperature for 2 h and

was slowly brought to room temperature while stirring for

another 12 h. Cold (08C) aq NH₄Cl (82 ml) was added and

the products were extracted with CH₂Cl₂. The extract was

dried with MgSO₄and concentrated, and the residue was

chromatographed on a silica gel column. In case of dif®cult

separable products HPLC was used.

1053, 736, 698 cm²¹; ¹H NMR (500 MHz, CDCl₃) d: 7.39±

7.21 (20H, m, 4Ph), 5.07±4.40 (4£2H, 4ABq, 4CH₂Ph),

4.97 (1H, d, J1.3 Hz, H-1), 4.16±4.13 (1H, m, H-6),

3.88±3.86 (1H, m, H-4), 3.83 (1H, dd, J1.5, 4.9 Hz, H-

5), 3.78±3.75 (1H, m, H-2), 3.74 (1H, dd, J2.9, 3.1 Hz, H-

3), 3.57 (1H, dd, J5.7, 9.8 Hz, H-7a), 3.39 (1H, dd, J4.6,

9.8 Hz, H-7b), 3.32 (3H, s, OCH₃). ¹³C NMR (125 MHz,

CDCl₃) d: 138.5, 138.5, 138.1, 138.0 and 128.4±127.2 (Ph),

100.3 (C-1), 77.6 (C-3), 74.8 (C-4), 74.2 (C-2), 73.4

(CH₂Ph), 73.4 (CH₂Ph), 73.1 (CH₂Ph), 71.2 (CH₂Ph), 70.9

(C-6), 70.1 (C-5), 69.7 (C-7), 54.9 (OCH₃). HR MS (ESI):

C₃₆H₄₀O₇1Na¹[M1Na]¹; Calcd: 607.2666. Found:

607.2645.

Methyl 2,3,4,7-tetra-O-benzyl-d(l)-glycero-a-l-talo-hepto-

pyranoside (16). HPLC eluent: CH₂Cl₂±ether 8:1; yield

5%; colourless oil; [a]_D232.6 (c 2.1, CHCl₃); n_max

(®lm) 3480 (br), 3031, 2908, 1497, 1454, 1360, 1205,

Grignard reagent 12, containing phenyldimethylsilyl group,

was obtained according to Boons et al.³⁷The reactions of 12

with hexodialdo-1,5-pyranoses (5±8) were performed in the

same manner at 2788C.

1134, 1055, 973, 910, 736, 698 cm²¹

;

¹H NMR

(500 MHz, C₆D₆) d: 7.53±7.06 (20H, m, 4Ph), 5.26±4.26

(4£2H, 4ABq, 4CH₂Ph), 4.86 (1H, d, J1.1 Hz, H-1), 4.44

(1H, ddd, J3.1, 4.9, 8.9 Hz, H-6), 4.24±4.22 (1H, m, H-4),

3.83±3.81 (1H, m, H-2), 3.80 (1H, dd, J1.4, 8.9 Hz, H-5),

3.77 (1H, dd, J3.1, 3.2 Hz, H-3), 3.72 (1H, dd, J4.9,

9.5 Hz, H-7a), 3.65 (1H, dd, J3.1, 9.5 Hz, H-7b), 3.07

(3H, s, OCH₃). ¹³C NMR (125 MHz, C₆D₆) d: 140.3,

139.6, 139.1, 138.7 and 128.6±127.2 (Ph), 100.8 (C-1),

77.9 (C-3), 75.4 (C-2), 74.6 (CH₂Ph), 73.5 (CH₂Ph), 73.5

(C-4), 73.3 (CH₂Ph), 71.8 (C-7), 71.2 (C-5), 70.9 (CH₂Ph),

68.7 (C-6), 54.4 (OCH₃). HR MS (ESI): C₃₆H₄₀O₇1Na¹

[M1Na]¹; Calcd: 607.2666. Found: 607.2662.

Methyl 2,3,4,7-tetra-O-benzyl-d-glycero-b-d-allo-hepto-

pyranoside (13). HPLC eluent: CH₂Cl₂±ether 8:1; yield:

33%; colourless needles, mp 72±738C (from hexane±

ether); [a]_D112.7 (c 1.4, CHCl₃); n_max(KBr) 3402 (br),

3031, 2881, 1497, 1454, 1209, 1134, 1091, 1060, 1026, 735,

697 cm²¹; ¹H NMR (500 MHz, CDCl₃) d: 7.39±7.20 (20H,

m, 4Ph), 4.90±4.30 (4£2H, 4ABq, 4CH₂Ph), 4.78 (1H, d,

J7.9 Hz, H-1), 4.10 (1H, dd, J2.4, 2.6 Hz, H-3), 4.08±

4.01 (2H, m, H-5, H-6), 3.60 (1H, dd, J6.1, 10.0 Hz,

H-7a), 3.58 (1H, dd, J3.7, 10.0 Hz, H-7b), 3.47 (1H, dd,

J2.4, 9.2 Hz, H-4), 3.47 (3H, s, OCH₃), 3.17 (1H, dd,

J2.6, 7.9 Hz, H-2). ¹³C NMR (125 MHz, CDCl₃) d:

138.8, 138.6, 138.3, 137.1 and 128.5±127.4 (Ph), 102.1

(C-1), 78.9 (C-2), 77.9 (C-4), 74.4 (CH₂Ph), 74.1 (C-3),

73.3 (CH₂Ph), 72.9 (CH₂Ph), 72.4 (C-6), 71.6 (C-5), 71.0

(CH₂Ph), 70.9 (C-7), 56.8 (OCH₃). HR MS (ESI):

C₃₆H₄₀O₇1Na¹[M1Na]¹; Calcd: 607.2666. Found:

607.2663. Anal. Calcd for C₃₆H₄₀O₇: C, 73.95; H, 6.90.

Found: C, 74.08; H, 7.04.

Methyl 2,3,4-tri-O-benzyl-7-O-methyl-d-glycero-b-d-allo-

heptopyranoside (17). HPLC eluent: hexane±ethyl acetate

3:2; yield 28%; colourless needles, mp 92±938C (from

hexane±ethyl acetate); [a]_D125.2 (c 1.1, CHCl₃); n_max

(KBr) 3401 (br), 3031, 2922, 2813, 1496, 1455, 1201,

1

1134, 1092, 1027, 745, 696 cm²¹; H NMR (500 MHz,

CDCl₃) d: 7.40±7.24 (15H, m, 3Ph), 4.91±4.34 (3£2H,

3ABq, 3CH₂Ph), 4.80 (1H, d, J8.0 Hz, H-1), 4.12 (1H,

dd, J2.4, 2.6 Hz, H-3), 4.02±3.97 (2H, m, H-5, H-6),

3.52 (3H, s, OCH₃), 3.53±3.44 (3H, m, H-4, H-7a, H-7b),

Methyl 2,3,4,7-tetra-O-benzyl-l-glycero-b-d-allo-hepto-

pyranoside (14). HPLC eluent: CH₂Cl₂±ether 8:1; yield

43%; colourless oil; [a]_D28.7 (c 1.2, CHCl₃); n_max

(®lm) 3478 (br), 3063, 3030, 2901, 1497, 1454, 1362,

3.34 (3H, s, OCH₃), 3.18 (1H, dd, J2.6, 8.0 Hz, H-2). ¹³

C

NMR (125 MHz, CDCl₃) d: 138.8, 138.6, 137.0 and 128.5±

127.4 (Ph), 102.1 (C-1), 78.9 (C-2), 78.1 (C-4), 74.5

(CH₂Ph), 74.1 (C-3), 73.2 (C-7), 73.0 (CH₂Ph), 72.3, 71.5

(C-5, C-6), 70.9 (CH₂Ph), 59.1 (OCH₃), 56.8 (OCH₃). Anal.

Calcd for C₃₀H₃₆O₇: C, 70.85; H, 7.13. Found: C, 70.66; H,

7.13.

;

1206, 1096, 1048, 1028, 737, 698 cm²^{1 1}H NMR

(500 MHz, CDCl₃) d: 7.40±7.24 (20H, m, 4Ph), 4.87±

4.51 (4£2H, 4ABq, 4CH₂Ph), 4.77 (1H, d, J7.9 Hz,

H-1), 4.14 (1H, ddd, J1.4, 5.2, 7.7 Hz, H-6), 4.08 (1H,

dd, J2.2, 2.6 Hz, H-3), 3.93 (1H, dd, J1.4, 9.7 Hz,

H-5), 3.65 (1H, dd, J7.7, 9.7 Hz, H-7a), 3.59 (1H, dd,

J2.2, 9.7 Hz, H-4), 3.59 (1H, dd, J5.2, 9.7 Hz, H-7b),

Methyl 2,3,4-tri-O-benzyl-7-O-methyl-l-glycero-b-d-allo-

heptopyranoside (18). HPLC eluent: hexane±ethyl acetate

3:2; yield 50%; colourless needles, mp 69±708C (from

hexane±ether); [a]_D210.5 (c 1.0, CHCl₃); n_max(KBr)

3421 (br), 3030, 2892, 1497, 1454, 1208, 1136, 1098,

3.44 (3H, s, OCH₃), 3.17 (1H, dd, J2.6, 7.9 Hz, H-2). ¹³

C

NMR (125 MHz, CDCl₃) d: 139.0, 138.6, 138.1, 137.9 and

128.4±127.3 (Ph), 102.0 (C-1), 78.8 (C-2), 75.3 (C-4), 75.0

(C-3), 74.4 (CH₂Ph), 73.3 (CH₂Ph), 72.8 (CH₂Ph), 71.9

(CH₂Ph), 71.7 (C-7), 71.7 (C-5), 68.2 (C-6), 56.7 (OCH₃).

HR MS (ESI): C₃₆H₄₀O₇1Na¹[M1Na]¹; Calcd: 607.2666.

Found: 607.2696.

1046, 1026, 970, 737, 697 cm²^{1 1}H NMR (500 MHz,

;

CDCl₃) d: 7.41±7.24 (15H, m, 3Ph), 4.87±4.51 (3£2H,

3ABq, 3CH₂Ph), 4.80 (1H, d, J7.9 Hz, H-1), 4.12±4.08

(1H, m, H-6), 4.10 (1H, dd, J2.5, 2.6 Hz, H-3), 3.90 (1H,

dd, J1.4, 9.7 Hz, H-5), 3.59 (1H, dd, J2.5, 9.7 Hz, H-4),

3.57 (1H, dd, J7.9, 9.8 Hz, H-7a), 3.51 (3H, s, OCH₃),

3.49 (1H, dd, J4.7, 9.8 Hz, H-7b), 3.38 (3H, s, OCH₃),

3.18 (1H, dd, J2.6, 7.9 Hz, H-2). ¹³C NMR (125 MHz,

Methyl 2,3,4,7-tetra-O-benzyl-d(l)-glycero-a-l-talo-hepto-

pyranoside (15). HPLC eluent: CH₂Cl₂±ether 8:1; yield

4%; colourless oil; [a]_D26.4 (c 1.1, CHCl₃); n_max(®lm)

3481 (br), 3064, 3031, 2907, 1497, 1454, 1359, 1206, 1131,

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

9327

CDCl₃) d: 139.0, 138.6, 137.9 and 128.4±127.4 (Ph), 102.0

(C-1), 78.8 (C-2), 75.2 (C-4), 75.0 (C-3), 74.5 (CH₂Ph), 74.4

(C-7), 72.8 (CH₂Ph), 71.9 (CH₂Ph), 71.8 (C-5), 68.0 (C-6),

59.1 (OCH₃), 56.8 (OCH₃). Anal. Calcd for C₃₀H₃₆O₇: C,

70.85; H, 7.13. Found: C, 70.64; H, 7.07.

(Ph), 117.0 (OCH₂CHCH₂), 102.1 (C-1), 78.9 (C-2), 78.0

(C-4), 74.4 (CH₂Ph), 74.1 (C-3), 73.0 (CH₂Ph), 72.5 and

71.6 (C-5, C-6), 72.3 (OCH₂CHCH₂), 71.0 (CH₂Ph), 70.8

(C-7), 56.8 (OCH₃). Anal. Calcd for C₃₂H₃₈O₇: C, 71.89; H,

7.16. Found: C, 71.88; H, 7.33.

Methyl 2,3,4-tri-O-benzyl-7-O-methyl-d(l)-glycero-a-l-

talo-heptopyranoside (19). HPLC eluent: hexane±ethyl

acetate 3:2; yield 4%; colourless oil; [a]_D29.7 (c 1.0,

CHCl₃); n_max(®lm) 3479 (br), 3064, 3031, 2902, 1497,

1454, 1360, 1200, 1129, 1053, 1029, 969, 766, 736,

698 cm²¹;¹H NMR (500 MHz, CDCl₃) d: 7.39±7.21

(15H, m, 3Ph), 5.13±4.50 (3£2H, 3ABq, 3CH₂Ph), 4.98

(1H, d, J1.2 Hz, H-1), 4.14±4.09 (1H, m, H-6), 3.94±

3.91 (1H, m, H-4), 3.80±3.75 (3H, m, H-2, H-3, H-5),

3.44 (1H, dd, J5.5, 9.8 Hz, H-7a), 3.34 (3H, s, OCH₃),

3.30 (3H, s, OCH₃), 3.29 (1H, dd, J5.0, 9.8 Hz, H-7b).

¹³C NMR (125 MHz, CDCl₃) d: 138.5, 138.4, 138.1 and

128.4±127.2 (Ph), 100.3 (C-1), 77.6 (C-3), 74.8 (C-4),

74.1 and 70.1 (C-2, 5), 73.4 (CH₂Ph), 73.1 (CH₂Ph), 72.3

(C-7), 71.3 (CH₂Ph), 70.7 (C-6), 59.1 (OCH₃), 54.9 (OCH₃).

¹H NMR (500 MHz, C₆D₆) d: 7.37±7.03 (15H, m, 3Ph),

5.16±4.25 (3£2H, 3ABq, 3CH₂Ph), 4.98 (1H, d,

J1.7 Hz, H-1), 4.32±4.28 (1H, m, H-6), 3.99 (1H, dd,

J2.1, 3.7 Hz, H-5), 3.85±3.82 (1H, m, H-4), 3.74 (1H,

dd, J1.7, 3.3 Hz, H-2), 3.71 (1H, dd, J3.0, 3.2 Hz,

H-3), 3.69 (1H, dd, J6.9, 9.6 Hz, H-7a), 3.54 (1H, dd,

J4.6, 9.6 Hz, H-7b), 3.15, 3.12 (2£3H, 2s, 2OCH₃). HR

MS (ESI): C₃₀H₃₆O₇1H¹[M1H]¹; Calcd: 509.2534.

Found: 509.2553.

Methyl 7-O-allyl-2,3,4-tri-O-benzyl-l-glycero-b-d-allo-

heptopyranoside (22). HPLC eluent: CH₂Cl₂±ether 8:1;

yield 37%; colourless oil; [a]_D29.2 (c 1.4, CHCl₃);

n_max(®lm) 3480 (br), 3064, 3030, 2902, 1497, 1454,

1

1206, 1095, 1048, 1028, 926, 737, 698 cm²¹; H NMR

(500 MHz, CDCl₃) d: 7.45±7.22 (15H, m, 3Ph), 5.95±

5.86 (1H, m, OCH₂CHvCH₂), 5.30±5.15 (2H, m,

OCH₂CHvCH₂), 4.88±4.49 (3£2H, 3ABq, 3CH₂Ph), 4.79

(1H, d, J7.9 Hz, H-1) 4.13±4.08 (1H, m, H-6), 4.09 (1H,

dd, J2.5, 2.6 Hz, H-3), 4.07±3.97 (2H, m,

OCH₂CHvCH₂), 3.92 (1H, dd, J1.4, 9.7 Hz, H-5), 3.62

(1H, dd, J7.7, 9.8 Hz, H-7a), 3.60 (1H, dd, J2.5, 9.7 Hz,

H-4), 3.56 (1H, dd, J4.8, 9.8 Hz, H-7b), 3.50 (3H, s,

OCH₃), 3.18 (1H, dd, J2.6, 7.9 Hz, H-2). ¹³C NMR

(125 MHz, CDCl₃) d: 139.0, 138.6 and 137.9 (Ph), 134.7

(OCH₂CHvCH₂),

128.4±127.3

(Ph),

117.1

(OCH₂CHvCH₂), 102.0 (C-1), 78.8 (C-2), 75.3 (C-4),

75.1 (C-3), 74.5 (CH₂Ph), 72.8 (CH₂Ph), 72.3

(OCH₂CHvCH₂), 71.9 (CH₂Ph), 71.8 (C-7), 71.7 (C-5),

68.2 (C-6), 56.7 (OCH₃). HR MS (ESI): C₃₂H₃₈O₇1Na¹

[M1Na]¹; Calcd: 557.2510. Found: 557.2499.

Methyl 7-O-allyl-2,3,4-tri-O-benzyl-d(l)-glycero-a-l-

talo-heptopyranoside (23). HPLC eluent: CH₂Cl₂±ether

8:1; yield 9%; colourless oil; [a]_D243.5 (c 1.8, CHCl₃);

Methyl 2,3,4-tri-O-benzyl-7-O-methyl-l(d)-glycero-a-l-

talo-heptopyranoside (20). HPLC eluent: hexane±ethyl

acetate 3:2; yield 9%; colourless oil; [a]_D246.2 (c 2.1,

CHCl₃); n_max(®lm) 3471 (br), 3031, 2907, 1497, 1454,

n_max(®lm) 3471 (br), 3064, 3031, 2910, 2867, 1497, 1454,

1359, 1202, 1135, 1055, 1028, 736, 698 cm²¹; H NMR

(500 MHz, CDCl₃) d: 7.42±7.20 (15H, m, 3Ph), 5.92±

5.84 (1H, m, OCH₂CHvCH₂), 5.27±5.14 (2H, m,

OCH₂CHvCH₂), 5.06±4.50 (3£2H, 3ABq, 3CH₂Ph), 4.83

(1H, d, J1.1 Hz, H-1), 4.22 (1H, ddd, J3.5, 4.7, 9.0 Hz,

H-6), 4.15±4.12 (1H, m, H-4), 4.03±3.95 (2H, m,

OCH₂CHvCH₂), 3.76 (1H, dd, J1.1, 3.3 Hz, H-2), 3.71

(1H, dd, J3.1, 3.3 Hz, H-3), 3.66 (1H, dd, J1.3, 9.0 Hz,

H-5), 3.65 (1H, dd, J3.5, 9.8 Hz, H-7a), 3.62 (1H, dd,

J4.7, 9.8 Hz, H-7b), 3.28 (3H, s, OCH₃). ¹³C NMR

(125 MHz, CDCl₃) d: 139.2, 138.7 and 138.3 (Ph), 134.5

1

1360, 1198, 1134, 1055, 953, 907, 736, 698 cm²^{1 1}H

;

NMR (500 MHz, C₆D₆) d: 7.53±7.06 (15H, m, 3Ph),

5.27±4.32 (3£2H, 3ABq, 3CH₂Ph), 4.87 (1H, d,

J1.1 Hz, H-1), 4.40±4.36 (1H, m, H-6), 4.26±4.23 (1H,

m, H-4), 3.83 (1H, dd, J1.1, 3.4 Hz, H-2), 3.78 (1H, dd,

J3.1, 3.4 Hz, H-3), 3.76 (1H, dd, J1.4, 8.9 Hz, H-5), 3.58

(1H, dd, J4.9, 9.5 Hz, H-7a), 3.48 (1H, dd, J3.0, 9.5 Hz,

H-7b), 3.10, 3.04 (2£3H, 2s, 2OCH₃). ¹³C NMR (125 MHz,

C₆D₆) d: 140.1, 139.4, 138.8 and 128.3±126.9 (Ph), 100.6

(C-1), 77.7 (C-3), 75.1 (C-2), 74.4 (CH₂Ph), 73.6 (C-7), 73.2

(C-4), 73.0 (CH₂Ph), 70.9 (C-5), 70.6 (CH₂Ph), 68.3 (C-6),

58.3 and 54.1 (2OCH₃). HR MS (LSIMS): C₃₀H₃₆O₇1Na¹

[M1Na]¹; Calcd: 531.23587. Found: 531.23506.

(OCH₂CHvCH₂),

128.3±127.1

(Ph),

117.1

(OCH₂CHvCH₂), 100.6 (C-1), 77.4 (C-3), 74.0 (CH₂Ph),

74.0 (C-2), 73.2 (CH₂Ph), 72.3 (C-4), 72.2

(OCH₂CHvCH₂), 70.9 (C-7), 70.8 (CH₂Ph), 70.4 (C-5),

68.0 (C-6), 54.7 (OCH₃). HR MS (ESI): C₃₆H₄₀O₇1H¹

[M1H]¹; Calcd: 535.2690. Found: 535.2672. Anal. Calcd

for C₃₂H₃₈O₇: C, 71.89; H, 7.16. Found: C, 71.68; H, 7.02.

Methyl 7-O-allyl-2,3,4-tri-O-benzyl-d-glycero-b-d-allo-

heptopyranoside (21). HPLC eluent: CH₂Cl₂±ether 8:1;

yield: 31%; colourless needles, mp 80±818C (from hexane±

ether); [a]_D121.9 (c 1.1, CHCl₃); n_max(KBr) 3410 (br),

3033, 2921, 1497, 1455, 1204, 1134, 1067, 1025, 923, 739,

696 cm²¹; ¹H NMR (500 MHz, CDCl₃) d: 7.40±7.22 (15H,

m, 3Ph), 5.93±5.84 (1H, m, OCH₂CHCH₂), 5.26±5.12 (2H,

m, OCH₂CHCH₂), 4.91±4.34 (3£2H, 3ABq, 3CH₂Ph), 4.80

(1H, d, J7.9 Hz, H-1), 4.12 (1H, dd, J2.4, 2.6 Hz, H-3),

4.05±4.00 (2H, m, H-5, H-6), 4.00±3.94 (2H, m,

OCH₂CHCH₂), 3.58±3.51 (2H, m, H-7a, H-7b), 3.52 (3H,

s, OCH₃), 3.48 (1H, dd, J2.4, 9.2 Hz, H-4), 3.18 (1H, dd,

J2.6, 7.9 Hz, H-2). ¹³C NMR (125 MHz, CDCl₃) d: 138.8,

138.6 and 137.1 (Ph),134.8 (OCH₂CHCH₂), 128.5±127.4

Methyl 7-deoxy-2,3,4-tri-O-benzyl-7-(phenyldimethyl-

silyl)-l-glycero-b-d-allo-heptopyranoside (24). Column

chromatography, eluent hexane±ethyl acetate 6:1; yield

70%; colourless oil; [a]_D220.2 (c 1.4, CHCl₃); n_max

(®lm) 3517 (br), 3066, 3031, 2897, 1497, 1454, 1250,

1205, 1126, 1087, 838, 735, 699 cm²¹

;

¹H NMR

(500 MHz, CDCl₃) d: 7.55±7.19 (20H, m, 4Ph), 4.85±

4.42 (3£2H, 3ABq, 3CH₂Ph), 4.67 (1H, d, J7.9 Hz,

H-1), 4.07 (1H, dd, J2.4, 2.6 Hz, H-3), 4.08±4.03 (1H,

m, H-6), 3.68 (1H, dd, J1.2, 9.6 Hz, H-5), 3.49 (3H, s,

OCH₃), 3.46 (1H, dd, J2.4, 9.6 Hz, H-4), 3.12 (1H, dd,

J2.6, 7.9 Hz, H-2), 1.32 (1H, dd, J9.3, 14.6 Hz, H-7a),

9328

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

1

1.12 (1H, dd, J5.9, 14.6 Hz, H-7b), 0.34, 0.33 (2£3H, 2s,

(CH₃)₂Si). ¹³C NMR (125 MHz, CDCl₃) d: 139.2, 139.1,

138.6, 138.0, 133.6 and 128.8±127.3 (Ph), 102.0 (C-1),

78.9 (C-2), 76.0 (C-4), 75.1 (C-5), 75.0 (C-3), 74.3

(CH₂Ph), 72.8 (CH₂Ph), 71.8 (CH₂Ph), 67.3 (C-6), 56.9

(OCH₃), 21.9 (C-7), 22.1 and 22.6 [(CH₃)₂Si]. HR MS

(ESI): C₃₇H₄₄O₆Si1Na¹[M1Na]¹; Calcd: 635.2804.

Found: 635.2799. Anal. Calcd for C₃₇H₄₄O₆Si: C, 72.52;

H, 7.24. Found: C, 72.44; H, 7.41.

1159, 1072, 1030, 738, 698 cm²¹; H NMR (500 MHz,

CDCl₃) d: 7.38±7.25 (15H, m, 3Ph), 5.04±4.64 (3£2H,

3ABq, 3CH₂Ph), 4.58 (1H, d, J3.6 Hz, H-1), 4.02 (1H,

dd, J9.1, 9.6 Hz, H-3), 4.02±3.97 (1H, m, H-6), 3.77

(1H, dd, J4.2, 10.0 Hz, H-5), 3.58 (1H, dd, J9.1,

10.0 Hz, H-4), 3.51 (1H, dd, J3.6, 9.6 Hz, H-2), 3.45

(1H, dd, J6.9, 9.9 Hz, H-7a), 3.41 (1H, dd, J3.5,

9.9 Hz, H-7b), 3.39, 3.31 (2£3H, 2s, 2OCH₃). ¹³C NMR

(125 MHz, CDCl₃) d: 138.6, 138.1, 137.8 and 128.5±

127.6 (Ph), 97.8 (C-1), 82.4 (C-3), 80.1 (C-2), 79.0 (C-4),

75.7 (CH₂Ph), 74.7 (CH₂Ph), 73.3 (CH₂Ph), 73.2 (C-7), 71.6

(C-6), 69.8 (C-5), 59.0 and 55.2 (2OCH₃). HR MS (LSIMS):

C₃₀H₃₆O₇1Na¹[M1Na]¹; Calcd: 531.23587. Found:

531.23574.

Methyl 2,3,4,7-tetra-O-benzyl-d-glycero-a-d-gluco-hepto-

pyranoside (25). Column chromatography, eluent hexane±

ethyl acetate 3:1; yield 53%; colourless oil; [a]_D119.7 (c

1.7, CHCl₃); n_max(®lm) 3481 (br), 3089, 3064, 3031, 2917,

2870, 1497, 1454, 1361, 1209, 1195, 1160, 1072, 1030, 738,

698 cm²¹; ¹H NMR (500 MHz, CDCl₃) d: 7.38±7.15 (20H,

m, 4Ph), 5.02±4.42 (4£2H, 4ABq, 4CH₂Ph), 4.56 (1H, d,

J3.6 Hz, H-1), 4.07±4.03 (1H, m, H-6), 4.00 (1H, dd,

J9.6, 10.0 Hz, H-3), 3.76 (1H, dd, J3.7, 10.0 Hz, H-5),

3.55 (1H, dd, J10.0, 10.0 Hz, H-4), 3.54±3.47 (2H, m,

H-7a, H-7b), 3.49 (1H, dd, J3.6, 9.6 Hz, H-2), 3.35 (3H,

s, OCH₃). ¹³C NMR (125 MHz, CDCl₃) d: 138.6, 138.1,

138.0, 137.9 and 128.4±127.6 (Ph), 97.8 (C-1), 82.4

(C-3), 80.0 (C-2), 78.7 (C-4), 75.7 (CH₂Ph), 74.7

(CH₂Ph), 73.4 (CH₂Ph), 73.3 (CH₂Ph), 71.7 (C-6), 70.9

(C-7), 70.1 (C-5), 55.2 (OCH₃). ¹H NMR (500 MHz,

C₆D₆) d: 7.35±7.05 (20H, m, 4Ph), 5.04±4.33 (4£2H,

4ABq, 4CH₂Ph), 4.59 (1H, d, J3.5 Hz, H-1), 4.27±4.22

(1H, m, H-6), 4.23 (1H, dd, J9.0, 9.6 Hz, H-3), 4.03 (1H,

dd, J3.4, 10.0 Hz, H-5), 3.72 (1H, dd, J9.0, 10.0 Hz,

H-4), 3.68 (1H, dd, J6.9, 9.8 Hz, H-7a), 3.59 (1H, dd,

J3.8, 9.8 Hz, H-7b), 3.49 (1H, dd, J3.5, 9.6 Hz, H-2),

3.16 (3H, s, OCH₃). HR MS (LSIMS): C₃₆H₄₀O₇1Na¹

[M1Na]¹; Calcd: 607.26717. Found: 607.26958. Anal.

Calcd for C₃₆H₄₀O₇: C, 73.95; H, 6.90. Found: C, 73.69;

H, 6.82.

Methyl 2,3,4-tri-O-benzyl-7-O-methyl-l-glycero-a-d-gluco-

heptopyranoside (28). HPLC, eluent hexane±ethyl acetate

2:1; yield 35%; colourless needles, mp 83±848C (from

hexane±ether); [a]_D116.0 (c 1.4, CHCl₃); n_max(KBr)

3488 (br), 3063, 3029, 3002, 2938, 2897, 2866, 1498,

1455, 1360, 1117, 1072, 1056, 1029, 964, 740, 698 cm²¹

;

¹H NMR (500 MHz, CDCl₃) d: 7.37±7.24 (15H, m, 3Ph),

5.00±4.62 (3£2H, 3ABq, 3CH₂Ph), 4.57 (1H, d, J3.6 Hz,

H-1), 4.11±4.05 (1H, m, H-6), 3.98 (1H, dd, J9.0, 9.6 Hz,

H-3), 3.71 (1H, dd, J9.0, 10.00 Hz, H-4), 3.62 (1H, dd,

J1.0, 10.00 Hz, H-5), 3.51 (1H, dd, J8.1, 9.5 Hz, H-7a),

3.51 (1H, dd, J3.6, 9.6 Hz, H-2), 3.41 (1H, dd, J4.9,

9.5 Hz, H-7b), 3.35, 3.33 (2£3H, 2s, 2OCH₃). ¹³C NMR

(125 MHz, CDCl₃) d: 138.8, 138.3, 138.1 and 128.4±

127.5 (Ph), 98.3 (C-1), 82.1 (C-3), 79.7 (C-2), 77.1 (C-4),

75.7 (CH₂Ph), 75.1 (CH₂Ph), 74.0 (C-7), 73.4 (CH₂Ph), 69.6

(C-5), 67.4 (C-6), 59.0, 55.0 (2OCH₃). HR MS (LSIMS):

C₃₀H₃₆O₇1Na¹[M1Na]¹; Calcd: 531.23590. Found:

531.23458.

Methyl 7-O-allyl-2,3,4-tri-O-benzyl-d-glycero-a-d-gluco-

heptopyranoside (29). Column chromatography, eluent

hexane±ethyl acetate 3:1; yield 50%; colourless oil;

[a]_D123.5 (c 2.3, CHCl₃); n_max(®lm) 3482 (br), 3031,

Methyl 2,3,4,7-tetra-O-benzyl-l-glycero-a-d-gluco-hepto-

pyranoside (26). Column chromatography, eluent hexane±

ethyl acetate 3:1; yield 35%; colourless needles, mp 58±

598C (from hexane±ether), [a]_D14.9 (c 1.6, CHCl₃);

n_max(®lm) 3481 (br), 3089, 3064, 3031, 2929, 2865,

1497, 1454, 1361, 1165, 1136, 1102, 1053, 737,

2914, 1454, 1360, 1159, 1139, 1072, 1030, 738, 698 cm²¹

;

¹H NMR (500 MHz, CDCl₃) d: 7.37±7.24 (15H, m, 3Ph),

5.90±5.81 (1H, m, OCH₂CHvCH₂), 5.23±5.11 (2H, m,

OCH₂CHvCH₂), 5.02±4.63 (3£2H, 3ABq, 3CH₂Ph), 4.57

(1H, d, J3.6 Hz, H-1), 4.04±3.99 (1H, m, H-6), 4.01 (1H,

dd, J9.0, 10.0 Hz, H-3), 3.94±3.91 (2H, m,

OCH₂CHvCH₂), 3.77 (1H, dd, J3.9, 9.8 Hz, H-5), 3.58

(1H, dd, J9.0, 9.8 Hz, H-4), 3.50 (1H, dd, J3.6, 10.0 Hz,

H-2), 3.50±3.45 (2H, m, H-7a, H-7b), 3.38 (3H, s, OCH₃).

¹³C NMR (125 MHz, CDCl₃) d: 138.6, 138.0 and 137.9

(Ph), 134.5 (OCH₂CHvCH₂), 128.4±127.6 (Ph), 117.2

(OCH₂CHvCH₂), 97.8 (C-1), 82.3 (C-3), 80.0 (C-2), 78.8

(C-4), 75.6 (CH₂Ph), 74.7 (CH₂Ph), 73.2 (CH₂Ph), 72.3

(OCH₂CHvCH₂), 71.7 (C-6), 70.8 (C-7), 69.9 (C-5), 55.2

(OCH₃). HR MS (LSIMS): C₃₂H₃₈O₇1Na¹[M1Na]¹;

Calcd: 557.25152. Found: 557.25135.

698 cm²^{1 1}H NMR (500 MHz, CDCl₃) d: 7.40±7.20

;

(20H, m, 4Ph), 5.02±4.51 (4£2H, 4ABq, 4CH₂Ph), 4.58

(1H, d, J3.6 Hz, H-1), 4.19±4.12 (1H, m, H-6), 4.01

(1H, dd, J9.2, 9.5 Hz, H-3), 3.75 (1H, dd, J9.2,

10.00 Hz, H-4), 3.67 (1H, dd, J,1, 10.00 Hz, H-5), 3.64

(1H, dd, J8.1, 9.5 Hz, H-7a), 3.54 (1H, dd, J5.3,

9.5 Hz, H-7b), 3.53 (1H, dd, J3.6, 9.5 Hz, H-2), 3.31

(3H, s, OCH₃). ¹³C NMR (125 MHz, CDCl₃) d: 138.8,

138.3, 138.1, 137.9 and 128.4±127.5 (Ph), 98.3 (C-1),

82.1 (C-3), 79.7 (C-2), 77.2 (C-4), 75.7 (CH₂Ph), 75.1

(CH₂Ph), 73.4 (CH₂Ph), 73.4 (CH₂Ph), 71.6 (C-7), 69.6

(C-5), 67.6 (C-6), 55.1 (OCH₃). HR MS (LSIMS):

C₃₆H₄₀O₇1Na¹[M1Na]¹; Calcd: 607.26715. Found:

607.26970. Anal. Calcd for C₃₆H₄₀O₇: C, 73.95; H, 6.90.

Found: C, 73.65; H, 6.67.

Methyl 7-O-allyl-2,3,4-tri-O-benzyl-l-glycero-a-d-gluco-

heptopyranoside (30). Column chromatography, eluent

hexane±ethyl acetate 3:1; yield 41%; colourless needles,

mp 80±818C (from hexane±ethyl acetate), [a]_D19.6 (c

1.0, CHCl₃); n_max(KBr) 3489 (br), 3063, 3034, 2937, 2869,

1455, 1361, 1167, 1139, 1104, 1058, 1003, 948, 922, 739,

699 cm²¹; ¹H NMR (500 MHz, CDCl₃) d: 7.42±7.20 (15H,

Methyl 2,3,4-tri-O-benzyl-7-O-methyl-d-glycero-a-d-gluco-

heptopyranoside (27). HPLC eluent: hexane±ethyl acetate

2:1; yield 40%; colourless oil; [a]_D126.6 (c 1.6, CHCl₃);

n

_max(®lm) 3479 (br), 3064, 3031, 2924, 1454, 1360, 1195,

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

9329

m, 3Ph), 5.93±5.83 (1H, m, OCH₂CHvCH₂), 5.28±5.14

(2H, m, OCH₂CHvCH₂), 4.99±4.62 (3£2H, 3ABq,

3CH₂Ph), 4.57 (1H, d, J3.6 Hz, H-1), 4.14±4.07 (1H, m,

H-6), 4.03±3.95 (3H, m, H-3, OCH₂CHvCH₂), 3.72 (1H,

dd, J8.9, 10.0 Hz, H-4), 3.64 (1H, dd, J0.9, 10.0 Hz,

H-5), 3.56 (1H, dd, J8.0, 9.5 Hz, H-7a), 3.51 (1H, dd,

J3.6, 9.7 Hz, H-2), 3.47 (1H, dd, J5.0, 9.5 Hz, H-7b),

3.32 (3H, s, OCH₃). ¹³C NMR (125 MHz, CDCl₃) d: 138.8,

138.3 and 138.1 (Ph), 134.4 (OCH₂CHvCH₂), 128.4±127.5

(Ph), 117.2 (OCH₂CHvCH₂), 98.3 (C-1), 82.1 (C-3), 79.7

(C-2), 77.2 (C-4), 75.7 (CH₂Ph), 75.1 (CH₂Ph), 73.4

(CH₂Ph), 72.3 (OCH₂CHvCH₂), 71.4 (C-7), 69.6 (C-5),

67.5 (C-6), 55.1 (OCH₃). HR MS (LSIMS):

C₃₂H₃₈O₇1Na¹[M1Na]¹; Calcd: 557.25153. Found:

557.25514. Anal. Calcd for C₃₂H₃₈O₇: C, 71.89; H, 7.16.

Found: C, 71.77; H, 7.13.

NMR (500 MHz, CDCl₃) d: 7.40±7.22 (20H, m, 4Ph),

5.04±4.39 (4£2H, 4ABq, 4CH₂Ph), 4.74 (1H, d,

J3.6 Hz, H-1), 4.05 (1H, dd, J3.6, 10.0 Hz, H-2),

3.98±3.90 (1H, m, H-6), 3.94 (1H, dd, J2.7, 10.0 Hz,

H-3), 3.92±3.90 (1H, m, H-4), 3.81 (1H, dd, J,1, 4.4 Hz,

H-5), 3.46 (1H, dd, J6.1, 9.6 Hz, H-7a), 3.34 (3H, s,

OCH₃), 3.32 (1H, dd, J4.7, 9.6 Hz, H-7b). ¹³C NMR

(125 MHz, CDCl₃) d: 138.6, 138.4, 137.9, 137.9 and

128.4±127.5 (Ph), 98.8 (C-1), 79.3 (C-3), 77.3 (C-4), 76.1

(C-2), 74.4 (CH₂Ph), 73.7 (CH₂Ph), 73.5 (CH₂Ph), 73.4

(CH₂Ph), 71.0 (C-6), 69.8 (C-7), 68.9 (C-5), 55.3 (OCH₃).

HR MS (LSIMS): C₃₆H₄₀O₇1Na¹[M1Na]¹; Calcd:

607.26715. Found: 607.26602. Anal. Calcd for C₃₆H₄₀O₇:

C, 73.95; H, 6.90. Found: C, 73.79; H, 6.99.

Methyl

2,3,4-tri-O-benzyl-7-O-methyl-d-glycero-a-d-

galacto-heptopyranoside (34). Column chromatography,

eluent hexane±ethyl acetate 3:1; yield 75%; colourless oil;

[a]_D140.5 (c 2.41, CHCl₃); n_max(®lm) 3479 (br), 3031,

2923, 1497, 1454, 1351, 1194, 1116, 1055, 1028, 904, 783,

Methyl 7-deoxy-2,3,4-tri-O-benzyl-7-(phenyldimethyl-

silyl)-l-glycero-a-d-gluco-heptopyranoside (31). Column

chromatography, eluent hexane±ethyl acetate 8:1; yield

50%; colourless oil; [a]_D15.8 (c 0.8, CHCl₃); n_max

(®lm) 3513 (br), 3067, 3031, 2929, 1454, 1361, 1250,

1160, 1111, 1088, 1072, 1052, 1029, 914, 837, 734,

1

737, 698 cm²¹; H NMR (500 MHz, CDCl₃) d: 7.40±7.23

(15H, m, 3Ph), 5.01±4.67 (3£2H, 3ABq, 3CH₂Ph), 4.65

(1H, d, J3.7 Hz, H-1), 4.18±4.16 (1H, m, H-4), 4.04

(1H, dd, J3.7, 10.1 Hz, H-2), 3.93 (1H, dd, J2.8,

10.1 Hz, H-3), 3.94±3.89 (1H, m, H-6), 3.63 (1H, dd,

J,1, 9.1 Hz, H-5), 3.52 (1H, dd, J3.0, 9.6 Hz, H-7a),

3.46 (1H, dd, J5.2, 9.6 Hz, H-7b), 3.34, 3.32 (2£3H, 2s,

2OCH₃). ¹³C NMR (125 MHz, CDCl₃) d: 138.8, 138.7,

138.5 and 128.3±127.4 (Ph), 98.8 (C-1), 79.1 (C-3), 76.2

(C-2), 74.8 (CH₂Ph), 74.4 (C-4), 73.5 (CH₂Ph), 73.3 (C-7),

73.1 (CH₂Ph), 69.6 (C-5), 67.8 (C-6), 58.9 (OCH₃), 55.0

(OCH₃). HR MS (LSIMS): C₃₀H₃₆O₇1Na¹[M1Na]¹;

Calcd: 531.23590. Found: 531.23702.

1

698 cm²¹; H NMR (CDCl₃) d: 7.55±7.17 (20H, m, 4Ph),

5.00±4.58 (3£2H, 3ABq, 3CH₂Ph), 4.59 (1H, d, J3.6 Hz,

H-1), 4.04 (1H, ddd, J0.7, 3.9, 10.8 Hz, H-6), 3.97 (1H,

dd, J9.2, 9.6 Hz, H-3), 3.57 (1H, dd, J9.6, 9.6 Hz, H-4),

3.48 (1H, dd, J3.6, 9.6 Hz, H-2), 3.39 (1H, dd, J0.7,

9.6 Hz, H-5), 3.34 (3H, s, OCH₃), 1.34 (1H, dd, J10.8,

14.9 Hz, H-7a), 0.90 (1H, dd, J3.9, 14.9 Hz, H-7b),

0.34, 0.33 (2£3H, 2s, (CH₃)₂Si). ¹³C NMR (125 MHz,

CDCl₃) d: 139.1, 138.8, 138.2, 138.1, 133.6 and 128.9±

127.6 (Ph), 98.2 (C-1), 82.1 (C-3), 80.0 (C-2), 77.8 (C-4),

75.7 (CH₂Ph), 75.2 (CH₂Ph), 74.1 (C-5), 73.4 (CH₂Ph), 66.7

(C-6), 55.2 (OCH₃), 21.6 (C-7), 22.1 and 22.4 [(CH₃)₂Si].

HR MS (LSIMS): C₃₇H₄₄O₆Si1Na¹[M1Na]¹; Calcd:

635.28049. Found: 635.28177.

Methyl

2,3,4-tri-O-benzyl-7-O-methyl-l-glycero-a-d-

galacto-heptopyranoside (35). Column chromatography,

eluent hexane±ethyl acetate 3:1; yield 17%; colourless oil;

[a]_D115.1 (c 0.84, CHCl₃); n_max(®lm) 3493 (br), 3031,

2900, 1497, 1455, 1351, 1196, 1128, 1099, 1048, 970, 782,

Methyl 2,3,4,7-tetra-O-benzyl-d-glycero-a-d-galacto-hepto-

pyranoside (32). Column chromatography, eluent hexane±

ethyl acetate 7:2; yield 48%; colourless oil; [a]_D132.0 (c

1.64, CHCl₃); n_max(®lm) 3487 (br), 3031, 2912, 2865, 1497,

1

737, 698 cm²¹; H NMR (500 MHz, CDCl₃) d: 7.41±7.25

(15H, m, 3Ph), 5.10±4.64 (3£2H, 3ABq, 3CH₂Ph), 4.75

(1H, d, J3.6 Hz, H-1), 4.06 (1H, dd, J3.6, 10.8 Hz,

H-2), 3.96 (1H, dd, J2.8, 10.8 Hz, H-3), 3.97±3.96 (1H,

m, H-4), 3.95±3.90 (1H, m, H-6) 3.75 (1H, dd, J,1, 4.1 Hz,

H-5), 3.36 (3H, s, OCH₃), 3.34 (1H, dd, J6.0, 9.6 Hz,

H-7a), 3.29 (3H, s, OCH₃), 3.23 (1H, dd, J5.0, 9.6 Hz,

H-7b). ¹³C NMR (125 MHz, CDCl₃) d: 138.6, 138.3,

137.8 and 128.4±127.5 (Ph), 98.7 (C-1), 79.3 (C-3), 77.4

(C-4), 76.1 (C-2), 74.4 (CH₂Ph), 73.7 (CH₂Ph), 73.5

(CH₂Ph), 72.5 (C-7), 70.8 (C-6), 68.8 (C-5), 59.0 (OCH₃),

55.2 (OCH₃). HR MS (LSIMS): C₃₀H₃₆O₇1Na¹[M1Na]¹;

Calcd: 531.23590. Found: 531.23608.

1454, 1353, 1196, 1105, 1054, 1028, 906, 737, 698 cm²¹

;

¹H NMR (500 MHz, CDCl₃) d: 7.40±7.20 (20H, m, 4Ph),

5.01±4.46 (4£2H, 4ABq, 4CH₂Ph), 4.63 (1H, d, J3.6 Hz,

H-1), 4.18±4.16 (1H, m, H-4), 4.03 (1H, dd, J3.6,

10.1 Hz, H-2), 3.99±3.92 (1H, m, H-6), 3.92 (1H, dd,

J2.8, 10.1 Hz, H-3), 3.67 (1H, dd, J,1, 8.8 Hz, H-5),

3.65 (1H, dd, J3.1, 9.5 Hz, H-7a), 3.58 (1H, dd, J5.2,

9.5 Hz, H-7b), 3.28 (3H, s, OCH₃). ¹³C NMR (125 MHz,

CDCl₃) d: 138.8, 138.8, 138.5, 137.8 and 128.4±127.5 (Ph),

98.9 (C-1), 79.2 (C-3), 76.2 (C-2), 74.8 (CH₂Ph), 74.5 (C-4),

73.5 (CH₂Ph), 73.4 (CH₂Ph), 73.1 (CH₂Ph), 71.1 (C-7), 69.7

(C-5), 68.1 (C-6), 55.2 (OCH₃). HR MS (LSIMS):

C₃₆H₄₀O₇1Na¹[M1Na]¹; Calcd: 607.26717. Found:

607.26607. Anal. Calcd for C₃₆H₄₀O₇: C, 73.95; H, 6.90.

Found: C, 74.00; H, 6.85.

Methyl 7-O-allyl-2,3,4-tri-O-benzyl-d-glycero-a-d-galacto-

heptopyranoside (36). Column chromatography, eluent

hexane±ethyl acetate 7:2; yield 69%; colourless oil;

[a]_D135.7 (c 1.81, CHCl₃); n_max(®lm) 3481 (br), 3064,

3031, 2914, 1497, 1454, 1351, 1195, 1105, 1055, 1028, 934,

1

Methyl 2,3,4,7-tetra-O-benzyl-l-glycero-a-d-galacto-hepto-

pyranoside (33). Column chromatography, eluent hexane±

ethyl acetate 7:2; yield 32%; colourless oil; [a]_D111.2 (c

2.41, CHCl₃); n_max(®lm) 3494 (br), 3031, 2908, 1497, 1454,

904, 784, 737, 698 cm²¹; H NMR (500 MHz, CDCl₃) d:

7.40±7.23 (15H, m, 3Ph), 5.91±5.82 (1H, m,

OCH₂CHCH₂), 5.27±5.15 (2H, m, OCH₂CHCH₂), 5.02±

4.66 (3£2H, 3ABq, 3CH₂Ph), 4.64 (1H, d, J3.6 Hz,

H-1), 4.19±4.17 (1H, m, H-4), 4.04 (1H, dd, J3.6,

1

1351, 1195, 1130, 1099, 1049, 782, 737, 698 cm²¹; H

9330

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

10.1 Hz, H-2), 4.02±3.91 (3H, m, H-6, OCH₂CHCH₂), 3.93

(1H, dd, J2.8, 10.1 Hz, H-3), 3.65 (1H, dd, J,1, 9.0 Hz,

H-5), 3.59 (1H, dd, J3.1, 9.6 Hz, H-7a), 3.52 (1H, dd,

J5.2, 9.6 Hz, H-7b), 3.32 (3H, s, OCH₃). ¹³C NMR

(125 MHz, CDCl₃) d: 138.8, 138.8 and 138.5 (Ph), 134.4

(OCH₂CHCH₂), 128.3±127.4 (Ph), 117.2 (OCH₂CHCH₂),

98.8 (C-1), 79.2 (C-3), 76.2 (C-2), 74.8 (CH₂Ph), 74.5

(C-4), 73.5 (CH₂Ph), 73.1 (CH₂Ph), 72.2 (OCH₂CHCH₂),

70.9 (C-7), 69.7 (C-5), 68.0 (C-6), 55.1 (OCH₃). HR MS

(LSIMS): C₃₂H₃₈O₇1Na¹[M1Na]¹; Calcd: 557.25152.

Found: 557.25052.

dd, J3.7, 10.1 Hz, H-2), 3.96 (1H, ddd, J3.3, 6.4,

10.8 Hz, H-6), 3.91±3.89 (1H, m, H-4), 3.85 (1H, dd,

J2.6, 10.1 Hz, H-3), 3.36±3.34 (1H, m, H-5), 3.35 (3H,

s, OCH₃), 0.92 (1H, dd, J10.8, 14.4 Hz, H-7a), 0.73±0.67

(1H, m, H-7b), 0.32, 0.31 (2£3H, 2s, (CH₃)₂Si). ¹³C NMR

(125 MHz, CDCl₃) d: 139.5, 138.7, 138.3, 138.0, 133.6 and

128.8±127.4 (Ph), 98.7 (C-1), 79.6 (C-3), 76.2 (C-2), 75.8

(C-4),75.3 (C-5), 74.4 (CH₂Ph), 73.7 (CH₂Ph), 73.5

(CH₂Ph), 68.9 (C-6), 55.4 (OCH₃), 19.8 (C-7), 21.7 and

22.4 [(CH₃)₂Si]. HR MS (LSIMS): C₃₇H₄₄O₆Si1Na¹

[M1Na]¹; Calcd: 635.28052. Found: 635.27944. Anal.

Calcd for C₃₇H₄₄O₆Si: C, 72.52; H, 7.24. Found: C, 72.34;

H, 7.21.

Methyl 7-O-allyl-2,3,4-tri-O-benzyl-l-glycero-a-d-galacto-

heptopyranoside (37). Column chromatography, eluent

hexane±ethyl acetate 7:2; yield 18%; colourless oil;

[a]_D116.2 (c 1.39, CHCl₃); n_max(®lm) 3492 (br), 3064,

3031, 2909, 1497, 1454, 1350, 1195, 1131, 1099, 1049, 929,

782, 737, 698 cm²¹; ¹H NMR (500 MHz, CDCl₃) d: 7.41±

7.24 (15H, m, 3Ph), 5.89±5.80 (1H, m, OCH₂CHCH₂),

5.25±5.14 (2H, m, OCH₂CHCH₂), 5.09±4.64 (3£2H,

3ABq, 3CH₂Ph), 4.75 (1H, d, J3.6 Hz, H-1), 4.06 (1H,

dd, J3.6, 10.0 Hz, H-2), 4.00±3.98 (1H, m, H-4), 3.96

(1H, dd, J2.7, 10.0 Hz, H-3), 3.98±3.89 (3H, m, H-6,

OCH₂CHCH₂), 3.79 (1H, dd, J,1, 3.7 Hz, H-5), 3.41

(1H, dd, J6.3, 9.6 Hz, H-7a), 3.36 (3H, s, OCH₃), 3.31

(1H, dd, J5.0, 9.6 Hz, H-7b). ¹³C NMR (125 MHz,

CDCl₃) d: 138.6, 138.3 and 137.9 (Ph), 134.4

(OCH₂CHCH₂), 128.4±127.5 (Ph), 117.3 (OCH₂CHCH₂),

98.8 (C-1), 79.3 (C-3), 77.5 (C-4), 76.1 (C-2), 74.4

7-O-Benzyl-1,2:3,4-di-O-isopropylidene-d-glycero-a-d-

galacto-heptopyranose (40). HPLC eluent: hexane±ethyl

acetate 5:2; yield: 43%; colourless oil; [a]_D250.6 (c

1.3, CHCl₃); n_max(®lm) 3496 (br), 2988, 2937, 1497,

1455, 1382, 1256, 1170, 1104, 1001, 898, 805, 739,

1

699 cm²¹; H NMR (500 MHz, CDCl₃) d: 7.35±7.20 (5H,

m, Ph), 5.51 (1H, d, J5.0 Hz, H-1), 4.62 (1H, dd, J2.4,

8.0 Hz, H-3), 4.58 (2H, s, CH₂Ph), 4.47 (1H, dd, J1.9,

8.0 Hz, H-4), 4.31 (1H, dd, J2.4, 5.0 Hz, H-2), 4.02±

3.95 (1H, m, H-6), 3.83 (1H, dd, J1.9, 8.7 Hz, H-5),

3.74 (1H, dd, J3.3, 9.8 Hz, H-7a), 3.65 (1H, dd, J5.3,

9.8 Hz, H-7b), 1.49, 1.46, 1.37, 1.32 (4£3H, 4s,

2£(CH₃)₂C). ¹³C NMR (125 MHz, CDCl₃) d: 138.1,

128.3, 127.6 and 127.6 (Ph), 109.2 and 108.7

(2£(CH₃)₂C), 96.3 (C-1), 73.4 (CH₂Ph), 71.2 (C-7), 70.8

(C-4), 70.7 (C-2), 70.6 (C-3), 68.9 (C-6), 67.0 (C-5), 26.0,

25.9, 25.0 and 24.4 (2£(CH₃)₂C). HR MS (LSIMS):

C₂₀H₂₈O₇1Na¹[M1Na]¹; Calcd: 403.17327. Found:

403.17489. Anal. Calcd for C₂₀H₂₈O₇: C, 63.14; H, 7.42.

Found: C, 62.89; H, 7.61.

(CH₂Ph),

73.7

(CH₂Ph),

73.5

(CH₂Ph),

72.3

(OCH₂CHCH₂), 71.0 (C-6), 69.9 (C-7), 68.7 (C-5), 55.2

(OCH₃). HR MS (LSIMS): C₃₂H₃₈O₇1Na¹[M1Na]¹;

Calcd: 557.25152. Found: 557.25110.

Methyl 7-deoxy-2,3,4-tri-O-benzyl-7-(phenyldimethyl-

silyl)-d-glycero-a-d-galacto-heptopyranoside (38). HPLC

eluent: hexane±CH₂Cl₂±ether 10:20:1; yield: 1.3%; colour-

less oil; [a]_D110.5 (c 0.43, CHCl₃); n_max(®lm) 3579,

3491 (br), 3066, 3031, 2911, 1454, 1351, 1248, 1196,

7-O-Benzyl-1,2:3,4-di-O-isopropylidene-l-glycero-a-d-

galacto-heptopyranose (41). HPLC eluent: hexane±ethyl

acetate 5:2; yield: 37%; colourless oil; [a]_D244.6 (c

2.22, CHCl₃); n_max(®lm) 3523 (br), 2988, 2936, 1497,

1455, 1383, 1256, 1213, 1169, 1114, 1070, 1004, 901,

1112, 1053, 1029, 835, 779, 735, 699 cm²^{1 1}H NMR

;

(500 MHz, CDCl₃) d: 7.51±7.24 (20H, m, 4Ph), 4.95±

4.64 (3£2H, 3ABq, 3CH₂Ph), 4.66 (1H, d, J3.7 Hz,

H-1), 4.03 (1H, dd, J3.7, 10.1 Hz, H-2), 4.03±4.00 (1H,

m, H-4), 3.81 (1H, dd, J2.7, 10.1 Hz, H-3), 3.81±3.74

(1H, m, H-6), 3.32 (3H, s, OCH₃), 3.22 (1H, dd, J,1,

7.6 Hz, H-5), 1.22 (1H, dd, J3.6, 14.8 Hz, H-7a), 0.81

(1H, dd, J10.9, 14.8 Hz, H-7b), 0.27, 0.26 (2£3H, 2s,

(CH₃)₂Si). ¹³C NMR (CDCl₃) d: 139.3, 138.8, 138.5,

138.4, 133.6 and 129.0±127.6 (Ph), 98.8 (C-1), 79.6

(C-3), 76.6 (C-2), 74.4 (C-5), 74.1 (CH₂Ph), 73.6

(CH₂Ph), 73.5 (CH₂Ph), 73.1 (C-4), 67.8 (C-6), 55.2

(OCH₃), 21.5 (C-7), 22.0 and 22.5 [(CH₃)₂Si]. HR MS

(ESI): C₃₇H₄₄O₆Si1Na¹[M1Na]¹; Calcd: 635.2799.

Found: 635.2774.

835, 738, 699 cm²^{1 1}H NMR (500 MHz, CDCl₃) d:

;

7.35±7.20 (5H, m, Ph), 5.60 (1H, d, J5.0 Hz, H-1), 4.63

(1H, d, J11.9 Hz, CHHPh), 4.58 (1H, dd, J2.4, 8.0 Hz,

H-3), 4.53 (1H, d, J11.9 Hz, CHHPh), 4.32 (1H, dd,

J2.4, 5.0 Hz, H-2), 4.26 (1H, dd, J1.8, 8.0 Hz, H-4),

4.08±4.04 (1H, m, H-6), 3.96 (1H, dd, J1.8, 5.1 Hz,

H-5), 3.69 (1H, dd, J5.5, 9.9 Hz, H-7a), 3.63 (1H, dd,

J4.5, 9.9 Hz, H-7b), 1.49, 1.46, 1.33, 1.31 (4£3H, 4s,

2£(CH₃)₂C). ¹³C NMR (CDCl₃) d: 138.2, 128.3, 127.7

and 127.5 (Ph), 109.5 and 108.8 (2£(CH₃)₂C), 96.5 (C-1),

73.5 (CH₂Ph), 72.6 (C-4), 70.9 (C-3), 70.7 (C-6), 70.7 (C-2),

69.9 (C-7), 66.9 (C-5), 25.9, 25.8, 25.0 and 24.1

(2£(CH₃)₂C). HR MS (LSIMS): C₂₀H₂₈O₇1Na¹

[M1Na]¹; Calcd: 403.17327. Found: 403.17498. Anal.

Calcd for C₂₀H₂₈O₇: C, 63.14; H, 7.42. Found: C, 63.15;

H, 7.35.

Methyl 7-deoxy-2,3,4-tri-O-benzyl-7-(phenyldimethyl-

silyl)-l-glycero-a-d-galacto-heptopyranoside (39). HPLC

eluent: hexane±CH₂Cl₂±ether 10:20:1; yield: 81%; colour-

less oil; [a]_D27.5 (c 1.2, CHCl₃); n_max(®lm) 3576, 3510

(br), 3066, 3031, 2907, 1454, 1350, 1248, 1198, 1132, 1112,

1,2:3,4-Di-O-isopropylidene-7-O-methyl-d-glycero-a-d-

galacto-heptopyranose (42). HPLC eluent: hexane±ethyl

acetate 2:1; yield: 67%; colourless oil; [a]_D251.9 (c

1.59, CHCl₃); n_max(®lm) 3493 (br), 2987, 2937, 1457,

1382, 1256, 1213, 1170, 1109, 1067, 1002, 898,

1049, 1029, 945, 834, 783, 735, 699 cm²^{1 1}H NMR

;

(CDCl₃) d: 7.51±7.18 (20H, m, 4Ph), 4.99±4.53 (3£2H,

1

3ABq, 3CH₂Ph), 4.70 (1H, d, J3.7 Hz, H-1), 4.02 (1H,

776 cm²¹; H NMR (500 MHz, CDCl₃) d: 5.50 (1H, d,

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

9331

J4.9 Hz, H-1), 4.63 (1H, dd, J2.4, 8.0 Hz, H-3), 4.48

(1H, dd, J1.8, 8.0 Hz, H-4), 4.31 (1H, dd, J2.4,

4.9 Hz, H-2), 3.97±3.90 (1H, m, H-6), 3.78 (1H, dd,

J1.8, 8.8 Hz, H-5), 3.64 (1H, dd, J3.0, 9.8 Hz, H-7a),

3.50 (1H, dd, J5.7, 9.8 Hz, H-7b), 3.40 (3H, s, OCH₃),

1.53, 1.46, 1.37, 1.33 (4£3H, 4s, 2£(CH₃)₂C). ¹³C NMR

(125 MHz, CDCl₃) d: 109.2 and 108.7 (2£(CH₃)₂C), 96.3

(C-1), 73.4 (C-7), 70.7 (C-2), 70.7 (C-4), 70.6 (C-3), 68.7

(C-6), 67.0 (C-5), 59.0 (OCH₃), 25.9, 25.9, 25.0, 24.4

(2£(CH₃)₂C). HR MS (LSIMS): C₁₄H₂₄O₇1Na¹

[M1Na]¹; Calcd: 327.14197. Found: 327.14115. Anal.

Calcd for C₁₄H₂₄O₇: C, 55.25; H, 7.95. Found: C, 54.93;

H, 8.01.

n_max(®lm) 3525 (br), 2988, 2937, 1383, 1255, 1213,

1

1169, 1070, 1003, 901 cm²¹; H NMR (CDCl₃) d: 5.97±

5.88 (1H, m, OCH₂CHCH₂), 5.63 (1H, d, J5.0 Hz, H-1),

5.32±5.16 (2H, m, OCH₂CHCH₂), 4.64 (1H, dd, J2.4,

8.0 Hz, H-3), 4.37 (1H, dd, J1.8, 8.0 Hz, H-4), 4.36 (1H,

dd, J2.4, 5.0 Hz, H-2), 4.12±4.01 (3H, m, H-6,

OCH₂CHCH₂), 3.95 (1H, dd, J1.8, 4.6 Hz, H-5), 3.65

(1H, dd, J5.8, 9.8 Hz, H-7a), 3.61 (1H, dd, J4.7,

9.8 Hz, H-7b), 1.55, 1.50, 1.37, 1.36 (4£3H, 4s,

2£(CH₃)₂C). ¹³C NMR (125 MHz, CDCl₃) d: 134.5

(OCH₂CHCH₂), 116.9 (OCH₂CHCH₂), 109.5, 108.8

(2£(CH₃)₂C), 96.5 (C-1), 72.9 (C-4), 72.4 (OCH₂CHCH₂),

71.0 (C-3), 70.7 (C-6), 70.6 (C-2), 69.7 (C-7), 66.6 (C-5),

25.9, 25.8, 25.0 and 24.2 (2£(CH₃)₂C). HR MS (LSIMS):

C₁₆H₂₆O₇1Na¹[M1Na]¹; Calcd: 353.15762. Found:

353.15932. Anal. Calcd for C₁₆H₂₆O₇: C, 58.17; H, 7.93.

Found: C, 58.01; H, 8.10.

1,2:3,4-Di-O-isopropylidene-7-O-methyl-l-glycero-a-d-

galacto-heptopyranose (43). HPLC eluent: hexane±ethyl

acetate 2:1; yield: 15%; colourless oil; [a]_D252.6 (c

1.82, CHCl₃); n_max(®lm) 3519 (br), 2988, 2936, 1458,

1

1383, 1256, 1213, 1170, 1070, 1003, 901, 778 cm²¹; H

7-Deoxy-1,2:3,4-di-O-isopropylidene-7-(phenyldimethyl-

silyl)-d-glycero-a-d-galacto-heptopyranose (46). Column

chromatography, eluent hexane±ethyl acetate 8:1; yield

40%; colourless oil; [a]_D252.3 (c 1.09, CHCl₃); lit.³¹:

[a]_D252.9 (c 1, CHCl₃);n_max(®lm) 3504 (br), 2989,

2937, 1428, 1382, 1255, 1212, 1113, 1071, 1001, 900,

NMR (500 MHz, CDCl₃) d: 5.60 (1H, d, J5.0 Hz, H-1),

4.62 (1H, dd, J2.4, 8.0 Hz, H-3), 4.34 (1H, dd, J2.4,

5.0 Hz, H-2), 4.33 (1H, dd, J1.7, 8.0 Hz, H-4), 4.05±

4.00 (1H, m, H-6), 3.89 (1H, dd, J1.7, 4.9 Hz, H-5),

3.57 (1H, dd, J5.3, 9.8 Hz, H-7a), 3.55 (1H, dd, J5.0,

9.8 Hz, H-7b), 3.40 (3H, s, OCH₃), 1.54, 1.48, 1.35, 1.34

(4£3H, 4s, 2£(CH₃)₂C). ¹³C NMR (125 MHz, CDCl₃) d:

109.6 and 108.8 (2£(CH₃)₂C), 96.4 (C-1), 72.7 (C-4), 72.3

(C-7), 70.9 (C-3), 70.6 (C-2), 70.6 (C-6), 66.7 (C-5), 59.2

(OCH₃), 25.9, 25.8, 25.0 and 24.2 (2£(CH₃)₂C). HR MS

(LSIMS): C₁₄H₂₄O₇1Na¹[M1Na]¹; Calcd: 327.14197.

Found: 327.14176. Anal. Calcd for C₁₄H₂₄O₇: C, 55.25; H,

7.95. Found: C, 54.96; H, 7.88.

831, 730, 701 cm²^{1 1}H NMR (500 MHz, CDCl₃) d:

;

7.62±7.35 (5H, m, Ph), 5.58 (1H, d, J5.1 Hz, H-1), 4.61

(1H, dd, J2.4, 8.0 Hz, H-3), 4.48 (1H, dd, J2.0, 8.0 Hz,

H-4), 4.33 (1H, dd, J2.4, 5.1 Hz, H-2), 4.04±3.95 (1H, m,

H-6), 3.51 (1H, dd, J2.0, 7.2 Hz, H-5), 1.54, 1.47 (2£3H,

2s, (CH₃)₂C), 1.40 (1H, dd, J3.3, 14.9 Hz, H-7a), 1.37,

1.35 (2£3H, 2s, (CH₃)₂C), 1.06 (1H, dd, J10.9, 14.9 Hz,

H-7b), 0.41, 0.39 (2£3H, 2s, (CH₃)₂Si). ¹³C NMR

(125 MHz, CDCl₃) d: 139.3, 133.6, 128.8 and 127.7 (Ph),

109.3 and 108.5 (2£(CH₃)₂C), 96.5 (C-1), 72.0 (C-5),

70.9 (C-4), 70.8 (C-3), 70.4 (C-2), 69.0 (C-6), 26.1, 25.9,

25.0 and 24.5 (2£(CH₃)₂C), 21.9 (C-7), 22.1, 22.2

[(CH₃)₂Si]. HR MS (LSIMS): C₂₁H₃₂O₆Si1Na¹

[M1Na]¹; Calcd: 431.18658. Found: 431.18901. Anal.

Calcd for C₂₁H₃₂O₆Si: C, 61.73; H, 7.90. Found: C, 61.76;

H, 7.95.

7-O-Allyl-1,2:3,4-di-O-isopropylidene-d-glycero-a-d-

galacto-heptopyranose (44). (44145 formed an insepar-

able mixture which was separated after conversion to 6-O-

benzoates 71 and 72 respectively; separation by HPLC with

hexane±ethyl acetate 6:1, then hydrolysis with MeONa in

methanol); yield: 62%; colourless oil; [a]_D251.6 (c 1.23,

CHCl₃); n_max(®lm) 3496 (br), 2988, 2938, 1457, 1382,

1

1256, 1213, 1170, 1069, 1002, 929, 898, 777 cm²¹; H

NMR (500 MHz, CDCl₃) d: 5.97±5.88 (1H, m,

OCH₂CHCH₂), 5.52 (1H, d, J5.0 Hz, H-1), 5.32±5.16

(2H, m, OCH₂CHCH₂), 4.65 (1H, dd, J2.4, 8.0 Hz, H-3),

4.51 (1H, dd, J1.8, 8.0 Hz, H-4), 4.33 (1H, dd, J2.4,

5.0 Hz, H-2), 4.10±4.03 (2H, m, OCH₂CHCH₂), 3.97 (1H,

ddd, J3.2, 5.3, 8.8 Hz, H-6), 3.83 (1H, dd, J1.8, 8.8 Hz,

H-5), 3.70 (1H, dd, J3.2, 9.8 Hz, H-7a), 3.60 (1H, dd,

J5.3, 9.8 Hz, H-7b), 1.54, 1.48, 1.39, 1.35 (4£3H, 4s,

2£(CH₃)₂C). ¹³C NMR (125 MHz, CDCl₃) d: 134.6

(OCH₂CHCH₂), 116.9 (OCH₂CHCH₂), 109.2 and 108.7

(2£(CH₃)₂C), 96.3 (C-1), 72.2 (OCH₂CHCH₂), 70.8 (C-7),

70.7 and 70.7 (C-4, C-2), 70.6 (C-3), 68.8 (C-6), 66.9 (C-5),

26.0, 26.0, 25.0 and 24.4 (2£(CH₃)₂C). HR MS (LSIMS):

C₁₆H₂₆O₇1Na¹[M1Na]¹; Calcd: 353.15762. Found:

353.15629. Anal. Calcd for C₁₆H₂₆O₇: C, 58.17; H, 7.93.

Found: C, 58.07; H, 8.09.

7-Deoxy-1,2:3,4-di-O-isopropylidene-7-(phenyldimethyl-

silyl)-l-glycero-a-d-galacto-heptopyranose (47). Column

chromatography, eluent hexane±ethyl acetate 8:1; yield

36%; colourless oil; [a]_D268.2 (c 1.62, CHCl₃); lit.³¹:

[a]_D268.2 (c 1, CHCl₃); n_max(®lm) 3510 (br), 2989,

2934, 1381, 1254, 1213, 1111, 1074, 999, 901, 830, 729,

1

700 cm²¹; H NMR (500 MHz, CDCl₃) d: 7.64±7.36 (5H,

m, Ph), 5.62 (1H, d, J5.0 Hz, H-1), 4.59 (1H, dd, J2.3,

8.0 Hz, H-3), 4.34 (1H, dd, J2.3, 5.0 Hz, H-2), 4.32 (1H,

dd, J1.8, 8.0 Hz, H-4), 4.05 (1H, ddd, J2.9, 6.0, 11.1 Hz,

H-6), 3.51 (1H, dd, J1.8, 6.0 Hz, H-5), 1.54, 1.46, 1.36,

1.35 (4£3H, 4s, 2£(CH₃)₂C), 1.17 (1H, dd, J11.1,

14.4 Hz, H-7a), 1.05 (1H, dd, J2.9, 14.4 Hz, H-7b),

0.43, 0.40 (2£3H, 2s, (CH₃)₂Si). ¹³C NMR (125 MHz,

CDCl₃) d: 139.8, 133.6, 128.7 and 127.6 (Ph), 109.3 and

108.5 (2£(CH₃)₂C), 96.4 (C-1), 72.9 (C-5), 71.8 (C-4), 70.9

(C-3), 70.6 (C-2), 68.8 (C-6), 26.1, 25.9, 24.9 and 24.2

(2£(CH₃)₂C), 19.5 (C-7), 21.3, 22.5 [(CH₃)₂Si]. HR MS

(LSIMS): C₂₁H₃₂O₆Si1Na¹[M1Na]¹; Calcd: 431.18658.

Found: 431.18714. Anal. Calcd for C₂₁H₃₂O₆Si: C, 61.73;

H, 7.90. Found: C, 61.72; H, 8.13.

7-O-Allyl-1,2:3,4-di-O-isopropylidene-l-glycero-a-d-

galacto-heptopyranose (45). (Second component of the

mixture 44145, separated as 6-O-benzoate 72 by HPLC

with hexane±ethyl acetate 6:1, then Zemplen hydrolysis);

yield: 17%; colourless oil; [a]_D246.4 (c 1.58, CHCl₃);

9332

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

Determination of con®guration of heptoses

J2.4, 9.6 Hz, H-4), 3.53 (3H, s, OCH₃), 3.30 (1H, dd,

J2.5, 7.9 Hz, H-2). ¹³C NMR (50 MHz, CDCl₃) d:

138.8, 138.6, 138.3, 137.7 and 128.3±127.4 (Ph), 102.5

(C-1), 78.7, 75.8, 75.4, 74.8 and 74.4 (C-2,3,4,5,6), 74.5,

73.0, 72.1, 70.9 and 62.7 (C-7, 4CH₂Ph), 56.9 (OCH₃). HR

MS (LSIMS): C₃₆H₄₀O₇1Na¹[M1Na]¹; Calcd:

607.26717. Found: 607.26760.

Methyl 2,3,4,6-tetra-O-benzyl-7-O-methyl-l-glycero-b-

d-allo-heptopyranoside (48). To a cooled (08C) solution

of 18 (100 mg, 0.20 mmol) in abs DMF (1 ml) was added

NaH (suspension in mineral oil, 5 mg, 0.22 mmol). The

suspension was stirred for 10 min and a solution of benzyl

bromide (37 mg, 0.22 mmol) was added. Stirring was

continued for 8 h whereupon the excess of the hydride

was decomposed with MeOH and the mixture was poured

into ice-water. The product was extracted with ether, and the

organic extract was dried and concentrated to dryness. The

residue was puri®ed by chromatography in 6:1 hexane±

EtOAc to yield 48 (100 mg, 85%) as a colourless oil;

[a]_D113.2 (c 1.1, CHCl₃); n_max(®lm) 3064, 3031,

2893, 1497, 1454, 1349, 1308, 1206, 1128, 1094, 1029,

Methyl 2,3,4-tri-O-benzyl-l-glycero-b-d-allo-heptopyra-

noside (51). To a solution of 22 (300 mg, 0.56 mmol) in a

mixture of EtOH (9 ml), benzene (2 ml) and water (1 ml)

was added 1,4-diazabicyclo[2.2.2]octane (DABCO, 18 mg),

and the solution was heated to 808C. Wilkinson's catalyst

(37 mg) was added and the mixture was re¯uxed for 3 h and

left at room temperature overnight. The mixture was ®ltered

and the ®ltrate was concentrated under lowered pressure.

The remaining oil was dissolved in 10:1 acetone±water,

and HgO (153 mg) and HgCl₂(187 mg) were added. The

suspension was stirred (0.5 h) at room temperature, then

®ltered, the ®ltrate was concentrated, and the residue was

dissolved in ether. The ether solution was washed with aq

50% KI, aq 10% NaHSO₃, and aq 1% NaHCO₃, dried, and

concentrated. The residue was chromatographed with 1:2

hexane±EtOAc to yield 51 (196 mg, 71%) as an amorphous

solid; [a]_D11.0 (c 1.0, CHCl₃); n_max(®lm) 3385 (br),

3308 (br), 3032, 2965, 2915, 1454, 1206, 1134, 1096,

1

737, 698 cm²¹; H NMR (200 MHz, CDCl₃) d: 7.41±7.14

(20H, m, 4Ph), 4.92±4.14 (4£2H, 4ABq, 4CH₂Ph), 4.78

(1H, d, J7.8 Hz, H-1), 4.20±4.14 (1H, m, H-3), 4.08±

3.98 (2H, m, H-5, H-6), 3.77±3.60 (3H, m, H-4, H-7a,

H-7b), 3.53, 3.36 (2£3H, 2s, 2OCH₃), 3.28 (1H, dd,

J2.4, 7.8 Hz, H-2). ¹³C NMR (50 MHz, CDCl₃) d:

139.0, 138.8, 138.8, 138.0 and 128.2±127.3 (Ph), 102.2

(C-1), 78.9, 75.5, 75.5, 74.6 and 73.1 (C-2,3,4,5,6), 74.4,

73.2, 73.1, 72.9 and 70.8 (C-7, 4CH₂Ph), 59.1 and 56.6

(2OCH₃). HR MS (LSIMS): C₃₇H₄₂O₇1Na¹[M1Na]¹;

Calcd: 621.28282. Found: 621.28272. Anal. Calcd for

C₃₇H₄₂O₇: C, 74.22; H, 7.07. Found: C, 74.20; H, 6.88.

1

1047, 1026, 741, 697 cm²¹; H NMR (200 MHz, CDCl₃)

d: 7.42±7.25 (15H, m, 3Ph), 4.93±4.45 (3£2H, 3ABq,

3CH₂Ph), 4.85 (1H, d, J7.9 Hz, H-1), 4.12 (1H, dd,

J2.4, 2.6 Hz, H-3), 4.00±3.92 (2H, m, H-6, H-5), 3.82

(1H, dd, J5.9, 11.4 Hz, H-7a), 3.71 (1H, dd, J4.4,

11.4 Hz, H-7b), 3.58 (1H, dd, J2.4, 9.7 Hz, H-4), 3.51

(3H, s, OCH₃), 3.19 (1H, dd, J2.6, 7.9 Hz, H-2). ¹³C

NMR (50 MHz, CDCl₃) d: 138.8, 138.4, 137.6 and

128.4±127.4 (Ph), 102.1 (C-1), 78.6, 75.2, 74.7, 73.6 and

69.1 (C-2,3,4,5,6), 74.5, 72.9, 71.8 and 65.2 (C-7, 3CH₂Ph),

57.1 (OCH₃). HR MS (LSIMS): C₂₉H₃₄O₇1Na¹[M1Na]¹;

Calcd: 517.22022. Found: 517.22081.

Methylation of 50 was carried out in similar manner as

benzylation using MeI instead of BnBr to afford a

compound (84%) displaying the same optical rotation, IR

and NMR spectra as 48.

Methyl 7-O-allyl-2,3,4,6-tetra-O-benzyl-l-glycero-b-d-

allo-heptopyranoside (49). Benzylation of 22 to 49 was

carried out in the same way as benzylation of 18. Colourless

oil; yield 82%, [a]_D110.1 (c 1.1, CHCl₃); ¹H NMR

(200 MHz, CDCl₃) d: 7.40±7.15 (20H, m, 4Ph), 6.00±

5.80 (1H, m, OCH₂CHCH₂), 5.33±5.12 (2H, m,

OCH₂CHCH₂), 4.92±4.15 (4£2H, 4ABq, 4CH₂Ph), 4.77

(1H, d, J7.9 Hz, H-1), 4.18 (1H, dd, J2.5, 2.6 Hz,

H-3), 4.10±3.97 (4H, m, H-5, H-6, OCH₂CHCH₂), 3.81±

3.65 (2H, m, H-7a, H-7b), 3.67 (1H, dd, J2.5, 9.7 Hz,

H-4), 3.52 (3H, s, OCH₃), 3.28 (1H, dd, J2.6, 7.9 Hz,

H-2). ¹³C NMR (50 MHz, CDCl₃) d: 139.0, 138.8, 138.8

and 138.0 (Ph), 134.7 (OCH₂CHCH₂), 128.2±127.3 (Ph),

116.8 (OCH₂CHCH₂), 102.2 (C-1), 79.0, 75.7, 75.6, 74.6

and 72.5 (C-2,3,4,5,6), 74.4, 73.2, 72.9, 72.3, 70.8 and

70.7 (C-7, 4CH₂Ph, OCH₂CHCH₂), 56.6 (OCH₃). HR MS

(LSIMS): C₃₉H₄₄O₇1Na¹[M1Na]¹; Calcd: 647.29847.

Found: 647.29817.

Desilylation of 24

To a solution of 24 (600 mg, 0.98 mmol) in CH₃COOH

(8 ml) were added KBr (139 mg, 1.17 mmol) and

CH₃COONa (1 g). The mixture was cooled to 08C and stir-

red with exclusion of light. CH₃CO₃H (5 ml, 30% solution

in acetic acid) was added to the mixture. After stirring for

2 h at 08C mixture was brought to room temperature. Aq

15% Na₂S₂O₅was added to reduce the remaining peroxy-

acetic acid. The product was extracted with CH₂Cl₂and the

organic extract was washed with water, aq 10% NaHCO₃

and water again, dried and concentrated. The residue was

puri®ed on a silica gel column with 1:2 hexane±EtOAc to

yield 6,7-diol (377 mg, 78%) identical after IR and NMR

spectra with 51.

Methyl 2,3,4,6-tetra-O-benzyl-l-glycero-b-d-allo-hepto-

pyranoside (50). Obtained by de-allylation of 49 in 70%.

De-allylation protocol is described below for 22 (affording

51). Colourless oil; [a]_D118.1 (c 1.3, CHCl₃); n_max(®lm)

3493 (br), 3064, 3031, 2888, 1497, 1454, 1350, 1207, 1132,

Methyl 2,3,4,6,7-penta-O-benzyl-l-glycero-b-d-allo-hepto-

pyranoside (52). Benzylation of 14 and 51 leading to 52

was carried out as for 18. Both benzylation products (83 and

81%, respectively) displayed identical IR and NMR spectra.

Colourless oil; [a]_D111.7 (c 1.2, CHCl₃); n_max(®lm)

3064, 3031, 2908, 1497, 1454, 1351, 1206, 1095, 1028,

1

1093, 1048, 737, 698 cm²¹; H NMR (200 MHz, CDCl₃)

d: 7.42±7.15 (20H, m, 4Ph), 4.95±4.23 (4£2H,

4ABq,4CH₂Ph), 4.84 (1H, d, J7.9 Hz, H-1), 4.19 (1H,

dd, J2.4, 2.5 Hz, H-3), 4.11 (1H, dd, J1.5, 9.6 Hz,

H-5), 4.03±3.80 (3H, m, H-6, H-7a, H-7b), 3.70 (1H, dd,

;

912, 737, 698 cm²^{1 1}H NMR (200 MHz, CDCl₃) d:

7.42±7.15 (25H, m, 5Ph), 4.92±4.15 (5£2H, 5ABq,

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

9333

5CH₂Ph), 4.75 (1H, d, J8.0 Hz, H-1), 4.20±4.15 (1H, m,

H-3), 4.13±4.03 (2H, m, H-5, H-6), 3.81 (1H, dd, J5.8,

9.9 Hz, H-7a), 3.76 (1H, dd, J5.9, 9.9 Hz, H-7b), 3.67 (1H,

dd, J2.4, 9.5 Hz, H-4), 3.46 (3H, s, OCH₃), 3.27 (1H, dd,

J2.6, 8.0 Hz, H-2). ¹³C NMR (50 MHz, CDCl₃) d: 139.0,

138.7, 138,7, 138.2, 137.9 and 128.3±127.3 (Ph), 102.2

(C-1), 78.9, 75.7, 75.6, 74.5 and 72.4 (C-2,3,4,5,6), 74.4,

73.4, 73.2, 72.9, 70.9 and 70.7 (C-7, 5CH₂Ph), 56.6 (OCH₃).

HR MS (LSIMS): C₄₃H₄₆O₇1Na¹[M1Na]¹; Calcd:

697.31412. Found: 697.31737.

(carried out as de-allylation of 22). Colourless needles,

mp 88±898C (from hexane±ethanol); [a]_D140.3 (c 1.0,

CHCl₃); ¹H NMR (200 MHz, CDCl₃) d: 7.40±7.15 (20H, m,

4Ph), 5.50±4.36 (4£2H, 4ABq, 4CH₂Ph), 4.63 (1H, d,

J3.6 Hz, H-1), 4.02 (1H, dd, J8.4, 9.6 Hz, H-3), 4.00±

3.72 (5H, m, H-4, H-5, H-6, H-7a, H-7b), 3.58 (1H, dd,

J3.6, 9.6 Hz, H-2), 3.40 (3H, s, OCH₃). ¹³C NMR

(50 MHz, CDCl₃) d: 138.5, 138.3, 138.0, 137.8 and

128.4±127.4 (Ph), 98.3 (C-1), 82.3, 79.6, 77.2, 75.1 and

72.4, (C-2,3,4,5,6), 75.8, 74.6, 73.5, 72.0 and 62.5 (C-7,

4CH₂Ph), 55.4 (OCH₃). HR MS (LSIMS): C₃₆H₄₀O₇1Na¹

[M1Na]¹; Calcd: 607.26715. Found: 607.27034. Anal.

Calcd for C₃₆H₄₀O₇: C, 73.95; H, 6.90. Found: C, 73.76;

H, 7.00.

d-glycero-ab-d-allo-heptose (53). To a cooled (108C) solu-

tion of 13 (104 mg, 0.18 mmol) in EtOAc (1.11 ml) was

added a solution of H₂SO₄in Ac₂O (1:300 v/v, 2.23 ml)

and was stirred 50 min (TLC) at room temperature. Then

an excess of NaHCO₃was added to neutralize the reaction

mixture, NaHCO₃was ®ltered off and washed with toluene

twice. The combined organic layers were evaporated to

dryness. The crude product was dissolved in MeOH

(1 ml), and 0.1N MeONa in MeOH (0.01 ml) was added.

The mixture was stirred 30 min and then neutralized with

Amberlite IR 120 (H¹) ion exchange resin. After ®ltration,

the resin was washed several times with aq methanol, and

®ltrate was evaporated to dryness under lowered pressure.

The residue was chromatographed with 1:2 hexane±EtOAc.

The dry product was dissolved in MeOH (3 ml) and 10%

Pd±C catalyst (100 mg) was added. Suspension was hydro-

genated (Pd/C) overnight. Filtration through a Celite pad

and concentration of the ®ltrate left a foam which was

washed by decantation with ether, then the rest of ether

was evaporated to dryness giving 53 as a foam. Yield

20 mg, 79%, [a]_D110.7 (24 h) (c 1.6, H₂O). Lit.²⁷:

[a]_D17.2 (3 min)!112.7 (24 h) (c 4.6, H₂O). ¹³C

NMR (50 MHz, D₂O) d: major: 93.8 (C-1), 73.8, 72.1,

71.3, 71.2, 67.7, 61.8; minor: 92.7 (C-1), 72.0, 71.7, 67.6,

67.1, 66.9, 62.1. These data are identical with the literature²⁸

values for b- and a-pyranose forms.

Methyl 2,3,4,6-tetra-O-benzyl-7-O-methyl-l-glycero-a-

d-gluco-heptopyranoside (57). Obtained (94%):by methyl-

ation of 56 (carried out as methylation of 50). Colourless oil;

[a]_D138.4 (c 4.9, CHCl₃); n_max(®lm) 3064, 3031, 2924,

1497, 1454, 1360, 1196, 1158, 1141, 1095, 1069, 1030, 739,

698 cm²¹; ¹H NMR (200 MHz, CDCl₃) d: 7.42±7.18 (20H,

m, 4Ph), 5.04±4.30 (4£2H, 4ABq, 4CH₂Ph), 4.64 (1H, d,

J3.6 Hz, H-1), 4.09±3.98 (2H, m, H-3, H-6), 3.85±3.55

(4H, m, H-4, H-5, H-7a, H-7b), 3.58 (1H, dd, J3.6, 9.6 Hz,

H-2), 3.37, 3.36 (2£3H, 2s, 2OCH₃). ¹³C NMR (50 MHz,

CDCl₃) d: 138.5, 138.5, 138.0, 138.0 and 128.4±127.3 (Ph),

98.1 (C-1), 82.5, 79.8, 77.2, 74.5 and 69.9 (C-2,3,4,5,6),

75.8, 74.5, 73.4, 72.9 and 72.4 (C-7, 4CH₂Ph), 58.9 and

55.0 (2OCH₃). HR MS (LSIMS): C₃₇H₄₂O₇1Na¹

[M1Na]¹; Calcd: 621.28284. Found: 621.28135.

Benzylation of 28 (carried out as benzylation of 18) gave a

compound (78.9%) with the same optical rotation, and

identical IR and NMR spectra as 57.

Methyl

2,3,4,6,7-penta-O-benzyl-l-glycero-a-d-gluco-

heptopyranoside (58). Benzylation of 56 was carried out

as benzylation of 18. Colourless oil; yield 87%,

1

The same protocol was used for deprotection of 14.

l-glycero-d-allo-heptose (54) obtained was characterized

only by optical rotation [a]_D18.9 (c 1.77, H₂O), and ¹³C

NMR data of the major component [b-pyranose (?)] (50 MHz,

D₂O) d 93.7 (C-1), 72.2, 71.4, 71.3, 69.0, 66.2, 62.8.

[a]_D127.1 (c 3.8, CHCl₃); H NMR (200 MHz, CDCl₃)

d: 7.42±7.20 (25H, m, 5Ph), 5.05±4.31 (5£2H, 5ABq,

5CH₂Ph), 4.63 (1H, d, J3.6 Hz, H-1), 4.15±4.06 (1H, m,

H-6), 4.04 (1H, dd, J8.6, 9.5 Hz, H-3), 3.89±3.67 (4H, m,

H-4, H-5, H-7a, H-7b), 3.58 (1H, dd, J3.6, 9.6 Hz, H-2),

3.32 (3H, s, OCH₃). ¹³C NMR (50 MHz, CDCl₃) d: 138.5,

138.5, 138.1, 138.1, 137.9 and 128.4±127.3 (Ph), 98.1

(C-1), 82.5, 79.8, 77.2, 74.8 and 70.0 (C-2,3,4,5,6), 75.8,

74.5, 73.4, 73.4, 73.0 and 70.2 (C-7, 5CH₂Ph), 55.1 (OCH₃).

HR MS (LSIMS): C₄₃H₄₆O₇1Na¹[M1Na]¹; Calcd:

697.31415. Found: 697.31273.

Methyl 7-O-allyl-2,3,4,6-tetra-O-benzyl-l-glycero-a-d-

gluco-heptopyranoside (55). Obtained by benzylation of

30 (carried out in the same manner as benzylation of 18).

1

Colourless oil; yield 86%, [a]_D136.8 (c 1.1, CHCl₃); H

NMR (200 MHz, CDCl₃) d: 7.40±7.17 (20H, m, 4Ph),

6.00±5.80 (1H, m, OCH₂CHCH₂), 5.34±5.14 (2H, m,

OCH₂CHCH₂), 5.04±4.31 (4£2H, 4ABq, 4CH₂Ph), 4.63

(1H, d, J3.6 Hz, H-1), 4.11±3.96 (4H, m, H-3, H-6,

OCH₂CHCH₂), 3.87±3.54 (5H, m, H-2, H-4, H-5, H-7a,

H-7b), 3.36 (3H, s, OCH₃). ¹³C NMR (125 MHz, CDCl₃)

d: 138.5, 138.5, 138.5 and 138.1 (Ph), 134.4

(OCH₂CHCH₂), 128.4±127.3 (Ph), 117.0 (OCH₂CHCH₂),

98.1 (C-1), 82.5, 79.8, 77.2, 74.7 and 69.9 (C-2,3,4,5,6),

75.8, 74.5, 73.4, 73.0, 72.3 and 69.9 (C-7, 4CH₂Ph,

OCH₂CHCH₂), 55.1 (OCH₃). Anal. Calcd for C₃₉H₄₄O₇:

C, 74.98; H, 7.10. Found: C, 74.77; H, 7.06.

Benzylation of 26 (carried out as benzylation of 18) gave a

compound (89.6%) with the same optical rotation and

identical NMR spectra as 58.

Methyl

2,3,4-tri-O-benzyl-l-glycero-a-d-gluco-hepto-

pyranoside (59). De-allylation of 30 (carried out as de-

allylation of 22) gave 59 (77%): Colourless needles, mp

105±1068C (from hexane±methanol); [a]_D118.2 (c 1.0,

CHCl₃); n_max(KBr) 3354 (br), 3062, 3031, 2921, 1498,

1

1455, 1360, 1163, 1095, 1052, 1025, 732, 695 cm²¹; H

NMR (200 MHz, CDCl₃) d: 7.42±7.24 (15H, m, 3Ph),

5.04±4.61 (3£2H, 3ABq, 3CH₂Ph), 4.55 (1H, d,

J3.6 Hz, H-1), 4.05±3.88 (2H, m, H-3, H-6), 3.82±3.60

Methyl 2,3,4,6-tetra-O-benzyl-l-glycero-a-d-gluco-hepto-

pyranoside (56). Obtained (83%) by de-allylation of 55

9334

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

(4H, m, H-4, H-5, H-7a, H-7b), 3.50 (1H, dd, J3.6, 9.7 Hz,

H-2), 3.34 (3H, s, OCH₃). ¹³C NMR (50 MHz, CDCl₃) d:

138.6, 138.0, 138.0 and 128.5±127.6 (Ph), 98.4 (C-1), 81.9,

79.6, 77.1, 71.3 and 68.8 (C-2,3,4,5,6), 75.7, 75.1, 73.5 and

64.9 (C-7, 3CH₂Ph), 55.2 (OCH₃). Anal. Calcd for

C₂₉H₃₄O₇: C, 70.43; H, 6.93. Found: C, 70.27; H, 6.91.

pyranoside (64). De-allylation of 63 (carried out as de-

allylation of 22) gave 64 (77%). Colourless oil;

[a]_D14.4 (c 1.96, CHCl₃); n_max(®lm) 3493 (br), 3031,

2923, 1497, 1454, 1350, 1197, 1138, 1102, 1057, 784, 737,

698 cm²¹; ¹H NMR (200 MHz, CDCl₃) d: 7.45±7.20 (20H,

m, 4Ph), 5.14±4.22 (4£2H, 4ABq, 4CH₂Ph), 4.69 (1H, d,

J3.3 Hz, H-1), 4.14±4.10 (1H,m, H-4), 4.07 (1H, dd,

J3.3, 10.1 Hz, H-2), 3.98 (1H, dd, J2.2, 10.1 Hz, H-3),

3.90±3.68 (4H, m, H-5, H-6, H-7a, H-7b), 3.40 (3H, s,

OCH₃). ¹³C NMR (50 MHz, CDCl₃) d: 138.8, 138.8,

138.4, 137.8 and 128.5±127.4 (Ph), 98.8 (C-1), 79.5, 76.7,

76.2, 74.9 and 69.1 (C-2,3,4,5,6), 74.5, 73.5, 73.4, 71.7 and

60.2 (C-7, 4CH₂Ph), 55.3 (OCH₃). HR MS (LSIMS):

C₃₆H₄₀O₇1Na¹[M1Na]¹; Calcd: 607.26717. Found:

607.26805.

Oxidative removal of the phenyldimethylsilyl group in 31

was carried out in the same manner as in the case of 24 to

give a compound (78.2%) having the same melting point,

the same optical rotation and identical IR and NMR spectra

as 59.

Methyl 6,7-di-O-acetyl-2,3,4-tetra-O-benzyl-7-O-methyl-

l-glycero-a-d-gluco-heptopyranoside (60). Acetylation of

59 under standard condition gave 60 (90%). Colourless oil;

[a]_D29.9 (c 2.3, CHCl₃); lit.^29,30: [a]_D210.6 (c 1.1,

CHCl₃).

Methyl 2,3,4,6-tetra-O-benzyl-7-O-methyl-d-glycero-a-

d-galacto-heptopyranoside (65). Methylation of 64

(carried out as methylation of 50) gave 65 (90%). Colourless

oil; [a]_D112.7 (c 1.73, CHCl₃); n_max(®lm) 3031, 2922,

1497, 1454, 1349, 1195, 1103, 1060, 1028, 784, 737,

Methyl

2,3,4-tri-O-benzyl-d-glycero-a-d-gluco-hepto-

pyranoside (61). De-allylation of 29 (carried out as de-

allylation of 22) gave 61 (61%). Amorphous solid;

698 cm²^{1 1}H NMR (200 MHz, CDCl₃) d: 7.43±7.21

;

1

[a]_D134.2 (c 2.4, CHCl₃); H NMR (200 MHz, CDCl₃)

(20H, m, 4Ph), 5.09±4.28 (4£2H, 4ABq, 4CH₂Ph), 4.67

(1H, d, J3.4 Hz, H-1), 4.19±4.15 (1H,m, H-4), 4.06 (1H,

dd, J3.4, 10.1 Hz, H-2), 3.96 (1H, dd, J2.6, 10.1 Hz,

H-3), 3.89 (1H, dd, J,1, 9.5 Hz, H-5), 3.80 (1H, ddd,

J1.8, 3.2, 9.5 Hz, H-6), 3.70 (1H, dd, J1.8, 10.6 Hz,

H-7a), 3.55 (1H, dd, J3.2, 10.6 Hz, H-7b), 3.36, 3.34

(2£3H, 2s, 2OCH₃). ¹³C NMR (50 MHz, CDCl₃) d: 139.0,

138.8, 138.5, 138.3 and 128.3±127.3 (Ph), 98.8 (C-1), 79.5,

76.3, 75.9, 75.0 and 68.3 (C-2,3,4,5,6), 74.6, 73.5, 73.3, 71.7

and 70.5 (C-7, 4CH₂Ph), 59.1 and 55.0 (2OCH₃). HR MS

(LSIMS): C₃₇H₄₂O₇1Na¹[M1Na]¹; Calcd: 621.28282.

Found: 621.28401.

d: 7.40±7.20 (15H, m, 3Ph), 5.08±4.61 (3£2H, 3ABq,

3CH₂Ph), 4.54 (1H, d, J3.7 Hz, H-1), 4.03 (1H, dd,

J9.0, 9.3 Hz, H-3), 3.84±3.46 (6H, m, H-2, H-4, H-5,

H-6, H-7a, H-7b), 3.39 (3H, s, OCH₃). ¹³C NMR

(50 MHz, CDCl₃) d: 138.4, 137.9, 137.3 and 128.6±127.7

(Ph), 97.7 (C-1), 82.2, 80.0, 79.8, 72.5 and 69.7

(C-2,3,4,5,6), 75.7, 74.9, 73.3 and 62.8 (C-7, 3CH₂Ph),

55.4 (OCH₃). HR MS (LSIMS): C₂₉H₃₄O₇1Na¹

[M1Na]¹; Calcd: 517.22022. Found: 517.22034. Anal.

Calcd for C₂₉H₃₄O₇: C, 70.43; H, 6.93. Found: C, 70.18;

H, 6.91.

Methyl 6,7-di-O-acetyl-2,3,4-tetra-O-benzyl-7-O-methyl-

d-glycero-a-d-gluco-heptopyranoside (62). Acetylation of

61 under standard condition gave 62 (92%). Colourless oil;

[a]_D123.5 (c 1.8, CHCl₃); lit.^29,30: [a]_D121.8 (c 0.9,

CHCl₃).

Benzylation of 34 (carried out as benzylation of 18) afforded

(81%) a compound identical (optical rotation, IR and NMR

spectra) with 65.

Methyl 2,3,4-tri-O-benzyl-d-glycero-a-d-galacto-hepto-

pyranoside (66). De-allylation of 36 (carried out as de-

allylation of 22) gave 66 (90%). Colourless oil;

[a]_D113.6 (c 1.22, CHCl₃); n_max(®lm) 3446 (br), 3031,

2928, 1497, 1455, 1352, 1195, 1147, 1101, 1049, 901, 783,

Methyl 7-O-allyl-2,3,4,6-tetra-O-benzyl-d-glycero-a-d-

galacto-heptopyranoside (63). Benzylation of 36 (carried

out as benzylation of 18) gave 63 (85%). Colourless oil;

[a]_D116.7 (c 1.1, CHCl₃); n_max(®lm) 3064, 3031,

2907, 2865, 1497, 1454, 1350, 1196, 1103, 1059, 1028,

1

738, 697 cm²¹; H NMR (200 MHz, CDCl₃) d: 7.45±7.22

(15H, m, 3Ph), 5.05±4.65 (3£2H, 3ABq, 3CH₂Ph), 4.65

(1H, d, J3.6 Hz, H-1), 4.10±4.06 (1H, m, H-4), 4.05

(1H, dd, J3.6, 10.1 Hz, H-2), 3.94 (1H, dd, J2.8,

10.1 Hz, H-3), 3.80±3.52 (4H, m, H-5, H-6, H-7a, H-7b),

3.33 (3H, s, OCH₃). ¹³C NMR (50 MHz, CDCl₃) d: 138.7,

138.5, 138.4 and 128.7±127.5 (Ph), 98.8 (C-1), 79.2, 76.4,

73.4, 69.8 and 69.2 (C-2,3,4,5,6), 74.3, 73.6, 73.5 and 63.9

(C-7, 3CH₂Ph), 55.3 (OCH₃). HR MS (LSIMS):

C₂₉H₃₄O₇1Na¹[M1Na]¹; Calcd: 517.22022. Found:

517.22085.

1

929, 784, 737, 698 cm²¹; H NMR (200 MHz, CDCl₃) d:

7.42±7.20 (20H, m, 4Ph), 6.00±5.79 (1H, m,

OCH₂CHCH₂), 5.32±5.12 (2H, m, OCH₂CHCH₂), 5.11±

4.30 (4£2H, 4ABq, 4CH₂Ph), 4.68 (1H, d, J3.4 Hz,

H-1), 4.21±4.17 (1H, m, H-4), 4.06 (1H, dd, J3.4,

10.0 Hz, H-2), 4.02±3.92 (3H, m, H-3, OCH₂CHCH₂),

3.90±3.83 (2H, m, H-5, H-6), 3.78 (1H, dd, J1.4,

10.6 Hz, H-7a), 3.59 (1H, dd, J3.4, 10.6 Hz, H-7b), 3.37

(3H, s, OCH₃). ¹³C NMR (50 MHz, CDCl₃) d: 139.0, 138.9,

138.5 and 138.4 (Ph), 134.7 (OCH₂CHCH₂), 128.3±127.3

(Ph), 116.9 (OCH₂CHCH₂), 98.8 (C-1), 79.6, 76.3, 76.0,

75.0 and 68.5 (C-2,3,4,5,6), 74.5, 73.5, 73.3, 72.3, 71.8

and 68.3 (C-7, 4CH₂Ph, OCH₂CHCH₂), 55.2 (OCH₃). HR

MS (LSIMS): C₃₉H₄₄O₇1Na¹[M1Na]¹; Calcd:

647.29847. Found: 647.29792.

Methyl d-glycero-a-d-galacto-heptopyranoside (67). To a

solution of 66 (300 mg, 0.51 mmol) in EtOH (5 ml) was

added 10% Pd±C (300 mg), and the suspension was hydro-

genated overnight. Filtration through a Celite pad and

concentration of the ®ltrate left a foam which was washed

by decantation with ether, then the rest of ether was evapo-

rate and the product was recrystallized from ethanol as

Methyl 2,3,4,6-tetra-O-benzyl-d-glycero-a-d-galacto-hepto-

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

9335

colourless solid. Yield 84 mg, 85%, mp 140±1428C,

[a]_D1158.9 (c 1.1, H₂O). Lit.⁷: [a]_D1165 (c 0.9,

H₂O). The ¹³C NMR data of 67 (in D₂O) are the same as

in literature.⁷

(2£(CH₃)₂C). HR MS (LSIMS): C₂₃H₃₀O₈1Na¹

[M1Na]¹; Calcd: 457.18384. Found: 457.18425.

7-O-Allyl-6-O-benzoyl-1,2:3,4-di-O-isopropylidene-l-

glycero-a-d-galacto-heptopyranose (71). Amorphous

1

Hydrogenation of 32 was carried out in the same manner to

give a compound (89.3%) having identical data (melting

point, optical rotation and the NMR spectra) as 67.

solid; [a]_D248.9 (c 1.6, CHCl₃); H NMR (200 MHz,

CDCl₃) d: 8.11±7.35 (Ph), 5.98±5.77 (1H, m,

OCH₂CHCH₂), 5.53 (1H, d, J5.0 Hz, H-1), 5.43 (1H,

ddd, J3.1, 3.7, 7.7 Hz, H-6), 5.32±5.08 (2H, m,

OCH₂CHCH₂), 4.64 (1H, dd, J2.5, 7.9 Hz, H-3), 4.37

(1H, dd, J1.8, 7.9 Hz, H-4), 4.33 (1H, dd, J2.5,

5.0 Hz, H-2), 4.27 (1H, dd, J1.8, 7.7 Hz, H-5), 4.15±

3.92 (2H, m, OCH₂CHCH₂), 3.90 (1H, dd, J3.7,

11.4 Hz, H-7a), 3.80 (1H, dd, J3.1, 11.4 Hz, H-7b),

1.60, 1.42, 1.34, 1.32 (4£3H, 4s, 2 (CH₃)₂C). ¹³C NMR

(50 MHz, CDCl₃) d: 166.2 (CvO), 134.4, 132.7, 130.5,

129.7 and 128.2 (Ph, OCH₂CHvCH₂), 116.8

(OCH₂CHvCH₂), 109.6 and 108.7 (2£(CH₃)₂C), 96.4

(C-1), 73.3, 71.2, 71.0, 70.6 and 67.0 (C-2,3,4,5,6), 72.3

(OCH₂CHvCH₂), 68.5 (C-7), 26.0, 26.0, 25.1 and 24.5

(2£(CH₃)₂C). HR MS (LSIMS): C₂₃H₃₀O₈1Na¹

[M1Na]¹; Calcd: 457.18384. Found: 457.18429.

Methyl l-glycero-a-d-galacto-heptopyranoside (68).

Hydrogenation of 33 (carried out as hydrogenation of 66)

gave 68 (87%). Yield 80.2%, colourless solid, mp 129±

1308C (from ethanol); [a]_D1154.6 (c 1.0, H₂O); ¹³C

NMR (50 MHz, D₂O) d: 99.4 (C-1), 71.3, 70.5, 69.6, 69.4

and 68.1 (C-2,3,4,5,6), 61.9 (C-7), 55.1 (OCH₃). HR MS

(LSIMS): C₈H₁₆O₇1Na¹[M1Na]¹; Calcd: 247.07937.

Found: 247.07919.

Hydrogenation of 69 (carried out as hydrogenation of 66)

gave a compound (80%) identical (melting point, optical

rotation and NMR spectra) with 68.

Methyl 2,3,4-tri-O-benzyl-l-glycero-a-d-galacto-hepto-

pyranoside (69). Oxidative removal of phenyldimethylsilyl

group in 39 (carried out as for 24) led to 69 (84%). Colour-

less oil; [a]_D116.6 (c 1.7, CHCl₃); n_max(®lm) 3468 (br),

3031, 2908, 1497, 1454, 1351, 1196, 1132, 1095, 1048, 782,

1,2:3,4-Di-O-isopropylidene-d-glycero-a-d-galacto-hepto-

pyranose (72). De-allylation of 44 (carried out as de-allyl-

ation of 22) gave 72 (89%). Colourless oil; [a]_D248.5 (c

1.1, CHCl₃); lit.³¹: [a]_D251.7 (c 2.1, CHCl₃); n_max(®lm)

3445 (br), 2988, 2938, 1458, 1382, 1256, 1213, 1170, 1068,

1

738, 698 cm²¹; H NMR (200 MHz, CDCl₃) d: 7.46±7.24

1

(15H, m, 3Ph), 5.12±4.62 (3£2H, 3ABq, 3CH₂Ph), 4.74

(1H, d, J3.5 Hz, H-1), 4.08 (1H, dd, J3.5, 10.6 Hz,

H-2), 4.01±3.95 (1H,m, H-4), 3.96 (1H, dd, J2.3,

10.6 Hz, H-3), 3.92±3.82 (1H, m, H-6), 3.73 (1H, dd,

J,1, 5.7 Hz, H-5), 3.49 (1H, dd, J3.8, 11.5 Hz, H-7a),

3.37 (3H, s, OCH₃), 3.34 (1H, dd, J5.0, 11.5 Hz, H-7b).

¹³C NMR (50 MHz, CDCl₃) d: 138.5, 138.2, 137.7 and

128.5±127.5 (Ph), 98.7 (C-1), 79.2, 76.2, 76.1, 71.5 and

69.2 (C-2,3,4,5,6), 74.5, 73.8, 73.6 and 62.8 (C-7,

3CH₂Ph), 55.4 (OCH₃). HR MS (LSIMS): C₂₉H₃₄O₇1Na¹

[M1Na]¹; Calcd: 517.22022. Found: 517.22006.

1001, 899, 776 cm²¹; H NMR (200 MHz, CDCl₃) d: 5.52

(1H, d, J5.1 Hz, H-1), 4.65 (1H, dd, J2.4, 7.9 Hz, H-3),

4.45 (1H, dd, J1.7, 7.9 Hz, H-4), 4.33 (1H, dd, J2.4,

5.1 Hz, H-2), 4.00±3.70 (4H, m, H-5, H-6, H-7a, H-7b),

1.53, 1.46, 1.37, 1.33 (4£3H, 4s, 2£(CH₃)₂C). ¹³C NMR

(50 MHz, CDCl₃) d: 109.4 and 108.8 (2£(CH₃)₂C), 96.3

(C-1), 70.9, 70.7, 70.6, 70.3 and 67.4 (C-2,3,4,5,6), 63.9

(C-7), 25.9, 25.9, 25.0 and 24.4 (2£(CH₃)₂C). HR MS

(LSIMS): C₁₃H₂₂O₇1Na¹[M1Na]¹; Calcd: 313.12632.

Found: 313.12677.

Oxidative removal of phenyldimethylsilyl group in 46

(carried out as for 24) afforded a compound (78%) with

the same optical rotation and the same IR and NMR spectra

as 72.

The mixture of 44 and 45 was benzoylated under standard

condition to give a mixture of 6-O-benzoyl derivatives

(overall yield 92%), which was separated by HPLC (eluent:

hexane±ethyl acetate 6:1) to afford 70 (71%) and 71

(17%).

Hydrogenation of 40 (carried out as hydrogenation of 66)

gave a compound (83%) having the same optical rotation

and NMR spectra as 72.

7-O-Allyl-6-O-benzoyl-1,2:3,4-di-O-isopropylidene-d-

glycero-a-d-galacto-heptopyranose (70). Colourless oil;

[a]_D247.5 (c 2.2, CHCl₃); n_max(®lm) 2988, 2937, 1724

(CvO), 1383, 1272, 1213, 1169, 1071, 1005, 898,

713 cm²¹; ¹H NMR (200 MHz, CDCl₃) d: 8.11±7.40 (Ph),

5.97±5.76 (1H, m, OCH₂CHCH₂), 5.54 (1H, d, J5.0 Hz,

H-1), 5.30 (1H, ddd, J2.3, 3.6, 8.9 Hz, H-6), 5.29±5.06

(2H, m, OCH₂CHCH₂), 4.64 (1H, dd, J2.4, 7.9 Hz, H-3),

4.42±4.31 (2H, m, H-4, H-5), 4.33 (1H, dd, J2.4, 5.0 Hz,

H-2), 4.05±3.99 (2H, m, OCH₂CHCH₂), 3.89 (1H, dd,

J2.3, 11.3 Hz, H-7a), 3.80 (1H, dd, J3.6, 11.3 Hz,

H-7b), 1.57, 1.43, 1.35, 1.25 (4£3H, 4s, 2£(CH₃)₂C). ¹³C

NMR (50 MHz, CDCl₃) d: 165.5 (CvO), 134.9, 132.9,

130.3, 129.7 and 128.3 (Ph, OCH₂CHCH₂), 116.7

(OCH₂CHCH₂), 109.4 and 109.0 (2£(CH₃)₂C), 96.3 (C-1),

72.4 (OCH₂CHCH₂), 71.9, 70.9, 70.6, 70.6 and 65.4

(C-2,3,4,5,6), 67.7 (C-7), 26.1, 25.9, 25.1 and 24.4

7-O-Allyl-6-O-benzyl-1,2:3,4-di-O-isopropylidene-d-

glycero-a-d-galacto-heptopyranose (73). Benzylation of

44 (carried out as benzylation of 18) gave 73 (82%). Colour-

less oil; [a]_D253.8 (c 1.3, CHCl₃); n_max(®lm) 2988,

2903, 1455, 1382, 1256, 1213, 1108, 1069, 1003, 921,

899, 747, 699 cm²^{1 1}H NMR (200 MHz, CDCl₃) d:

;

7.43±7.22 (5H, m, Ph), 6.05±5.83 (1H, m,

OCH₂CHvCH₂), 5.49 (1H, d, J4.9 Hz, H-1), 5.35±5.10

(2H, m, OCH₂CHvCH₂), 4.79 (1H, d, J11.2 Hz,

CHHPh), 4.64 (1H, d, J11.2 Hz, CHHPh), 4.61 (1H, dd,

J2.2, 8.0 Hz, H-3), 4.49 (1H, dd, J1.7, 8.0 Hz, H-4), 4.27

(1H, dd, J2.2, 4.9 Hz, H-2), 4.07±4.02 (2H, m,

OCH₂CHCH₂), 3.93 (1H, dd, J1.7, 9.3 Hz, H-5), 3.81±

3.72 (2H, m, H-6, H-7a), 3.57 (1H, dd, J5.1, 10.8 Hz,

H-7b), 1.50, 1.45, 1.37, 1.31 (4£3H, 4s, 2£(CH₃)₂C). ¹³C

9336

M. Kim et al. / Tetrahedron 56 (2000) 9319±9337

NMR (50 MHz, CDCl₃) d: 138.6 (Ph), 135.1

(OCH₂CHvCH₂), 128.2, 128.1 and 127.5 (Ph), 116.5

(OCH₂CHvCH₂), 108.8 and 108.6 (2£(CH₃)₂C), 96.3

(C-1), 76.7, 71.0, 70.6, 70.4 and 66.1 (C-2,3,4,5,6), 73.2,

72.5 and 69.7 (C-7, OCH₂CHvCH₂, CH₂Ph), 26.1, 26.1,

25.1 and 24.4 (2£(CH₃)₂C). HR MS (LSIMS):

C₂₃H₃₂O₇1Na¹[M1Na]¹; Calcd: 443.20457. Found:

443.20380.

MS (LSIMS): C₁₃H₂₂O₇1Na¹[M1Na]¹; Calcd:

313.12632. Found: 313.12775. Anal. Calcd for C₁₃H₂₂O₇:

C, 53.58; H, 7.64. Found: C, 53.75; H, 7.79.

Acknowledgements

This work was ®nanced from the Grant No. 3 TO9A 066 12

obtained from the Polish State Committee for Scienti®c

Research (KBN). The authors are grateful to Dr Zo®a

Urbanczyk-Lipkowska for X-ray structural determination

of compounds 18 and 28.

6-O-Benzyl-1,2:3,4-di-O-isopropylidene-d-glycero-a-d-

galacto-heptopyranose (74). De-allylation of 73 (carried

out as de-allylation of 22) gave 74 (85%). Colourless oil;

1

[a]_D255.5 (c 1.7, CHCl₃); H NMR (200 MHz, CDCl₃)

d: 7.40±7.25 (5H, m, Ph), 5.50 (1H, d, J4.9 Hz, H-1), 4.67

(2H, s, CH₂Ph), 4.62 (1H, dd, J2.4, 8.1 Hz, H-3), 4.45 (1H,

dd, J1.7, 8.1 Hz, H-4), 4.30 (1H, dd, J2.4, 4.9 Hz, H-2),

4.01±3.68 (4H, m, H-5, H-6, H-7a, H-7b), 1.53, 1.46, 1.37,

1.32 (4£3H, 4s, 2£(CH₃)₂C). ¹³C NMR (50 MHz, CDCl₃) d:

138.3, 128.3, 128.0 and 127.8 (Ph), 109.0 and 108.8

(2£(CH₃)₂C), 96.3 (C-1), 77.1, 70.9, 70.6, 70.4 and 66.7

(C-2,3,4,5,6), 72.8 and 61.7 (C-7, CH₂Ph), 26.0, 26.0, 25.0

and 24.4 (2£(CH₃)₂C). HR MS (LSIMS): C₂₀H₂₈O₇1Na¹

[M1Na]¹; Calcd: 403.17327. Found: 403.17518.

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Article Doi

Homologation of protected hexoses with Grignard C1 reagents

DOI: 10.1016/S0040-4020(00)00847-4

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