Synthesis and NMR characterization of the six regioisomeric monophosphates of octyl β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-β-D- glucopyranoside

Carbohydrate Research 337 (2002) 2127–2151

www.elsevier.com/locate/carres

Synthesis and NMR characterization of the six regioisomeric

monophosphates of octyl b- -galactopyranosyl-

(14)-2-acetamido-2-deoxy-b- -glucopyranoside

D

David Rabuka, Ole Hindsgaul*

Department of Chemistry, Uni6ersity of Alberta, Edmonton, AB, Canada T6G 2G2

Received 9 March 2002; accepted 4 May 2002

Dedicated to Professor Derek Horton on the occasion of his 70th birthday

Abstract

All six regioisomeric monophosphates of octyl b-

D

-galactopyranosyl-(14)-2-acetamido-2-deoxy-b-D-glucopyranoside have

been chemically synthesized and characterized by high-resolution H, ¹³C and ³¹P NMR spectroscopy. Phosphorylation causes

1

characteristic downﬁeld shifts of the nucleus at the substituted site in the H and ¹³C NMR signals and resulted in a unique ³¹P

1

Keywords: Disaccharide-phosphate; Monophosphates; N-acetyllactosamine; NMR spectroscopy; Phosphorylation

1. Introduction

phorylated oligosaccharides encountered. Preliminary

characterization of complex oligosaccharides usually

1

Phosphorylation is ubiquitous in nature and often

used transiently in signaling,¹but very rarely are phos-

relies on H NMR spectroscopy, where any phosphates

(or sulfates) would be ‘‘invisible’’.²The availability of

well-characterized

standards

of

phosphorylated

oligosaccharides and especially those of the ubiquitous

terminal N-acetyllactosamine (LacNAc) units should

therefore facilitate the detection of species should they

occur, or at least eliminate their possible presence in

unidentiﬁed anionic oligosaccharrides.

1

Herein we report the synthesis and H, ¹³C and ³¹P

NMR characterization of the four monophosphates of

octyl b-D-Glc, model compounds for methodology de-

velopment, and the six regioisomeric monophosphates

of octyl b-LacNAc (Fig. 1).

2. Results and discussion

Chemical synthesis.—The four isomeric monophos-

phates of octyl b-D-Glc and the six isomeric monophos-

Fig. 1. Synthetic targets.

phates of octyl b-LacNAc were prepared using reported

synthetic methods. The simpler monosaccharide phos-

phates were prepared ﬁrst to establish the reaction

conditions for selective protection, phosphorylation and

* Corresponding author. Tel: +1-780-4924171; fax: +1-

780-4927705

E-mail address: ole.hindsgaul@ualberta.ca (O. Hindsgaul).

PII: S0008-6215(02)00178-7

2128

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

derivatives. In order to determine the stereochemistry

of the two regioisomers, small amounts of 12 and 13

were acetylated to afford 12% and 13%, which could then

be characterized. Further reaction with p-methoxyben-

zyl chloride (PMB-Cl) gave 14 (44%) and 15 (51%).

Regioselective opening of the benzylidene acetals 14

and 15 gave 16 (58%) and 17 (54%), respectively. O-

Benzylation gave the fully protected 18 (91%) and 19

(95%). Selective removal of the PMB ether provided 20

(63%) and 21 (69%) (Scheme 1). Phosphoryation of

octyl 2,3,4-tri-O-benzyl-b-

D

-glucopyranoside (22),⁴oc-

tyl 2,3,6-tri-O-benzyl-b-

D

-glucopyranoside (23),⁵20 and

21 using diphenyl phosphorochloridate and DMAP in

pyridine⁶gave the phosphoric triesters 24 (60%), 25

(63%), 26 (92%) and 27 (87%). Deprotection of the

benzyl ethers and phenyl phosphoesters then provided

the phosphates 1 (90%), 2 (84%), 3 (90%) and 4 (78%)

(Scheme 2).

Scheme 1. Reagents: (a) Bu₄Br, 15% NaOH, BnBr, DCM. (b)

PMB–Cl, NaH, DMF. (c) LiAlH₄, AlCl₃, Et₂O. (d) BnBr,

NaH, DMF. (e) DDQ. DCM.

The synthesis of the selectively blocked disaccharides

required three unique acceptors and three unique

donors. Octyl 4,6-O-benzylidene-2-deoxy-2-phthal-

imido-b-

-glucopyranoside (28)⁷was treated with allyl

D

chloride and sodium hydride in DMF to afford 29

(56%), followed by regioselective opening of the benzyl-

idene acetal to give 30 (96%) (Scheme 3). Octyl 3,4,6-

tri-O-acetyl-2-deoxy-2-phthalimido-b-D-glucopyranoside

(31)⁶was deacetylated and reacted with anisaldehyde

dimethyl acetal and p-toluenesulfonic acid monohy-

drate in acetonitrile to afford 32 (38%). The free OH

group in 32 was converted to the benzyl ether, and the

p-methoxybenzylidene acetal was then regioselectively

opened to give 34 (62%) (Scheme 3). Treatment of ethyl

Scheme 2. Reagents: (a) (PhO)₂POCl, DMAP, pyr. (b) (i) 5%

Pd–C, 95% EtOH, H₂. (ii) PtO₂, 95% EtOH, H₂.

2,6-di-O-acetyl-3,4-di-O-isopropylidene-1-thio-b-D-

galactopyranoside (35)⁸with 70% acetic acid gave 36

(95%). The stannylidene intermediate was prepared,

and regioselective alkylation with allyl bromide af-

forded three compounds that were isolated from the

1

mixture. H NMR analysis revealed that, although the

regioselective alkylation was successful, the acetate pro-

tecting groups had migrated during the course of the

reaction. All three compounds were pooled and then

O-acetylated resulting in the formation of the single

compound 37 (77%) (Scheme 4).

Scheme 3. Reagents: (a) AllCl, DMF, NaH (56%). (b)

NaCNBH₃, HCl Et₂O, THF (96%). (c) (i) NaOMe–MeOH.

(ii) pTsOH, DMF, anisaldehyde dimethyl acetal (90% over

two steps). (d) BnBr, NaH, DMF (81%). (e) NaCNBH₃,

CF₃COOH, DMF, 0 °C, (82%).

Glycosylation of octyl 3,6-di-O-benzyl-2-deoxy-2-ph-

thalimido-b-

D

-glucopyranoside

(38)⁷

with

ethyl

4,6-O-benzylidene-thio-1-b-

D

-galactopyranoside (39)⁹

afforded 40 (62%). Deacetylation gave 41, which was

reprotected by benzylation at OH-3 and OH-4 to afford

42 (66%). The benzylidene acetal was removed using

80% acetic acid to give 43 (92%). The 6-OH group was

selectively protected as the trityl ether affording 44

(quant). The 4-OH group was protected as the benzyl

ether to give 45 (84%). The trityl group was selectively

removed using a solution of 5% triﬂuoroacetic acid and

5% triisopropylsilane to afford 46 (97%). Removal of

the phthalimido group, followed by N-acetylation, gave

deprotection that would later be applied to the more

complex LacNAc targets.

Synthesis of the selectively blocked monosaccharides

began from known octyl 4,6-O-benzylidene-b-D-

glucopyranoside (11),³which was subjected to selective

benzylation using phase-transfer conditions to afford

the 3-O-benzyl 12 (13%) and 2-O-benzyl 13 (24%)

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2129

47 (86%) (Scheme 5). The regioselective opening of the

acetal ring in 42 afforded 48 (57%). The removal of the

phthalimido group and N-acetylation then gave 49

(90%) (Scheme 6).

Glycosylation of octyl 3,6,-di-O-benzyl-2-deoxy-2-

phthalimido-b-

-glucopyranoside (38)⁷with 37 af-

D

forded 50 (81%). Deactylation, followed by

benzylation, afforded 51 (27%). The allyl protecting

group was selectively removed with palladium chloride

to give 52 (88%), followed by the removal of the

phthalimido group and N-acetylation to give 53 (94%)

(Scheme 6).

Glycosylation of octyl 3,6,-di-O-benzyl-2-deoxy-2-

phthalimido-b-

D

-glucopyranoside (38)⁷with ethyl 2-O-

acetyl-3,4,6-tri-O-benzyl-1-thio-b-

D

-galactoside (54)¹⁰

,

Scheme 6. Reagents: (a) NaCNBH₃, HCl Et₂O, sieves 4 A,

THF (57%). (b) (i) NH₂CH₂CH₂NH₂, t-BuOH. (ii) Ac₂O,

MeOH, Et₃N (90% over two steps). (c) NIS, AgOTf, sieves 4

A, DCM (81%). (d) (i) NaOMe, MeOH. (ii) BnBr, NaH,

Bu₄NI (27% over two steps). (e) PdCl₂, DCM, (88%). (f) (i)

NH₂CH₂CH₂NH₂, t-BuOH. (ii) Ac₂O, MeOH, Et₃N (94%

over two steps).

Scheme 4. Reagents: (a) 70% AcOH, CH₃CN, 60 °C (95%).

(b) (i) Bu₂SnO, tol. (ii) AllBr, Bu₄NBr. (iii) Ac₂O, pyr (77%

over three steps).

,

afforded 55 (81%). The phthalimido and acetate groups

were then removed concurrently, followed by N-acety-

lation to provide 56 (92%) (Scheme 7).

Glycosylation of 34 with 2-O-acetyl-3,4,6-tri-O-ben-

zyl-1-thio-b-

-galactopyranoside (54)¹⁰gave 57 (88%)

D

which was O-deacetylated to afford 58 (77%). O-Benzy-

lation then yielded 59 (35%). Selective deprotection

with DDQ afforded 60 (59%), and removal of the

phthalimido group, followed by N-acetylation gave 61

(82%) (Scheme 7).

Glycosylation of 30 with 54¹⁰gave 62 (80%). Re-

moval of the acetate afforded 63 (78%), which was

benzylated to give 64 (45%). Selective removal of the

allyl protecting group with palladium chloride gave 65

(95%). Removal of the phthalimido group and N-acety-

lation afforded 66 (96%) (Scheme 8).

The six monohydroxy octyl b-LacNAc compounds

5–10 were functionalized and deprotected to give their

respective phosphates. Compounds 47 and 53 were

phosphorylated using the conditions established for the

octyl b-Glc compounds to afford 67 (72%) and 68

(80%), respectively. Deprotection gave the ﬁnal target

compounds 5 (65%) and 7 (56%) (Scheme 9). Attempts

to phosphorylate 66 under the same conditions were

,

Scheme 5. Reagents: (a) NIS, AgOTf, sieves 4 A, DCM

(62%). (b) NaOMe, MeOH (70%). (c) BnBr, NaH, Bu₄NI

(66%). (d) 80% AcOH, 80 °C (92%). (e) TrCl, i-Pr₂NEt, DCM

(quant.). (f) BnBr, NaH, Bu₄NI (84%). (g) 5% TFA, 5% TIS,

DCM (97%). (h) (i) NH₂CH₂CH₂NH₂, t-BuOH. (ii) Ac₂O,

MeOH, Et₃N (86% over two steps).

2130

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

unsuccessful, and a different approach¹¹had to be used.

Compounds 49, 56, 61 and 66 were reacted with N,N-

diethylphosphoramidite and 1,2,4-triazole in DCM to

afford the phosphitylated compounds 69 (59%), 70

(89%), 71 (98%) and 72 (45%), which were oxidized to

the phosphates 73 (79%), 74 (87%), 75 (85%) and 76

(66%). Hydrogenolysis gave the ﬁnal target compounds

6 (73%), 8 (67%), 9 (73%) and 10 (71%) (Scheme 10).

NMR characterization.—The proton chemical shift

and coupling constants for the monosaccharides 1–4

and the disaccharides 5–10 are presented in Tables

1–4. The chemical changes induced by the presence of

a phosphate are presented in Figs. 2 and 3. All samples

were run in a basic buffer of sodium deuteroxide (0.045

M) and sodium bicarbonate-d₁(0.05 M) in D₂O to

ensure complete ionization of the phosphate.

The changes in proton chemical shift due to phos-

phoryation are strongest at the site of substitution, with

changes in the chemical shift typically 0.3–0.6 ppm

downﬁeld for the secondary alcohols and 0.2 ppm for

the primary alcohols. The deshielding effects dramati-

,

Scheme 8. Reagents: (a) NIS, AgOTf, sieves 4 A, DCM

(80%). (b) NaOMe, MeOH (78%). (c) BnBr, NaH, Bu₄NI

(45%). (d) PdCl₂, DCM (95%). (e) (i) NH₂CH₂CH₂NH₂,

t-BuOH. (ii) Ac₂O, MeOH, Et₃N (96%).

Scheme 9. Reagents: (a) (PhO)₂POCl, DMAP, pyr. (b) (i)

Pd–C, H₂, 95% EtOH. (ii) PtO₂, H₂, 95% EtOH.

Scheme 10. Reagents: (a) (BnO)₂PN(Et)₂, 1,2,4-triazole.

DCM. (b) 30% H₂O₂, THF. (c) Pd–C, H₂, 95% EtOH.

,

Scheme 7. Reagents: (a) NIS, AgOTf, 4 A MS, DCM (81%).

(b) (i) NH₂CH₂CH₂NH₂, t-BuOH. (ii) Ac₂O, MeOH, Et₃N

,

(92%, two steps). (c) NIS, AgOTf, 4 A MS, DCM (88%). (d)

cally drop off with distance from the site of substitution

with immediate neighboring sites exhibiting changes in

the 0.1–0.2 ppm range or demonstrating no change

NaOMe, MeOH (77%). (e) BnBr, NaH, Bu₄NI, DMF (35%).

(f) DDQ, DCM (59%). (g) (i) NH₂CH₂CH₂NH₂, t-BuOH. (ii)

Ac₂O, MeOH, Et₃N (82%, two steps).

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2131

Table 1

¹H chemical shifts ^aof phosphorylated octyl b-Glc monosaccharides ^b,c

H-1

H-2

H-3

H-4

H-5

H-6a

H-6b

Octyl b-Glc

4.37

4.43

4.44

4.50

4.49

3.27

3.30

3.34

3.70

3.47

3.48

3.65

3.94

3.67

3.43

3.59

3.81

3.47

3.41

3.38

4.02

3.46

3.47

3.46

3.86

3.96

3.83

3.89

3.91

3.77

3.44

3.79

3.69

6-Phosphate 1

4-Phosphate 2

3-Phosphate 3

2-Phosphate 4

^aChemical shifts are referenced to external 0.1% acetone at 2.225 ppm.

^bAll data were recorded on a 600 MHz Varian Inova spectrometer in D₂O buffered with 0.05 M NaDCO₃/0.045 M NaOD.

The temperature was 30.090.1 °C.

^cGeminal protons are not assigned stereospeciﬁcally. The higher chemical shift was arbitrarily assigned to H-6a.

with the exception of phosphorylation at a primary

alcohol. The H NMR spectra of the 6-phosphate of

tion of the 6%-phosphate, which was a doublet of dou-

blets. The 4%-phosphate showed the most dramatic

downﬁeld shift.

1

octyl-Glc (9) showed a relatively large downﬁeld shift

of H-4, as did the H-4% of octyl b-LacNAc 6%-phosphate

(5). The deshielding may be due to the spacial proxim-

ity of the phosphate at the 6-position and the proton at

the 4-position. A downﬁeld shift can also be observed

In conclusion, the six monophosphate esters of octyl

1

b-LacNAc were chemically synthesized. Their H, ¹³C

and ³¹P NMR spectra reveal characteristic chemical

shifts and/or coupling constants that should prove use-

ful in detecting (or excluding) the presence of these

structures in complex oligosaccharides isolated from

natural sources.

1

for H-1% in the H spectra of octyl b-LacNAc 6-phos-

phate (9), again possibly due to the spacial proximity of

the negatively charged phosphate and H-1%.

The analysis of the coupling constants for the phos-

phorylated octyl b-LacNAc compounds 5–10 is

severely hampered by spectral overlap and higher order

effects. The chemical shifts of H-2, H-3, and H-4 are

almost identical for many of the compounds, leading to

higher order coupling in the H-1 signal. Trends in

coupling constants are difﬁcult to discern with respect

to the position of substitution.

3. Experimental

General methods.—Analytical TLC was performed

on Silica Gel 60-F₂₅₄(E. Merck, Darmstadt) with detec-

tion by charring with 5% H₂SO₄in EtOH or ninhydrin.

All commercial reagents were used as supplied, unless

otherwise stated. Column chromatography was per-

formed on Silica Gel 60 (E. Merck, 40–63 mm, Darm-

stadt). Millex-GV (0.22 mm) ﬁlter units were from

Millipore (Missisauga, ON). C₁₈Sep-Pak sample prepa-

ration cartridges were from Waters Associates (Mis-

The ¹³C chemical shifts for compounds 1–4 are

summarized in Table 5. The changes due to the substi-

tution are approximately 3–4 ppm, with the effects

being very site speciﬁc. Very little change was observed

in the ¹³C chemical shifts for any of the unsubstituted

positions. The ¹³C chemical shifts of the phosphory-

lated octyl b-LacNAc compounds 5–10 and the unsub-

stituted octyl b-LacNAc are presented in Table 6. The

effect of phosphorylation is very complex, suggesting

that conformational changes may accompany phospho-

rylation since no clear pattern of change on phosphory-

lation is apparent.

1

sisauga, ON). H NMR spectra were recorded at 300

MHz (Varian Inova 300), 500 MHz (Varian Unity 500)

or 600 MHz (Varian Inova 600). ¹³C NMR spectra

Table 2

¹H coupling constants ^aof phosphorylated octyl b-Glc

b,c,d

monosaccharides

The ³¹P chemical shifts and coupling constants for

compounds 1–4 are shown in Table 7. The 6-phosphate

had the expected ‘‘doublet of doublet’’ coupling pat-

tern, while the other phosphates were doublets due to

three-bond coupling with vicinal protons. The ³¹P

chemical shifts and coupling constants of the phospho-

rylated octyl b-LacNAc compounds 5–10 are presented

in Table 8. The proton–phosphorous coupling of the

6-phosphate was too small to be observed resulting in a

broad singlet. All the other coupling patterns were as

expected, with all signals being doublets with the excep-

J_1,2J_2,3J_3,4J_4,5J_5,6aJ_5,6bJ_6a,6b

Octyl b-Glc

8.0 8.4 8.8 8.9 2.4 4.8 12.2

8.0 9.1 9.3 9.5 3.5 2.6 11.3

8.1 9.3 9.0 9.7 2.4 4.9 12.8

6-Phosphate 1

4-Phosphate 2

3-Phosphate 3

2-Phosphate 4

d

8.2 8.4 8.8

7.5

2.6

11.0

d

9.8 9.8 2.2 6.1 12.3

^a,b,cSee footnotes a,b,c, for Table 1. J-values are in Hz.

^dDue to spectral overlap, the coupling constants could not

be accurately determined.

2132

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

Table 3

¹H chemical shifts ^aof phosphorylated octyl b-LacNAc disaccharides ^b,c

H-1 H-2 H-3 H-4 H-5 H-6a H-6b H-1% H-2% H-3% H-4% H-5% H-6a% H-6b%

Octyl b-LacNAc

6%-Phosphate 5

4%-Phosphate 6

3%-Phosphate 7

2%-Phosphate 8

6-Phosphate 9

3-Phosphate 10

4.64 3.91 3.75 3.71 3.56 3.97

4.50 3.68 3.70 3.69 3.56 3.97

4.50 3.69 3.68 3.66 3.56 3.96

4.50 3.71 3.73 3.74 3.56 3.97

4.50 3.71 3.73 3.70 3.62 4.05

4.52 3.71 3.79 3.81 3.65 4.04

4.48 3.68 4.19 3.91 3.62 3.98

3.82

3.81

3.82

3.83

3.88

4.04

3.81

4.45

4.47

4.54

4.53

4.66

4.47

3.53

3.52

3.61

3.66

3.95

3.44

3.52

3.64

3.67

3.78

4.23

3.78

3.70

3.67

3.91

4.03

4.38

4.03

3.90

3.91

4.03

3.67

3.81

3.61

3.69

3.61

3.66

3.81

3.69

3.88

3.75

3.76

3.74

3.88

3.69

3.86

3.75

3.76

3.74

3.86

^a,b,cSee footnotes a,b,c, for Table 1.

Table 4

¹H coupling constants ^aof phosphorylated octyl b-LacNAc disaccharides ^b,c

J_1,2J_2,3J_3,4J_4,5J_5,6aJ_5,6bJ_6a,6bJ_1%,2%

J_2%,3%

J_3%,4%

J_4%,5%

J_5%,6a%

J_5%,6b%

J_6a%,6b%

d

Octyl b-LacNAc

6%-Phosphate 5

4%-Phosphate 6

3%-Phosphate 7

2%-Phosphate 8

6-Phosphate 9

3-Phosphate 10

7.9

7.7

7.1

8.1

8.0

8.4

8.3

2.4

2.3

2.2

2.0

5.1

6.5

12.5

12.2

12.1

7.8

7.9

7.7

7.9

7.7

8.0

7.5

10.0

3.3

3.6

1.1

3.3

3.5

9.2

10.0

d

5.1

d

8.4

9.2

10.2

9.9

d

1.5

12.7

d

8.8

9.4

9.2

9.4

9.2

2.6

12.3

^a,b,cSee footnotes a,b,c, for Table 1. J-values are in Hz.

^dDue to spectral overlap, the coupling constants could not be determined with accuracy.

Fig. 2. ¹H NMR chemical shift changes (in ppm) induced by phosphate substitution at different positions of octyl b-Glc. Chemical

shift changes are quoted in ppm relative to the unsubstituted octyl b-Glc. Only changes larger than 90.01 are shown.

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2133

1

Fig. 3. H NMR chemical shift changes (in ppm) induced by phosphate substitution at different positions of octyl b-LacNAc.

Chemical shift changes are quoted in ppm relative to the unsubstituted octyl b-LacNAc. Only changes larger than 90.01 are

shown.

were recorded either at 75 MHz (Bruker AM-300) or

125 MHz (Varian Unity 500). ³¹P NMR spectra were

recorded at 202 MHz (Varian Unity 500). The proton

Table 5

¹³C chemical shifts ^aof phosphorylated octyl b-Glc monosac-

chemical shifts were referenced to solvent residual

peaks for solutions in CDCl₃(CHCl₃, l 7.26), CD₃OD

(CHD₂OD l 5.32) or external 1% acetone (l 2.225).

The carbon chemical shifts were referenced to solvent

signals for solutions in CDCl₃(l 77.06), CD₃OD (l

53.80) or external 1% acetone (l 31.07). The phospho-

rous chemical shifts were referenced to external 5%

phosphoric acid (l 0.00). High-resolution electrospray-

ionization (HRESIMS) mass spectra were recorded on

a Micro-Mass ZabSpec Hydroid Sector-TOF. Micro-

analyses were carried out by the analytical services at

the department of Chemistry at the University of Al-

berta. Melting points are uncorrected. Dichloro-

methane (DCM) distilled from CaH₂was used as the

solvent for glycosidation.

charides ^b

C-1

C-2 C-3 C-4 C-5 C-6

Octyl b-Glc

102.8 73.8 76.9 70.1 76.5 61.7

103.6 73.8 76.3 69.3 75.3 64.5

103.0 74.2 76.9 73.4 75.9 61.4

103.0 73.8 81.7 70.3 76.5 61.7

102.1 76.9 77.7 70.3 76.4 61.6

6-Phosphate 1

4-Phosphate 2

3-Phosphate 3

2-Phosphate 4

^aChemical shifts are referenced to external 0.1% acetone at

31.07 ppm.

^bAll data were recorded on a 500 MHz Varian Unity

spectrometer in D₂O buffered with 0.05 M NaDCO₃/0.045 M

NaOD. The temperature was 30.090.1 °C.

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D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

Table 6

¹³C chemical shifts ^aof phosphorylated octyl b-LacNAc disaccharides ^b

C-1

C-2

C-3

C-4

C-5

C-6

C-1%

C-2%

C-3%

C-4%

C-5%

C-6%

Octyl b-LacNAc

6%-Phosphate 5

4%-Phosphate 6

3%-Phosphate 7

2%-Phosphate 8

6-Phosphate 9

3-Phosphate 10

103.5

101.9

101.6

102.1

102.0

102.7

57.6

55.8

56.2

56.5

55.6

55.9

56.3

75.0

73.2

73.1

73.2

73.3

76.2

73.5

81.9

73.2

79.7

78.2

75.3

79.0

74.7

77.3

75.7

75.5

75.7

75.3

76.6

62.8

61.1

60.8

60.6

62.9

61.7

105.9

104.1

104.0

103.8

103.5

102.0

73.4

72.8

72.4

71.8

74.5

71.8

71.7

75.6

80.0

75.6

77.6

74.4

73.6

71.0

68.0

71.7

69.1

68.8

69.5

69.7

77.9

74.9

73.8

79.3

80.6

74.3

76.0

62.8

65.7

61.4

62.9

61.7

61.9

61.7

^a,bSee footnotes for Table 5.

Octyl 3-O-benzyl-4,6-O-benzylidene-i-

oside (12) and octyl 2-O-benzyl-4,6-O-benzylidene-i-

glucopyranoside (13).—Octyl 4,6-O-benzylidene-b-

D

-glucopyran-

addition of p-methoxybenzyl chloride (450 mL, 3.0

mmol). The solution was stirred for an additional 2 h,

and ice-water was added to decompose the excess NaH.

The reaction mixture was diluted with DCM, washed

with water, dried over sodium sulfate and concentrated

under reduced pressure. The resulting solid was recrys-

tallized in isopropyl alcohol to give 14 (390 mg, 44%) as

a white solid: [h]_D+29.5° (c 1.2, CHCl₃); mp 83–

D

-

D

glucopyranoside (11)³(4.71 g, 12.4 mmol) was dissolved

in DCM (200 mL), and tetrabutylammonium bromide

(2.00 g, 6.2 mmol) was added, followed by 15% NaOH

(15 mL) and benzyl bromide (2.2 mL, 18 mmol). The

solution was stirred at rt for 48 h, washed successively

with water and brine, dried over sodium sulfate and

concentrated under reduced pressure. Column chro-

matography of the resulting clear oil (25:1 toluene–

EtOAc) gave compound 12 (730 mg, 12.5%), compound

13 (1.42 g, 24.0%) and a mixture of 12 and 13 (500 mg,

8.5%) as white solids. Compounds 12 and 13 (10 mg)

were dissolved in pyridine (1 mL) and Ac₂O (0.5 mL)

and stirred at rt for 1 h. Water (1 mL) was added to the

mixture, followed by extraction with DCM. The solu-

tion was dried over sodium sulfate and concentrated

under reduced pressure to afford a white solid. Column

chromatography (10:1 hexane–EtOAc) resulted in the

separation of the acetylated products, 12% and 13%. 12%:

¹H NMR (CDCl₃): l 7.43–7.25 (10 H, Ph), 5.44 (s, 1

H, PhCHO₂), 5.28 (dd, 1 H, J_2,3=J_3,49.3 Hz, H-3),

4.86, 4.63 (d, 1 H, J 11.9 Hz, PhCH₂), 4.57 (d, 1 H, J_1,2

7.7 Hz, H-1), 4.33 (dd, 1 H, J_5,6b4.8, J_5,6a10.5 Hz,

H-5), 3.93 (dt, 1 H, J 6.4, 9.4 Hz, OCH₂CH₂), 3.77 (dd,

1 H, J_6a,6b10.0 Hz, H-6a), 3.62–3.38 (4 H, H-2, H-4,

H-6b, OCH₂CH₂), 1.95 (s, 3 H, CH₃, acetyl), 1.72 (2 H,

OCH₂CH₂), 1.34–1.20 (10 H, CH₂, octyl), 0.85 (t, 3 H,

1

84 °C: H NMR (CDCl₃): l 7.47 (2 H, Ph), 7.40–7.22

(10 H, Ph), 6.85 (d, 2 H, J 7.5 Hz, Ph), 5.55 (s, 1 H,

PhCHO₂), 4.93, 4,82, 4.78, 4.69 (d, 1 H, J 11.5 Hz,

PhCH₂), 4.48 (d, 1 H, J_1,27.7 Hz, H-1), 4.35 (dd, 1 H,

J_5,6b4.9, J_5,6a10.5 Hz, H-5), 3.91 (dt, 1 H, J 6.4, 9.4 Hz,

OCH₂CH₂), 3.79 (5 H, H-3, H-4, OCH₃), 3.68 (dd, 1 H,

J_6a,6b8.1 Hz, H-6a), 3.55 (dt, 1 H, J 9.4, 6.4 Hz,

Table 7

³¹P chemical shifts ^aand coupling constants of octyl b-Glc

monosaccharides ^b

Octyl b-Glc 6-Phosphate 1

Octyl b-Glc 4-Phosphate 2

Octyl b-Glc 3-Phosphate 3

Octyl b-Glc 2-Phosphate 4

4.98

4.63

4.58

3.92

dd, 7.1 Hz

d, 8.4 Hz

d, 7.0 Hz

d, 6.8 Hz

^aChemical shifts are referenced to external 5% phosphoric

acid at 0.0 ppm.

^bAll data were recorded on a 500 MHz Varian Unity

spectrometer in D₂O buffered with 0.05 M NaDCO₃/0.045 M

NaOD. The temperature was 30.090.1 °C

1

J 7.0 Hz, CH₃, octyl). 13%: H NMR (CDCl₃): l 7.43–

7.21 (10 H, Ph), 5.58 (s, 1 H, PhCHO₂), 4.99 (dd, 1 H,

J_1,28.1, J_2,38.7 Hz, H-2) 4.96, 4.65 (d, 1 H, J 11.7 Hz,

PhCH₂), 4.43 (d, 1 H, H-1), 4.34 (dd, 1 H, J 5.0, 10.4

Hz, H-5), 3.87–3.67 (4 H, H-3, H-6a, H-6b,

OCH₂CH₂), 3.58–3.51 (2 H, H-4, OCH₂CH₂), 1.95 (s, 3

H, CH₃, acetyl), 1.55 (2 H, OCH₂CH₂), 1.35–1.18 (10

H, CH₂, octyl), 0.88 (t, 3 H, J 7.0 Hz, CH₃, octyl).

Octyl 3-O-benzyl-4,6-O-benzylidene-2-O-p-methoxy-

Table 8

³¹P chemical shifts ^aand coupling constants of octyl b-Lac-

NAc disaccharides ^b

Octyl b-LacNAc 6%-phosphate 5

Octyl b-LacNAc 4%-phosphate 6

Octyl b-LacNAc 3%-phosphate 7

Octyl b-LacNAc 2%-phosphate 8

Octyl b-LacNAc 6-phosphate 9

Octyl b-LacNAc 3-phosphate 10

4.64

5.43

4.44

4.13

4.10

4.18

dd, 6.5

d, 9.7

d, 8.4

d, 7.9

s

benzyl-i- -glucopyranoside (14).—Compound 12 (720

D

mg 1.5 mmol) was dissolved in DMF (5 mL), and NaH

(118 mg, 60% dispersion in oil, 3.0 mmol) was added.

The suspension was stirred at rt for 30 min, followed by

d, 9.4

^a,bSee footnotes a,b for Table 7.

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2135

OCH₂CH₂), 3.46–3.33 (2 H, H-2, H-6b), 1.72 (2 H,

OCH₂CH₂), 1.34–1.20 (10 H, CH₂, octyl), 0.85 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 159.3,

138.7, 137.4, 130.6 (aromatic quat), 129.8, 128.9, 128.3,

128.0, 127.6, 126.1, 113.8 (aromatic CH), 104.3 (C-1),

101.2 (PhCHO₂), 81.7, 81.6, 81.0, 75.1, 75.0, 70.7, 68.9,

66.1 (C-2, C-3, C-4, C-5, C-6, OCH₂CH₂, PhCH₂×2),

55.3 (OCH₃), 31.9, 29.9, 29.5, 29.3, 26.2, 22.7 (CH₂

octyl), 14.1 (CH₃octyl). Anal. Calcd for C₃₈H₅₂O₆

(604.90): C, 72.44; H, 8.16. Found: C, 72.68; H, 7.91.

Octyl 2-O-benzyl-4,6-O-benzylidene-3-O-p-methoxy-

OCH₂CH₂), 3.41–3.30 (2 H, H-2, H-6b), 1.87 (bs, 1 H,

OH), 1.64 (2 H, OCH₂CH₂), 1.50–1.22 (10 H, CH₂,

octyl), 0.94 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C NMR

(CDCl₃): l 153.1, 130.6, 129.8 (aromatic quat), 128.5,

128.4, 128.1, 127.9, 127.6, 113.8 (aromatic CH), 103.8

(C-1), 84.6, 82.0, 77.7, 75.6, 75.1, 75.0, 74.6, 70.0, 62.2

(C-2, C-3, C-4, C-5, C-6, OCH₂CH₂, PhCH₂×3), 55.3

(OCH₃), 31.9, 29.9, 29.5, 29.3, 26.2, 22.7 (CH₂, octyl),

14.1 (CH₃, octyl). Anal. Calcd for C₃₈H₅₄O₆(606.83):

C, 72.94; H, 8.16. Found: C, 72.43; H, 8.47.

Octyl

2,4-di-O-benzyl-3-O-p-methoxybenzyl-i-D-

benzyl-i-

D

-glucopyranoside (15).—Compound 13 (1.42

glucopyranoside (17).—Compound 17 (430 mg, 54%)

was synthesized from 15 (800 mg, 14.0 mmol), lithium

aluminum hydride (532 mg, 140 mmol), and aluminum

trichloride (1.82 g, 140 mmol) as described for 16: mp

70–71 °C; [h]_D+2.9° (c 1.0, CHCl₃); ¹H NMR

(CDCl₃): l 7.38–7.19 (12 H, Ph), 6.81 (d, 2 H, J 7.6 Hz,

Ph), 4.93, 4.85, 4.83, 4.72, 4.71, 4.61 (d, 1 H, J 11.0 Hz,

PhCH₂), 4.41 (d, 1 H, J_1,27.8 Hz, H-1), 3.90 (dt, 1 H,

J 6.4, 9.4 Hz, OCH₂CH₂), 3.86–3.68 (5 H, H-4, H-5,

OCH₃), 3.64 (dd, 1 H J_2,3=J_3,49.0 Hz, H-3), 3.57–3.48

(2 H, H-6a, OCH₂CH₂), 3.40–3.31 (2 H, H-2, H-6b),

1.86 (bs, 1 H, OH), 1.63 (2 H, OCH₂CH₂), 1.41–1.22

(10 H, CH₂, octyl), 0.88 (t, 3 H, J 7.0 Hz, CH₃, octyl);

¹³C NMR (CDCl₃): l 159.3, 138.5, 138.1, 130.8 (aro-

matic quat.), 129.6, 128.5, 128.4, 128.0, 127.9, 127.7,

113.8 (aromatic CH), 103.8 (C-1), 84.2, 82.5, 77.6, 75.0

(C-2, C-3, C-4, C-5), 75.4, 75.1, 74.9, 70.5, 62.2 (C-6,

OCH₂CH₂, PhCH₂×3), 55.3 (OCH₃), 31.8, 29.8, 29.5,

29.3, 26.2, 22.7 (CH₂, octyl), 14.1 (CH₃, octyl).

g, 3.0 mmol) was dissolved in DMF (10 mL), and NaH

(240 mg, 60% dispersion in oil, 6.0 mmol) was added.

The solution was stirred at rt for 30 min, followed by

the addition of p-methoxybenzyl chloride (850 mL, 6.0

mmol). The reaction mixture was stirred for 1 h, and

ice-water was added to decompose the excess NaH. The

solution was diluted with DCM, washed with water,

dried over sodium sulfate, and concentrated under re-

duced pressure. The resulting solid was recrystallized

from isopropyl alcohol to give 15 (900 mg, 51%) as a

white solid: mp 69–70 °C; [h]_D+30.2° (c 1.2, CHCl₃);

¹H NMR (CDCl₃): l 7.54 (2 H, Ph), 7.40–7.22 (10 H,

Ph), 6.80 (d, 2 H, J 7.5 Hz, Ph), 5.55 (s, 1 H, PhCHO₂),

4.89, 4.83, 4.75, 4.71 (d, 1 H, J 11.0 Hz, PhCH₂), 4.47

(d, 1 H, J_1,27.7 Hz, H-1), 4.35 (dd, 1 H, J 5.0, 10.4 Hz,

H-5), 3.90 (dt, 1 H, J 6.4, 9.4 Hz, OCH₂CH₂), 3.81–

3.62 (6 H, H-3, H-4, H-6a, OCH₃), 3.54 (dt, 1 H, J 9.4,

6.4 Hz, OCH₂CH₂), 3.45–3.34 (2 H, H-2, H-6b), 1.63

(2 H, OCH₂CH₂), 1.36 (10 H, CH₂, octyl), 0.87 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 159.3,

138.5, 137.4, 130.7 (aromatic quat), 129.7, 128.9, 128.3,

128.2, 127.7, 126.1, 113.7 (aromatic CH), 104.2 (C-1),

101.1 (PhCHO₂), 82.2, 81.5, 75.3, 74.8, 70.7, 68.9, 66.1

(C-2, C-3, C-4, C-5, C-6, OCH₂CH₂, PhCH₂×2), 55.3

(OCH₃), 31.9, 29.9, 29.5, 29.3, 26.2, 22.7 (CH₂, octyl),

14.1 (CH₃, octyl).

Octyl 3,4,6-tri-O-benzyl-2-O-p-methoxybenzyl-i-D-

glucopyranoside (18).—Compound 16 (130 mg, 0.20

mmol) was dissolved in dry DMF (1 mL), NaH (11 mg,

60% dispersion in oil, 0.28 mmol) was added, and the

solution was stirred at rt for 20 min. Benzyl bromide

(30 mL, 0.28 mmol) was added, and the reaction was

stirred for 3 h. Ice-water was added to decompose the

excess NaH, and the reaction was diluted with DCM

and washed with water. The organic layer was dried

with sodium sulfate and concentrated. Column chro-

matography (4:1 hexane–EtOAc) gave 18 (315 mg,

Octyl

3,4-di-O-benzyl-2-O-p-methoxybenzyl-i-D-

glucopyranoside (16).—Compound 14 (290 mg, 0.52

mmol) was dissolved in Et₂O, and lithium aluminum

hydride (200 mg, 5.2 mmol) was added. The solution

was cooled to 0 °C, and aluminum trichloride (611 mg,

5.3 mmol) in Et₂O (5 mL) was added dropwise over 30

min. The solution was warmed to rt and stirring contin-

ued for 1 h. The reaction was quenched with water (1

mL), ﬁltered through Celite, diluted with Et₂O and

washed successively with water and brine. Column

chromatography (10:1 toluene–EtOAc) gave 16 (170

mg 58%) as a white solid: mp 59–60 °C; [h]_D+8.6° (c

0.7, CHCl₃); ¹H NMR (CDCl₃): l 7.38–7.21 (12 H,

Ph), 6.82 (d, 2 H, J 7.4 Hz, Ph), 4.92, 4.85, 4.83, 4.77,

4.64, 4.61 (d, 1 H, J 11.1 Hz, PhCH₂), 4.40 (d, 1 H, J_1,2

7.9 Hz, H-1), 3.90 (dt, 1 H, J 6.3, 9.5 Hz, OCH₂CH₂),

3.84–3.68 (5 H, H-4, H-5, OCH₃), 3.63 (dd, 1 H

1

91%) as a colorless oil: H NMR (CDCl₃): l 7.35–7.21

(15 H, Ph), 7.17–7.12 (2 H, Ph), 6.91 (d, 2 H, J 7.0 Hz,

Ph), 4.91, 4.86, 4.82, 4.75, 4.64, 4.59, 4,54, 4.50 (d, 1 H,

J 11.0 Hz, PhCH₂), 4.36 (d, 1 H, J_1,27.8 Hz, H-1), 3.94

(dt, 1 H, J 6.2, 9.5 Hz, OCH₂CH₂), 3.77 (s, 3 H,

OCH₃), 3.73 (dd, 1 H J_3,42.0, J_2,39.0 Hz, H-3), 3.65

(dd, 1 H, J_4,510.8 Hz, H-4), 3.60 (dd, 1 H, J_5,6a=J_6a,6b

8.4 Hz, H-6a), 3.46–3.38 (2 H, H-5, OCH₂CH₂), 3.46–

3.38 (2 H, H-2, H-6b), 1.67 (2 H, OCH₂CH₂), 1.50–

1.22 (10 H, CH₂, octyl), 0.86 (t, 3 H, J 7.0 Hz, CH₃,

octyl). Anal. Calcd for C₄₅H₆₀O₆(682.88): C, 75.63; H,

7.97. Found: C, 75.44; H, 8.16.

Octyl 2,4,6-tri-O-benzyl-3-O-p-methoxybenzyl-i-D-

glucopyranoside (19).—Compound 19 (430 mg, 95%)

was synthesized from 17 (400 mg, 0.60 mmol) in dry

J_2,3=J_3,49.0 Hz, H-3), 3.58–3.49 (2 H, H-6a,

2136

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

DMF (4 mL) containing NaH (50 mg, 60% dispersion

in oil, 1.3 mmol) and benzyl bromide (120 mL, 1.1

mmol) as described for 18: mp 62–63 °C; [h]_D+3.8° (c

1.0, CHCl₃); ¹H NMR (CDCl₃): l 7.37–7.23 (17 H,

Ph), 6.80 (d, 2 H, J 8.7 Hz, Ph), 4.95, 4.83, 4.81, 4.71,

4.69, 4.59, 4,53, 4.51 (d, 1 H, J 11.0 Hz, PhCH₂), 4.36

(d, 1 H, J_1,27.8 Hz, H-1), 3.92 (dt, 1 H, J 6.4, 9.5 Hz,

OCH₂CH₂), 3.77 (s, 3 H, OCH₃), 3.73 (dd, 1 H, H-3),

3.64 (dd, 1 H, H-4), 3.61 (dd, 1 H, J_5,6a=J_6a,6b8.9 Hz,

H-6a), 3.56–3.49 (2 H, H-5, OCH₂CH₂), 3.47–3.41 (2

H, H-2, H-6b), 1.64 (2 H, OCH₂CH₂), 1.42–1.20 (10 H,

CH₂, octyl), 0.86 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 159.2, 138.6, 138.4, 138.3, 130.9

(aromatic quat), 129.6, 128.4, 128.3, 128.2, 128.0, 127.8,

127.7, 113.8 (aromatic CH), 103.7 (C-1), 84.5, 82.4,

78.1, 74.9 (C-2, C-3, C-4, C-5), 75.4, 75.0, 74.8, 73.5,

70.2, 69.1 (C-6, OCH₂CH₂, PhCH₂×4), 55.3 (OCH₃),

31.9, 29.9, 29.5, 29.3, 26.3, 22.7 (CH₂, octyl), 14.1 (CH₃,

octyl). Anal. Calcd for C₄₃H₅₄O₇(682.88): C, 75.63; H,

7.97. Found: C, 75.75; H, 8.27.

CH₂, octyl), 0.86 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 138.4, 138.2, 138.1 (aromatic quat.),

129.2, 129.1, 129.0, 128.7, 128.6, 128.5, 128.4, 128.3

(aromatic CH), 103.3 (C-1), 81.3, 77.4, 76.6, 74.3 (C-2,

C-3, C-4, C-5), 74.6, 74.4, 73.5, 70.1, 69.2 (C-6,

OCH₂CH₂, PhCH₂×3), 31.9, 30.0, 29.8, 29.5, 26.2,

22.7 (CH₂, octyl), 14.1 (CH₃, octyl).

Octyl 2,3,4-tri-O-benzyl-6-O-diphenoxyphosphono-i-

D

-glucopyranoside (24).—Octyl 2,3,4-tri-O-benzyl-i-D-

glucopyranoside (22)⁵(50 mg, 0.09 mmol) was dissolved

in pyridine (1 mL), and the solution was cooled to 0 °C.

To the cooled solution, DMAP (27 mg, 0.22 mmol) and

diphenylphosphorochloridate (30 mL, 0.14 mmol) were

added, and the solution was allowed to warm to rt.

After 15 h the solution was diluted with DCM, and

washed sequentially with water, sodium bicarbonate

and water, followed by concentration under reduced

pressure. Column chromatography (3:1 hexane–

EtOAc) resulted in 24 (43 mg, 60%) as an oil: [h]_D

1

−3.6° (c 0.8, CHCl₃); H NMR (CDCl₃): l 7.34–7.12

Octyl 3,4,6-tri-O-benzyl-i-

D

-glucopyranoside (20).—

(25 H, Ph), 4.93, 4.91, 4.77, 4.76, 4,69 (d, 6 H, J 11.3

Hz, PhCH₂), 4.51 (ddd, 1 H, J 1.7, 6.4, 11.0 Hz, H-6a),

4.45 (d, 6 H, J 10.8 Hz, PhCH₂), 4.38 (d, 1 H, J_1,27.8

Hz, H-1), 4.32 (ddd, 1 H, J 3.6, 7.2, 12.6 Hz, H-6b),

3.87 (dt, 1 H, J 6.4, 9.5 Hz, OCH₂CH₂), 3.63 (dd, 1 H,

Compound 18 (135 mg, 0.18 mmol) was dissolved in

DCM (2 mL), and DDQ (60 mg, 0.27 mmol) was

added. The mixture was stirred for 2 h at rt and

additional DDQ (28 mg, 0.13 mmol) was added before

stirring for an additional 2 h. The solution was diluted

with DCM and washed with water. The organic layer

was dried over sodium sulfate and concentrated under

reduced pressure. Column chromatography (4:1 hex-

ane–EtOAc) gave 20 (75 mg, 63%) as a white solid: mp

34–37 °C; [h]_D−5.6° (c 0.6, CHCl₃); ¹H NMR

(CDCl₃): l 7.45–7.18 (15 H, Ph), 4.95, 4.84, 4.62, 4.58,

4,55, 4.51 (d, 6 H, J 11.0 Hz, PhCH₂), 4.24 (d, 1 H, J_1,2

7.1 Hz, H-1), 3.91 (dt, 1 H, J 6.4, 9.5 Hz, OCH₂CH₂),

3.75 (dd, 1 H, H-3), 3.62–3.44 (5 H, H-2, H-5, H-6a,

H-6b, OCH₂CH₂), 2.17 (bs, 1 H, OH), 1.84 (2 H,

OCH₂CH₂), 1.42–1.22 (10 H, CH₂, octyl), 0.86 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 139.4,

138.9, 138.8 (aromatic quat.), 129.2, 129.1, 129.0, 128.7,

128.6, 128.5, 128.4, 128.3 (aromatic CH), 103.4 (C-1),

85.2, 78.3, 75.4, 74.2 (C-2, C-3, C-4, C-5), 75.9, 75.3,

73.7, 70.8, 69.6 (C-6, OCH₂CH₂, PhCH₂×3), 32.5,

30.3, 30.1, 29.9, 26.7, 23.4 (CH₂, octyl), 14.8 (CH₃,

octyl).

J

_2,3=J_3,48.9 Hz, H-3), 3.52–3.43 (3 H, H-4, H-5,

OCH₂CH₂), 3.39 (dd, 1 H, H-2), 1.60 (2 H, OCH₂CH₂),

1.39–1.20 (10 H CH₂, octyl), 0.86 (t, 3 H, J 7.0 Hz,

CH₃, octyl); ¹³C NMR (CDCl₃): l 150.6, 150.5 (d, J 5.5

Hz, aromatic quat), 138.5, 138.4, 137.8 (aromatic quat),

129.8, 129.7, 128.5, 128.4, 128.2, 128.1, 128.0, 127.7

(aromatic CH), 125.4, 125.3 (d, J_C,P1.5 Hz, aromatic

CH), 120.3, 120.1 (d, J_C,P4.5 Hz, aromatic CH), 103.5

(C-1), 85.5 (C-3), 82.2 (C-2), 77.1 (C-4), 76.5, 75.9, 71.5

(PhCH₂×3), 73.5 (d, J_5,P7.6 Hz, C-5), 71.4

(OCH₂CH₂), 67.7 (d, J_6,P5.9 Hz, C-6), 31.9, 29.8, 29.4,

29.3, 26.2, 22.7 (CH₂, octyl), 14.1 (CH₃, octyl). HRES-

IMS Calcd for C₄₇H₅₅NO₉Na 817.3481. Found

817.3482. Anal. Calcd for C₄₇H₅₅O₉(794.91): C, 71.01;

H, 6.97. Found: C, 71.04; H, 6.96.

Octyl 2,3,6-tri-O-benzyl-4-O-diphenoxyphosphono-i-

D-glucopyranoside (25).—Compound 25 (83 mg, 63%)

was synthesized from octyl 2,3,6-tri-O-benzyl-b-D-

glucopyranoside (23)⁴(90 mg, 0.16 mmol),

diphenylphosphorochloridate (80 mL, 0.35 mmol),

DMAP (32 mg 0.26 mmol), and pyridine (2 mL) as

described for the preparation of 24: [h]_D+3.6° (c 1.3,

Octyl 2,4,6-tri-O-benzyl-i- -glucopyranoside (21).—

D

Compound 21 (225 mg, 69%) was prepared, as a white

solid, from 19 (380 mg, 0.50 mmol) by reaction in

DCM (5 mL) with DDQ (171 mg, 0.75 mmol) as

described for the preparation of 20: mp 47–49 °C; [h]_D

1

CHCl₃); H NMR (CDCl₃): l 7.30–7.02 (25 H, Ph),

4.92, 4.86, 4.72, 4.64, (d, 4 H, J 10.8 Hz, PhCH₂), 4.62

(ddd, 1 H, J_3,4=J_4,59.3, J_4,P9.5 Hz), 4.57 (d, 1 H, J

12.0 Hz, PhCH₂), 4.43 (d, 1 H, J_1,27.5 Hz, H-1), 4.41

(d, 1 H, J 11.8 Hz, PhCH₂), 3.93 (dt, 1 H, J 6.4, 9.5 Hz,

OCH₂CH₂), 3.75–3.71 (2 H, H-3, H-6a), 3.66–3.60

(2H, H-5, H-6b), 3.52 (dt, 1 H, J 6.7, 9.5 Hz,

OCH₂CH₂), 3.50 (dd, 1 H, J_2,39.1 Hz, H-2), 1.63 (2 H,

OCH₂CH₂), 1.41–1.22 (10 H, CH₂, octyl), 0.88 (t, 3 H,

1

+14.0° (c 1.2, CHCl₃); H NMR (CDCl₃): l 7.41–7.22

(15 H, Ph), 4.88, 4.82, 4.65, 4.60, 4,58, 4.53 (d, 6 H, J

11.3 Hz, PhCH₂), 4.36 (d, 1 H, J_1,27.8 Hz, H-1), 3.92

(dt, 1 H, J 6.4, 9.5 Hz, OCH₂CH₂), 3.78–3.63 (3 H,

H-3, H-4, H-6a), 3.55–3.40 (3 H, H-2, H-5,

OCH₂CH₂), 3.25 d, 1 H, J 7.8, 9.2 Hz, H-6b), 2.40 (bs,

1 H, OH), 1.65 (2 H, OCH₂CH₂), 1.42–1.20 (10 H,

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2137

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 150.6,

150.5 (d, J_C,P5.5 Hz, aromatic quat), 138.3, 138.2

(aromatic quat), 129.7, 129.6, 128.3, 128.2, 128.1, 127.7,

127.6, 127.5, 127.3 (aromatic CH), 125.4, 125.3 (d, J_C,P

1.2 Hz, aromatic CH), 120.3, 120.1 (d, J_C,P4.8 Hz,

aromatic CH), 103.5 (C-1), 82.2 (d, J_3,P2.8 Hz, C-3),

82.0 (C-2), 77.2 (C-4), 75.0, 74.8, 73.4 (PhCH₂×3),

74.2 (d, J_5,P5.6 Hz, C-5), 70.3 (OCH₂CH₂), 69.1 (C-6),

31.9, 29.8, 29.5, 29.3, 26.2, 22.7 (CH₂, octyl), 14.1 (CH₃,

octyl). HRESIMS Calcd for C₄₇H₅₅NO₉Na 817.3481.

Found 817.3488. Anal. Calcd for C₄₇H₅₅O₉(794.91): C,

71.01; H, 6.97. Found: C, 70.84; H, 7.06.

(C-4), 75.2, 75.0, 73.5 (PhCH₂×3), 75.1 (C-5), 70.2

(OCH₂CH₂), 68.7 (C-6), 31.9, 29.5, 29.4, 29.2, 25.9,

22.7 (CH₂octyl), 14.1 (CH₃octyl). Anal. Calcd for

C₄₇H₅₅O₉(794.91): C, 71.01; H, 6.97. Found: C, 70.83;

H, 6.96.

Octyl 6-O-phosphono-i-D-glucopyranoside disodium

salt (1).—Compound 24 (43 mg, 0.05 mmol) was dis-

solved in 95% EtOH (2 mL) containing 5% Pd–C (8

mg), and the mixture was stirred under hydrogen at

ambient pressure for 15 h. TLC (5:2:1 EtOAc–hexane–

MeOH) indicated complete disappearance of starting

material. The catalyst was removed by ﬁltration, the

solvent concentrated, and the residue was redissolved in

95% EtOH (4 mL). Adams’ catalyst (PtO₂, 7 mg) was

added, and the mixture was stirred under hydrogen for

3 h. The solution was ﬁltered and concentrated. The

resulting residue was dissolved in water and puriﬁed on

a C₁₈Sep-Pak cartridge using water and MeOH. The

carbohydrate-containing fractions were pooled, concen-

trated and converted to the sodium salt by passage

through Dowex 50-X8 (Na⁺) cation-exchange resin.

Lyophilization of the eluent provided 1 (19 mg, 90%):

¹H NMR (600 MHz, D₂O (0.05 M NaDCO₃/0.045 M

NaOD)): l 4.43 (d, 1 H, J_1,28.0 Hz, H-1), 4.02 (ddd, 1

H, J_5,6a4.0, J_6a,P7.5, J_6a,6b12.2 Hz), 3.89 (dt. 1 H. J

7.0, 9.9 Hz, OCH₂CH₂), 3.64 (dt, 1 H, J 7.0, 9.9 Hz,

OCH₂CH₂), 3.59 (dd, 1 H, J_3,4=J_4,59.5 Hz, H-4), 3.48

(dd, 1 H, J_2,39.3 Hz, H-3), 3.44 (ddd, 1 H, J_5,6b2.6,

H-5), 3.27 (dd, 1 H, H-2), 1.61 (2 H, OCH₂CH₂),

1.56–1.22 (10 H, CH₂, octyl), 0.88 (t, 3 H, J 7.0 Hz,

CH₃, octyl); ¹³C NMR (D₂O): l 103.5 (C-1), 76.3 (C-3),

75.3 (d, J 10.2 Hz, C-5), 73.8 (C-2), 71.4 (OCH₂CH₂),

69.7 (C-4), 64.5 (d, J 5.9 Hz, C-6), 31.8, 29.4, 29.2, 29.1,

25.7, 22.6 (CH₂, octyl), 14.1 (CH₃, octyl); HRESIMS

Calcd for C₁₄H₂₈O₉Na₂P 417.1266. Found 417.1262.

Octyl 2,4,6-tri-O-benzyl-3-O-diphenoxyphosphono-i-

D-glucopyranoside (26).—Compound 26 (57 mg, 92%)

was synthesized from compound 20 (44 mg, 0.051

mmol), diphenylphosphorochloridate (40 mL, 0.17

mmol), DMAP (32 mg, 0.26 mmol) and pyridine (2

1

mL) as described for 24: [h]_D+3.2° (c 0.3, CHCl₃); H

NMR (CDCl₃): l 7.18–7.00 (25 H, Ph), 4.89 (d, 1 H, J

10.8 Hz, PhCH₂), 4.81 (ddd, 1 H, J_2,3=J_3,48.9, J_3,P

17.8 Hz, H-3), 4.77, 4.65, 4.59, 4.53, 4.45 (d, 1 H, J 10.8

Hz, PhCH₂), 4.20 (d, 1 H, J_1,27.6 Hz, H-1), 3.92 (dt, 1

H, J 6.6, 9.5 Hz, OCH₂CH₂), 3.77 (dd, 1 H, J_4,59.5 Hz,

H-4), 3.72–3.67 (2 H, H-6a, H-6b), 3.53 (dd, 1 H, H-2),

3.51–3.44 (2 H, H-5, OCH₂CH₂), 1.50–1.42 (2 H,

OCH₂CH₂), 1.30–1.14 (10 H, CH₂, octyl), 0.88 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 150.6,

150.5 (d, J_C,P3.2 Hz, aromatic quat), 138.2, 138.0,

137.8 (aromatic quat), 129.5, 128.4, 128.2, 128.1, 128.0,

127.9, 127.8, 127.6, 127.3 (aromatic CH), 125.0 (d, J_C,P

1.2 Hz, aromatic CH), 120.1 (d, J_C,P5.0 Hz, aromatic

CH), 103.4 (C-1), 83.9 (d, J_3,P8.0 Hz, C-3), 82.0 (d, J_2,P

2.4 Hz, C-2), 76.8 (d, J_4,P4.2 Hz, C-4), 74.5, 74.1, 73.6

(PhCH₂×3), 74.3 (C-5), 70.3 (OCH₂CH₂), 68.6 (C-6),

31.8, 29.8, 29.3, 29.2, 26.1, 22.7 (CH₂, octyl), 14.1 (CH₃,

octyl). Anal. Calcd for C₄₇H₅₅O₉(794.91): C, 71.01; H,

6.97. Found: C, 71.08; H, 6.97.

Octyl 4-O-phosphono-i-D-glucopyranoside disodium

salt (2).—Compound 2 (14 mg, 84%) was deprotected

as described in the preparation of compound 1 from

Octyl 3,4,6-tri-O-benzyl-2-O-diphenoxyphosphono-i-

1

D-glucopyranoside (27).—Compound 27 (42 mg, 87%)

compound 25 (31 mg, 0.039 mmol): H NMR (D₂O

was synthesized from compound 21 (34 mg, 0.060

mmol), diphenylphosphorochloridate (30 mL, 0.13

mmol), DMAP (22 mg, 0.18 mmol) and pyridine (2

(0.05 M NaDCO₃0.045 M NaOD)): l 4.44 (d, 1 H, J_1,2

8.1 Hz, H-1), 3.89 (dt, 1 H, J 6.4, 9.5 Hz, OCH₂CH₂),

3.85–3.78 (3 H, H-4, H-6a, H-6b), 3.68–3.64 (2 H, H-3,

OCH₂CH₂), 3.46 (dddd, 1 H, J 2.4, 4.8, 7.1, 9.7 Hz,

H-5), 3.30 (dd, 1 H, J_2,39.3 Hz, H-2), 1.64–1.58 (2 H,

OCH₂CH₂), 1.38–1.24 (10 H, CH₂, octyl), 0.85 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (D₂O): l 103.1 (C-1),

75.9 (d, J_3,P2.0 Hz, C-3), 75.9 (d, J_5,P6.0 Hz, C-5), 74.7

(d, J 6.0 Hz, C-2), 73.8 (C-4), 71.6 (OCH₂CH₂), 61.4

(C-6), 31.9, 29.6, 29.3, 29.2, 25.9, 22.9 (CH₂octyl), 14.3

(CH₃octyl); HRESIMS Calcd for C₁₄H₂₈O₉Na₂P

417.1266. Found 417.1267.

1

mL) as described for 24: [h]_D−7.0° (c 0.5, CHCl₃); H

NMR (CDCl₃): l 7.35–7.10 (25 H, Ph), 4.84 (d, 1 H, J

10.8 Hz, PhCH₂), 4.75 (d, 2 H, J 10.8 Hz, PhCH₂), 4.61

(d, 1 H, J 10.8 Hz, PhCH₂), 4.58–4.49 (4 H, H-1, H-2,

PhCH₂), 3.82–3.61 (5 H, H-3, H-4, H-6a, H-6b,

OCH₂CH₂), 3.51 (ddd, 1 H, J 2.0, 4.6, 9.8 Hz, H-5),

3.44 (dt, 1 H, J 7.3, 9.2 Hz, OCH₂CH₂), 1.48 (2 H,

OCH₂CH₂), 1.30–1.14 (10 H, CH₂, octyl), 0.88 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 150.9,

150.8 (d, J_C,P6.8 Hz, aromatic quat), 138.2, 138.1,

137.9 (aromatic quat.), 129.5, 128.4, 128.2, 128.1, 128.0,

127.8, 127.6, 127.5, 125.0 (aromatic CH), 120.2 (d, J_C,P

5.7 Hz, aromatic CH), 101.1 (d, J_1,P3.2 Hz, C-1), 83.5

(d, J_3,P4.1 Hz, C-3), 82.0 (d, J_2,P7.1 Hz, C-2), 78.0

Octyl 3-O-phosphono-i-D-glucopyranoside disodium

salt (3).—Compound 3 (7 mg, 90%) was deprotected as

described in the preparation of compound 1 from com-

pound 26 (15 mg, 0.020 mmol): ¹H NMR (D₂O (0.05 M

NaDCO₃/0.045 M NaOD)): l 4.50 (d, 1 H, J_1,28.2 Hz,

2138

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

H-1), 3.97–3.88 (3 H, H-3, H-6a, OCH₂CH₂), 3.73–

3.63 (2 H, H-5, OCH₂CH₂), 3.58–3.47 (2 H, H-4,

H-6b), 3.34 (dd, 1 H, J_2,38.4 Hz, H-2), 1.64–1.60 (2 H,

OCH₂CH₂), 1.37–1.22 (10 H, CH₂, octyl), 0.85 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (D₂O): l 103.0 (C-1),

81.7 (d, J_3,P6.1 Hz, C-3), 76.5 (C-5), 73.8 (d, J_2,P3.7

Hz, C-2), 71.9 (OCH₂CH₂), 70.3 (d, J_4,P3.7 Hz, C-4),

61.7 (C-6), 31.9, 29.6, 29.3, 29.2, 25.9, 22.8 (CH₂, octyl),

14.3 (CH₃, octyl); HRESIMS Calcd for C₁₄H₂₇O₉Na₃P

439.1086. Found 439.1082.

(CH₃octyl). Anal. Calcd for C₃₂H₃₉NO₇(553.29): C,

69.51; H, 6.96. Found: C, 69.71; H, 7.26.

Octyl 3-O-allyl-6-O-benzyl-2-deoxy-2-phthalimido-

i- -glucopyranoside (30).—Compound 29 (1.28 g, 2.39

D

mmol), sodium cyanoborohydride (753 mg, 11.95

mmol) and methyl orange indicator were dissolved in

,

dry tetrahydrofuran (THF) containing crushed 4 A

molecular sieves. The solution was cooled to 0 °C and

ethereal hydrogen chloride was added dropwise until

the red color of the solution persisted. The mixture was

warmed to rt and stirred for an additional hour, ﬁltered

through Celite, washed with water and brine and con-

centrated under reduced pressure. Column chromatog-

raphy of the resulting pink oil (5:1 hexane–EtOAc)

afforded 30 (1.24 g 96%) as a colorless oil: [h]_D+23.2°

Octyl 2-O-phosphono-i-D-glucopyranoside disodium

salt (4).—Compound 4 (4 mg, 78%) was deprotected as

described in the preparation of compound 1 from com-

pound 27 (10 mg, 0.012 mmol): ¹H NMR (D₂O (0.05 M

NaDCO₃/0.045 M NaOD)): l 4.49 (d, 1 H, J_1,27.5 Hz,

H-1), 3.92–3.86 (2 H, H-6a, OCH₂CH₂), 3.73–3.66 (4

H, H-2, H-3, H-6b, OCH₂CH₂), 3.49–3.41 (2 H, H-4,

H-5), 1.65–1.60 (2 H, OCH₂CH₂), 1.36–1.24 (10 H

CH₂octyl), 0.86 (t, 3 H, J 7.0 Hz, CH₃octyl); ¹³C

NMR (D₂O): l 103.0 (d, J_1,P7.3 Hz, C-1), 81.7 (d, J 6.1

Hz, C-3), 76.5 (C-5), 73.8 (d, J_2,P3.7 Hz, C-2), 71.9

(OCH₂CH₂), 70.3 (d, J_4,P3.7 Hz, C-4), 61.7 (C-6), 31.9,

29.6, 29.3, 29.2, 25.9, 22.8 (CH₂octyl), 14.3 (CH₃

octyl); HRESIMS Calcd for C₁₄H₂₇O₉Na₃P 439.1086.

Found 439.1089.

1

(c 0.4, CHCl₃); H NMR (CDCl₃): l 7.91–7.68 (4 H,

Phth), 7.38–7.22 (5 H, Ph), 5.60 (1 H, OCH₂CHꢀCH₂),

5.14 (d, 1 H, J_1,28.4 Hz, H-1), 5.05 (1 H, J_cis10.5 Hz,

OCH₂CHꢀCHH), 4.87 (1 H, J_trans17.0 Hz,

OCH₂CHꢀCHH), 4.63, 4.57 (d, 1 H, J 12.0 Hz,

PhCH₂), 4.22–4.13 (3 H, H-2, H-3, OCHHCHꢀCH₂),

3.97 (1 H, OCHHCHꢀCH₂), 3.84–3.71 (4 H, H-4,

H-6a, H-6b, OCH₂CH₂), 3.63 (ddd, 1 H, H-5), 3.38 (dt,

1 H, J 6.4, 9.2 Hz, OCH₂CH₂), 2.92 (bs, 1 H, OH),

1.45–1.35 (2 H, OCH₂CH₂), 1.20–0.90 (10 H, CH₂,

octyl), 0.89 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C NMR

Octyl 3-O-allyl-4,6-O-benzylidene-2-deoxy-2-phthal-

(CDCl₃):

l 137.8, 131.8 (aromatic quat.), 134.7

imido-i-

dene-2-deoxy-2-phthalimido-b-

D

-glucopyranoside (29).—Octyl 4,6-O-benzyli-

(CH₂ꢀCHCH₂O), 134.1, 128.6, 127. (aromatic CH),

117.1 (CH₂ꢀCHCH₂O), 98.5 (C-1), 79.0, 74.0, 73.7

(C-3, C-4, C-5), 73.9, 73.1 (PhCH_2,CH₂ꢀCHCH₂O),

70.8 (OCH₂CH₂,), 60.8 (C-6), 55.6 (C-2), 31.7, 29.4,

29.2, 25.9, 22.6 (CH₂, octyl), 14.1 (CH₃, octyl). Anal.

Calcd for C₃₂H₄₁NO₇(553.29): C, 69.67; H, 7.49.

Found: C, 69.37; H, 7.19.

D

-glucopyranoside (28)⁶

(2.11 g, 4.17 mmol) was dissolved in DMF (20 mL) and

cooled to 0 °C. Sodium hydride (180 mg, 60% disper-

sion in oil, 4.59 mmol) was added, and the mixture was

allowed to stir for 30 min. Allyl chloride (550 mL, 6.23

mmol) was added, and the mixture was warmed to rt

and stirred for an additional 3 h. Methanol was added

to decompose the excess NaH, and the mixture was

diluted with toluene, extracted with water and concen-

trated under reduced pressure. Column chromatogra-

phy (10:1 hexane–EtOAc) gave unreacted starting

material (520 mg 24%) and 29 (1.28 g 56%): [h]_D

Octyl 2-deoxy-4,6-O-p-methoxybenzylidene-2-phthal-

imido-i-D-glucopyranoside

(32).—Octyl

3,4,6-tri-

O-acetyl-2-deoxy-2-phthalimido-b-

D

-glucopyranoside-

(31)⁶(1.25 g, 2.3 mmol) was dissolved in dry MeOH (40

mL), and sodium (8 mg) was added. The reaction was

stirred at rt for 2 h, neutralized by adding amberlite

IR-120 (H⁺) resin, ﬁltered and concentrated. The re-

sulting yellow syrup was dissolved in MeCN, and p-

toluenesulfonic acid monohydrate (30 mg, 17.0 mmol)

and anisaldehyde dimethyl acetal (800 mL, 4.6 mmol)

were added. The solution was heated to 60 °C and

stirred for 15 h. The mixture was cooled to rt, neutral-

ized with triethylamine and concentrated. Column

chromatography (4:1 hexane–EtOAc) afforded 32 (1.03

1

+21.3° (c 0.9, CHCl₃); H NMR (CDCl₃): l 7.92–7.72

(4 H, Phth), 7.28–7.15 (5 H, Ph), 5.58 (s, 1 H,

PhCHO₂), 5.56 (1 H, OCH₂CHCH₂), 5.23 (d, 1 H, J_1,2

8.4 Hz, H-1), 5.02 (1 H, J_cis10.5 Hz, OCH₂CHꢀCHH),

4.85 (1 H, J_trans17.0 Hz, OCH₂CHꢀCHH), 4.44–4.35

(2-H, H-3, H-6a), 4.30–4.19 (2 H, H-2, OCH-

HCHꢀCH₂), 3.96 (1 H, OCHHCH=CH₂), 3.88–3.70

(3 H, H-4, H-6b, OCH₂CH₂), 3.61 (ddd, 1 H, J 4.8, 9.7,

9.7 Hz, H-5), 3.40 (dt, 1 H, J 6.6, 9.8 Hz, OCH₂CH₂),

1.52–1.30 (2 H, OCH₂CH₂), 1.20–0.92 (10 H, CH₂,

octyl), 0.80 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C NMR

(CDCl₃): l 160.1 (CO, Phth), 137.3, 131.7 (aromatic

quat.), 134.5 (CH₂ꢀCHCH₂O), 134.1, 129.0, 128.2,

126.0 (aromatic CH), 116.8 (CH₂ꢀCHCH₂O), 101.3,

99.1, 82.8, 75.2, 66.2 (C-1, C-3, C-4, C-5, PhCHO₂),

73.1, 70.1, 68.8 (C-6, OCH₂CH₂, CH₂ꢀCHCH₂O), 55.0

(C-2), 31.6, 29.3, 29.1, 29.0, 25.7, 22.6 (CH₂octyl), 14.0

1

g, 83%): H NMR (CDCl₃): l 7.92–7.70 (4 H, Phth),

7.43 (d, 2 H, J 8.2 Hz, Ph), 6.92 (d, 2 H, J 8.2 Hz, Ph),

5.51 (s, 1 H, PhCHO₂), 5.25 (d, 1 H, J_1,28.5 Hz, H-1),

4.61 (dd, 1 H, J_3,48.4, J_2,.310.4 Hz, H-3), 4.37 (dd, 1 H,

J_5,6a4.2, J_6a,6b10.4 Hz, H-6a), 4.23 (dd, 1 H, H-2),

3.86–3.77 (5 H, H-4, OCH₂CH_2,OCH₃), 3.66–3.54 (2

H, H-5, H-6b), 3.41 (dt, 1 H, J 6.5, 9.7 Hz, OCH₂CH₂),

1.48–1.30 (2 H, OCH₂CH₂), 1.23–0.92 (10 H, CH₂,

octyl), 0.82 (t, 3 H, J 7.0 Hz, CH₃, octyl).

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2139

Octyl 3-O-benzyl-2-deoxy-4,6-O-p-methoxybenzyli-

dene-2-phthalimido-i- -glucopyranoside (33).—Com-

H, J 7.5 Hz, SCH₂CH₃); ¹³C NMR (CDCl₃): l 170.7,

169.5 (CO, acetate), 137.6 (aromatic quat), 129.1, 128.2,

126.4 (aromatic CH), 101.2 (PhCHO₂), 82.8 (C-1), 73.6,

73.0, 69.8, 66.1 (C-2, C-3, C-4, C-5), 66.6 (C-6), 21.0

(SCH₂CH₃), 14.8 (SCH₂CH₃). Anal. Calcd for

C₁₂H₂₀O₇S (308.09): C, 46.74; H, 6.54. Found: C, 46.85;

H, 6.46.

D

pound 33 (778 mg, 65%) was synthesized from 32 (1.03

g, 1.91 mmol) as described for compound 18: [h]_D

1

+34.4° (c 0.7, CHCl₃); H NMR (CDCl₃): l 7.90–7.60

(4 H, Phth), 7.43–6.85 (9 H, Ph), 5.57 (s, 1 H,

PhCHO₂), 5.18 (d, 1 H, J_1,28.5 Hz, H-1), 4.78, 4.48 (d,

1 H, J 12.4 Hz, PhCH₂), 4.43–4.33 (2 H, H-3, H-6a),

4.19 (dd, 1 H, J_2,310.4 Hz, H-2), 3.88–3.72 (6 H, H-4,

H-6b, OCH₂CH_2,OCH₃), 3.61 (ddd, 1 H, J 2.3, 4.9, 9.8

Hz, H-5), 3.36 (dt, 1 H, J 6.5, 9.8 Hz, OCH₂CH₂),

1.22–1.12 (2 H, OCH₂CH₂), 1.18–0.85 (10 H, CH₂,

octyl), 0.80 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C NMR

(CDCl₃): l 160.1 (CO, Phth), 138.0, 131.7, 130.0 (aro-

matic quat), 133.8, 128.0, 127.4, 123.3 (aromatic CH),

113.6 (PhCHO₂), 101.3, 98.0, 83.1, 74.4 (C-1, C-3, C-4,

C-5), 74.0 (PhCH₂), 70.0 (OCH₂CH₂), 68.8 (C-6), 66.1

(OCH₃), 55.9 (C-2), 31.6, 29.3, 29.1, 29.0, 25.7, 22.6

(CH₂, octyl), 14.0 (CH₃, octyl). Anal. Calcd for

C₃₇H₄₃NO₈(629.74): C, 70.57; H, 6.88. Found: C,

70.48; H, 6.83.

Ethyl 2,4,6-tri-O-acetyl-3-O-allyl-1-thio-i-D-galac-

topyranoside (37).—Compound 39 (589 mg, 1.5 mmol)

was dissolved in toluene (50 mL) and was added to a

ﬂask equipped with a Dean-Stark separator containing

dibutyl tin oxide (470 mg, 1.90 mmol). The solution

was reﬂuxed for 20 h and cooled to rt. Allyl bromide (2

mL, 23.0 mmol) and tetrabutylammonium bromide

(214 mg, 0.66 mmol) were added, and the solution was

heated to 60 °C. After stirring for 2 h, the mixture was

cooled to rt and concentrated. Column chromatogra-

phy resulted in the recovery of three compounds, which

were pooled and acetylated, as described for the prepa-

ration of 37, affording 40 (447 mg 77%): mp 31–33 °C;

1

[h]_D+18.1° (c 0.9, CHCl₃); H NMR (CDCl₃): l 5.74

Octyl 3-O-benzyl-2-deoxy-6-O-p-methoxybenzyl-2-

(1 H, OCH₂CHꢀCH₂), 5.42 (d, 1 H, J_3,43.3 Hz, H-4),

phthalimido-i- -glucopyranoside (34).—Compound 33

D

5.20 (1 H, J_cis10.5 Hz, OCH₂CHꢀCHH), 5.12 (1 H,

(778 mg, 1.24 mmol) and sodium cyanoborohydride

(603 mg, 9.92 mmol) were dissolved in DMF (5 mL)

J_trans17.0 Hz, OCH₂CHꢀCHH), 5.08 (dd, 1 H, J_1,2=

J_2,39.8 Hz, H-2), 4.39 (d, 1 H, H-1), 4.12–4.04 (3 H,

H-6a, H-6b, OCHHCHꢀCH₂), 3.89 (1 H, OCH-

HCHꢀCH₂), 3.79 (dd, 1 H, J_5,6a=J_5,6b6.5 Hz, H-5),

3.49 (dd, 1 H, H-3), 2.67 (m, 2 H, SCH₂CH₃), 2.10,

2.07, 2.03 (s, 3 H, CH₃acetate), 1.24 (t, 3 H, J 7.5 Hz,

SCH₂CH₃); ¹³C NMR (CDCl₃): l 170.5, 170.3, 169.5

,

containing crushed molecular 4 A sieves. The solution

was cooled to 0 °C and triﬂuoracetic acid (1 mL) in

DMF (4 mL) was added dropwise. The solution was

allowed to warm to rt and stirred for 12 h. The reaction

was quenched by the addition of triethylamine, ﬁltered

through Celite, diluted with DCM, washed with water

and brine and concentrated under reduced pressure.

Column chromatography (5:1 hexane–EtOAc) gave 34

(CO,

acetate),

134.1

(CH₂ꢀCHCH₂O),

117.3

(CH₂ꢀCHCH₂O), 84.0 (C-1), 77.7, 74.7, 68.9, 66.4 (C-2,

C-3, C-4, C-5), 70.3 (CH₂ꢀCHCH₂O), 62.2 (C-6), 24.1

(SCH₂CH₃), 20.9, 20.8, 20.7 (CH₃, acetate), 14.9

(SCH₂CH₃). Anal. Calcd for C₁₇H₂₆O₈S (390.45): C,

52.29; H, 6.71. Found: C, 52.25; H, 6.78.

1

(636 mg, 82%): H NMR (CDCl₃): l 7.82–7.61 (4 H,

Phth), 7.24–6.82 (9 H, Ph), 5.11 (d, 1 H, J_1,28.0 Hz,

H-1), 4.74 (d, 1 H, J 12.2 Hz, PhCH₂), 4.60–4.48 (3 H,

H-2, PhCH₂), 4.25–4.08 (3 H, H-3, H-4, PhCH₂), 3.90–

3.70 (6 H, H-5, H-6a, H-6b, OCH₃), 3.63 (dt, 1 H, J

4.8, 9.4 Hz, OCH₂CH_2,), 3.34 (dt, 1 H, J 4.8, 9.7 Hz,

OCH₂CH₂), 2.96 (bs, 1 H, OH), 1.40–1.25 (2 H,

OCH₂CH₂), 1.20–0.85 (10 H, CH₂, octyl), 0.80 (t, 3 H,

J 7.0 Hz, CH₃, octyl).

Octyl 2,3-di-O-acetyl-4,6-O-benzylidine-i-

pyranosyl-(14)-3,6-di-O-benzyl-2-deoxy-2-phthal-

imido-i- -glucopyranoside (40).—Compound 40 (610

mg, 61%) was synthesized from octyl 3,6-di-O-benzyl-2-

deoxy-2-phthalimido-b-

-glucopyranoside (38)⁶(612

mg, 1.14 mmol), ethyl 2,3-di-O-acetyl-4,6-O-benzyli-

-galactopyranoside (39, 1.066 g, 1.26

D-galacto-

D

Ethyl 2,6-di-O-acetyl-1-thio-i-

(36).—Ethyl 2,6-di-O-acetyl-3,4-O-isopropylidene-1-

thio-b-

-galactopyranoside (35)⁷(790 mg, 1.7 mmol)

D-galactopyranoside

dene-1-thio-b-

D

mmol), N-iodosuccinimide (513 mg, 1.28 mmol), a cat-

D

alytic amount of silver triﬂate, dry DCM (40 mL) and

1

,

was dissolved in MeCN (2 mL) and was added to 70%

AcOH (20 mL). The solution was heated to 60 °C and

stirred for 13 h. The mixture was cooled to rt and

co-concentrated with toluene. Column chromatography

(5:1 toluene–EtOAc) yielded 39 (624 mg, 95%): [h]_D

4 A sieves as described for the preparation of 57: H

NMR (CDCl₃): l 7.80–7.60 (4 H, Phth), 7.40–6.82 (25

H, Ph), 5.40 (s, 1 H, PhCHO₂), 5.34 (dd, 1 H, J_1%,2%7.9,

J_2%,3%10.2 Hz, H-2%), 5.06 (d, 1 H, J_1,28.6 Hz, H-1), 4.97,

4.79, 4.52, 4.50 (d, 1 H, J 11.5 Hz, PhCH₂), 4.77 (dd, 1

H, J_3%,4%3.6 Hz, H-3%), 4.62 (d, 1 H, H-1%), 4.28–4.22 (2

H, H-4%, H-6a%), 4.12–4.06 (3 H, H-2, H-6a, H-6b), 3.90

(dd, 1 H, J_5%,6b%1.6, J_6a%,6b%12.3 Hz, H-6b%), 3.84–3.72 (3

H, H-3, H-4, OCH₂CH₂), 3.52 (1 H, H-5), 3.33 (dt, 1

H, J 7.0, 9.4 Hz, OCH₂CH₂), 3.21 (d, 1 H, H-5%), 2.03

(s, 6 H, CH₃, acetate), 1.42–1.30 (2 H, OCH₂CH₂),

1

+15.4° (c 0.5, CHCl₃); H NMR (CDCl₃): l 4.99 (dd,

1 H, J_1,2=J_2,39.7 Hz, H-2), 4.35 (d, 1 H, H-1), 4.32

(dd, 1 H, J_5,6a5.9, J_6a,6b11.4 Hz, H-6a), 4.23 (dd, 1 H,

J_5,6b6.7, H-6b), 3.94 (bs, 1 H, OH), 3.70–3.62 (2 H,

H-3, H-5), 3.70 (2 H, H-4, OH), 2.65 (m, 2 H,

SCH₂CH₃), 2.10, 2.07 (s, 3 H, CH₃, acetate), 1.22 (t, 3

2140

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

1.28–0.92 (10 H, CH₂, octyl), 0.88 (t, 3 H, J 7.0 Hz,

CH₃, octyl); ¹³C NMR (CDCl₃): l 139.7, 139.5, 139.4,

133.8 (aromatic quat), 129.1, 128.4, 128.3, 128.2, 128.0,

124.3 (aromatic CH), 101.8 (PhCHO₂), 100.3 (C-1%),

98.1 (C-1), 78.2 (C-2%), 77.0 (C-3), 75.1, 73.1 (PhCH₂),

73.8 (C-5), 72.6 (C-4%), 71.3 (C-3%), 69.8 (OCH₂CH₂),

69.2 (C-2%), 68.8 (C-6%), 68.0 (C-6), 66.1 (C-5%), 55.6

(C-2) 31.5, 29.3, 29.2, 29.1, 25.8, 22.6 (CH₂, octyl), 14.1

(CH₃, octyl). HRESIMS Calcd for C₅₃H₆₁NO₁₄Na

958.3990. Found 958.3997.

CH₃, octyl); ¹³C NMR (CDCl₃): l 138.7, 138.3, 138.1,

137.9, 134.2 (aromatic quat.), 128.9, 128.7, 128.5, 128.4,

128.3, 127.9, 127.6, 127.4, 125.3, 123.4 (aromatic CH),

102.3 (C-1%), 101.1 (PhCHO₂), 97.0 (C-1), 79.4 (C-3%),

78.8 (C-2%), 78.4 (C-4), 76.9 (C-3), 74.3 (C-5), 75.1, 74.7,

72.5 71.6 (PhCH₂), 71.2 (C-4%), 69.2 (OCH₂CH₂), 68.1

(C-6%), 67.5 (C-6), 64.7 (C-5%), 55.0 (C-2) 31.2, 29.9,

29.4, 29.0, 23.6, 22.7 (CH₂, octyl), 14.7 (CH₃, octyl).

Anal. Calcd for C₆₃H₆₉NO₁₂(1031.48): C, 73.31; H,

6.74. Found: C, 73.23; H, 6.61.

Octyl 4,6-O-benzylidene-i-D-galactopyranosyl-(14)-

Octyl 2,3-di-O-benzyl-i-

D-galactopyranosyl (14)-

3,6-di-O-benzyl-2-deoxy-2-phthalimido-i-

D

-glucopy-

3,6-di-O-benzyl-2-deoxy-2-phthalimido-i-

D

-glucopy-

ranoside (41).—Compound 41 (43 mg, 70%) was syn-

thesized from compound 40 (67 mg, 0.072 mmol), and

a catalytic amount of sodium and in MeOH (2 mL) as

ranoside (43).—Compound 42 (549 mg, 0.52 mmol)

was dissolved in 80% AcOH (50 mL). The solution was

heated to 80 °C, stirred for 4 h, cooled to rt and

co-concentrated with toluene. Column chromatography

(5:1 toluene–EtOAc) of the crude resulted in 43 (449

mg, 92%) as a colorless oil: ¹H NMR (CDCl₃): l

7.82–7.60 (4 H, Phth), 7.38–6.82 (20 H, Ph), 5.09 (d, 1

H, J_1,28.6 Hz, H-1), 4.87, 4.84, 4.79, 4.69, 4.46, 4.39 (d,

1 H, J 12.0 Hz, PhCH₂), 4.41 (d, 1 H, J_1%,2%8.4 Hz,

H-1%), 4.28 (dd, 1 H, J_3,48.6, J_2,310.8 Hz, H-3), 4.15

(dd, 1 H, H-2), 4.03 (dd, 1 H, J_4,59.6 Hz, H-4), 3.88 (d,

1 H, J_3%,4%3.0 Hz, H-4%), 3.85 (dd, 1 H, J_5,6a4.0, J_6a,6b

10.8 Hz, H-6a), 3.76 (dt, 1 H, J 6.4, 9.4 Hz,

OCH₂CH₂), 3.74–3.68 (2 H, H-6a%, H-6b), 3.62–3.54 (3

H, H-2%, H-5, H-6b%), 3.38–3.34 (2 H, H-3%,OCH₂CH₂),

3.20 (dd, 1 H, J 4.1, 5.7 Hz, H-5%), 2.60 (bs, 1 H, OH),

2.05 (bs, 1 H, OH), 1.42–1.30 (2 H, OCH₂CH₂), 1.20–

0.90 (10 H, CH₂, octyl), 0.78 (t, 3 H, J 7.0 Hz, CH₃,

octyl); ¹³C NMR (CDCl₃): l 139.3, 139.2, 139.1, 138.6,

134.3 (aromatic quat), 129.2, 129.0, 128.7, 128.6, 128.4,

128.3, 128.2, 127.8, 124.0 (aromatic CH), 103.5 (C-1%),

99.0 (C-1), 81.6 (C-3%), 80.0 (C-2%), 79.2 (C-4), 77.9

(C-3), 76.1, 75.9, 75.4, 74.6, 73.9, 72.9 (C-5, C-5%,

PhCH₂×4), 70.2 (OCH₂CH₂), 68.7 (C-6, C-4%), 68.0

(C-6%), 63.2 (C-2) 32.3, 30.0, 29.8, 29.7, 26.5, 23.3 (CH₂,

octyl), 14.7 (CH₃, octyl). Anal. Calcd for C₅₆H₆₅NO₁₂

(943.45): C, 71.24; H, 6.94. Found: C, 71.02; H, 6.94.

1

described for the preparation of 58: H NMR (CDCl₃):

l 7.80–7.60 (4 H, Phth), 7.32–7.20 (15 H, Ph), 5.44 (s,

1 H, PhCHO₂), 5.01, 4.69, 4.67, 4.53 (d, 1 H, J 11.6 Hz,

PhCH₂), 4.83 (d, 1 H, J_1,27.9 Hz, H-1), 4.49 (d, 1 H,

J_1%,2%7.6 Hz, H-1%), 4.18 (dd, 1 H, J_2,3=J_3,49.0 Hz,

H-3), 4.10 (dd, 1 H, J_6a%,5%1.1, J_6a%,6b%9.3 Hz, H-6a%),

4.04–3.96 (3 H, H-2, H-6a, H-6b), 3.65 (dd, 1 H, J_2%,3%

9.6 Hz, H-2%), 3.55 (ddd, 1 H, J_5,6a=J_5,6b3.0, J_4,511.1

Hz, H-5), 3.32 (1 H, OCH₂CH₂), 3.47–3.40 (2 H, H-3%,

H-6b%), 3.33 (dt, 1 H, J 7.0, 9.4 Hz, OCH₂CH₂), 2.99

(bs, 1 H, H-5%), 1.66–1.45 (2 H, OCH₂CH₂), 1.36–1.20

(10 H, CH₂, octyl), 0.82 (t, 3 H, J 7.0 Hz, CH₃, octyl);

¹³C NMR (CDCl₃): l 139.0, 138.0, 137.7, 134.2 (aro-

matic quat.), 129.2, 128.5, 128.4, 128.3, 128.2, 128.0,

127.8, 127.5, 126.5,123.5 (aromatic CH), 103.4 (C-1%),

101.4 (PhCHO₂), 99.9 (C-1), 79.2, 78.1, 75.3, 75.1, 72.8,

72.3, (C-2%, C-3, C-3%, C-4, C-4%, C-5), 74.7, 73.9

(PhCH₂), 69.7 (OCH₂CH₂), 69.0, 68.8 (C-6, C-6%), 66.9

(C-5%), 57.2 (C-2) 31.8, 29.6, 29.4, 26.0, 23.6, 22.7 (CH₂,

octyl), 14.1 (CH₃, octyl).

Octyl 2,3,-di-O-benzyl-4,6-O-benzylidene-i-

topyranosyl-(14)-3,6,-di-O-benzyl-2-deoxy-2-phthal-

imido-i- -glucopyranoside (42).—Compound 42 (255

D-galac-

D

mg, 66%) was synthesized from compound 41 (320 mg,

0.38 mmol), NaH (44 mg, 60% dispersion in oil, 1.1

mmol), tetrabutyl ammonium iodide (191 mg, 0.52

mmol), benzyl bromide (100 mL, 0.92 mmol) and DMF

(2 mL) as described for the preparation of 59: ¹H NMR

(CDCl₃): l 7.82–7.58 (4 H, Phth), 7.20–6.75 (25 H,

Ph), 5.40 (s, 1 H, PhCHO₂), 5.09 (d, 1 H, J_1,28.6 Hz,

H-1), 5.03, 4.86, 4.83, 4.72, 4.62, 4.59, 4.34 (d, 1 H, J

12.7 Hz, PhCH₂), 4.47 (d, 1 H, J_1%,2%7.6 Hz, H-1%), 4.28

(dd, 1 H, J_3,48.4, J_2,310.7 Hz, H-3), 4.26 (dd, 1 H, J_6a%,5%

1.2, J_6a%,6b%12.2 Hz, H-6a%), 4.17 (dd, 1 H, H-2), 4.08

(dd, 1 H, J_4,58.5 Hz, H-4), 4.01 (d, 1 H, J_3%,4%3.7 Hz,

H-4%), 3.91 (dd, 1 H, J_5,6a3.8, J_6a,6b12.0 Hz, H-6a), 3.85

(dd, 1 H, J_5,6b1.7 Hz, H-6b), 3.80–3.69 (3 H, H-2%,

H-6b%, OCH₂CH₂), 3.53 (1 H, H-5), 3.40 (dd, 1 H, J_2%,3%

9.6 Hz, H-3%), 3.32 (dt, 1 H, J 6.1, 9.3 Hz, OCH₂CH₂),

3.14 (bs, 1 H, H-5%), 1.40–1.25 (2 H, OCH₂CH₂),

1.15–0.90 (10 H, CH₂, octyl), 0.78 (t, 3 H, J 7.0 Hz,

Octyl 2,3-di-O-benzyl-6-O-trityl-i-

osyl - (14) - 3,6 - di - O - benzyl - 2 - deoxy - 2 - phthal-

imido-i- -glucopyranoside (44).—Compound 43 (428

D-galactopyran-

D

mg, 0.45 mmol) was dissolved in dry DCM (15 mL),

and trityl chloride (184 mg, 0.65 mmol) and diisopropy-

lethylamine (115 mL, 0.64 mmol) were added. The

solution was stirred at rt for 8 h, diluted with toluene

and concentrated under reduced pressure. Column

chromatography (10:1 toluene–EtOAc) of the crude

material afforded 44 (556 mg, quant): ¹H NMR

(CDCl₃): l 7.80–7.60 (4 H, Phth), 7.40–6.85 (35 H,

Ph), 5.07 (d, 1 H, J_1,28.2 Hz, H-1), 4.82, 4.79, 4.74,

4,71, 4.68, 4.60, 4.46, 4.40 (d, 1 H, J 12.2 Hz, PhCH₂),

4.38 (d, 1 H, J_1%,2%7.9 Hz, H-1%), 4.21 (dd, 1 H, J_3,48.3,

J_2,310.7 Hz, H-3), 4.16 (dd, 1 H, H-2), 4.09 (dd, 1 H,

J_4,59.9 Hz, H-4), 3.97 (d, 1 H, J_3%,4%2.9 Hz, H-4%), 3.86

(dd, 1 H, J_5,6a4.0, J_6a,6b11.0 Hz, H-6a), 3.75 (dt, 1 H,

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2141

J 6.4, 9.2 Hz, OCH₂CH₂), 3.71 (dd, 1 H, J_5,6b1.5,

H-6b), 3.64 (dd, 1 H, J_2%,3%9.3 Hz, H-2%), 3.51 (ddd, 1 H,

J_5,49.9 Hz, H-5), 3.42 (dd, 1 H, J_5%6a%6.4, J_6a%,6b%9.6 Hz,

H-6a%), 3.33 (dt, 1 H, J 6.2, 9.0 Hz, OCH₂CH₂), 3.31

(dd, 1 H, J_2%,3%9.3 Hz, H-3%), 3.21 (dd, 1 H, J_5%,6b%4.6,

H-6b%), 3.09 (dd, 1 H, H-5%), 2.60 (bs, 1 H, OH),

1.40–1.30 (2 H, OCH₂CH₂), 1.25–0.90 (10 H, CH₂,

octyl), 0.80 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C NMR

(CDCl₃): l 144.7, 139.4, 139.3, 139.1, 138.9, 134.3

(aromatic quat), 129.7, 129.4, 129.1, 129.0, 128.9, 128.8,

128.6, 128.5, 128.4, 128.3, 128.2, 127.8, 127.5, 123.8

(aromatic CH), 103.4 (C-1%), 99.1 (C-1), 87.6 (Ph₃C),

81.7 (C-3%), 80.3 (C-2%), 78.4 (C-4), 77.7 (C-3), 76.0

(C-5), 73.3 (C-5%), 76.1, 74.9, 73.9, 72.7 (PhCH₂), 70.2

(OCH₂CH₂), 68.7 (C-6), 67.9 (C-4%), 63.5 (C-6%), 56.2

(C-2) 32.3, 30.0, 29.9, 29.8, 26.5, 23.3 (CH₂, octyl), 14.7

(CH₃, octyl).

colorless oil: ¹H NMR (CDCl₃): l 7.80–7.60 (4H,

Phth), 7.38–6.85 (25 H, Ph), 5.08 (d, 1 H, J_1,28.4 Hz,

H-1), 4.89, 4.88, 4.84, 4,82, 4.56, 4.52, 4.45, 4.38 (d, 1

H, J 11.9 Hz, PhCH₂), 4.41 (d, 1 H, J_1%,2%8.5 Hz, H-1%),

4.28 (dd, 1 H, J_3,49.3, J_2,310.8 Hz, H-3), 4.14 (dd, 1 H,

H-2), 3.98 (dd, 1 H, J_4,58.9 Hz, H-4), 3.84 (dd, 1 H,

J_5,6a4.2, J_6a,6b10.8 Hz, H-6a), 3.78–3.72 (3 H, H-2%,

H-6b, OCH₂CH₂), 3.66 (d, 1 H, J_3%,4%3.9 Hz, H-4%),

3.58–3.52 (2 H, H-5, H-6a%), 3.39 (dd, 1 H, J_2%,3%9.3 Hz,

H-3%), 3.34 (dt, 1 H, J 6.1, 9.5 Hz, OCH₂CH₂), 3.29 (dd,

1 H, J_5%,6b%4.5, J_6a%,6b%12.0 Hz, H-6b%), 3.20 (dd, 1 H,

J_5%,6a%7.7 Hz, H-5%), 2.34 (bs, 1 H, OH), 1.40–1.20 (2 H,

OCH₂CH₂), 1.15–0.92 (10 H, CH₂, octyl), 0.80 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 138.8,

138.7, 138.6, 138.5, 133.7 (aromatic quat), 131.8, 128.5,

128.3, 127.9, 127.6, 127.5, 127.0, 123.2 (aromatic CH),

103.1 (C-1%), 98.4 (C-1), 82.6 (C-3%), 80.0 (C-2%), 78.6

(C-4), 77.3 (C-3), 75.4 (C-5), 75.3, 74.9, 74.7, 74.3, 73.8,

73.2, 73.1 (C-4%, C-5%, PhCH₂×5), 69.5 (OCH₂CH₂),

68.1 (C-6), 62.0 (C-6%), 55.9 (C-2) 31.7, 29.3, 29.2, 29.1,

25.9, 22.6 (CH₂, octyl), 14.7 (CH₃, octyl). Anal. Calcd

for C₆₃H₇₁NO₁₂(1034.24): C, 73.16; H, 6.92. Found: C,

72.90; H, 6.85.

Octyl

ranosyl - (14) - 3,6 - di - O - benzyl - 2 - deoxy - 2 - phthal-

imido-i- -glucopyranoside (45).—Compound 45 (477

2,3,4-tri-O-benzyl-6-O-trityl-i-D-galactopy-

D

mg, 84%) was synthesized from 44 (521 mg, 0.45

mmol), NaH (31mg, 60% dispersion in oil, 0.68 mmol),

benzyl bromide (150 mL, 1.35 mmol), tetra-

butylammonium iodide (550 mg, 1.35 mmol) and DMF

Octyl 2,3,4-tri-O-benzyl-i-

D-galactopyranosyl-(1

1

(5 ml) as described for the preparation of 60: H NMR

4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-i-

D

-gluco-

(CDCl₃): l 7.80–7.60 (4 H, Phth), 7.38–6.70 (40 H,

Ph), 5.02 (d, 1 H, J_1,28.6 Hz, H-1), 4.84, 4.78, 4.75,

4,70, 4.69, 4.58, 4.43, 4.41, 4.37 (d, 1 H, J 11.5 Hz,

PhCH₂), 4.36 (d, 1 H, J_1%,2%7.7 Hz, H-1%), 4.20 (dd, 1 H,

J_3,48.3, J_2,310.8 Hz, H-3), 4.11 (dd, 1 H, H-2), 3.98

(dd, 1 H, J_4,59.9 Hz, H-4), 3.96 (d, 1 H, J_3%,4%2.9 Hz,

H-4%), 3.84 (dd, 1 H, J_5,6a4.2, J_6a,6b10.8 Hz, H-6a),

3.75–3.68 (3 H, H-2%, H-6b, OCH₂CH₂), 3.49 (ddd, 1

H, J_5,6b1.9 Hz, H-5), 3.37–3.30 (3 H, H-3%, H-6a%,

OCH₂CH₂), 3.21 (dd, 1 H, J_5%,6b%=J_6a%,6b%9.1 Hz, H-

6b%), 3.11 (dd, 1 H, J_5%,6a%5.9 Hz, H-5%), 1.40–1.25 (2 H,

OCH₂CH₂), 1.08–0.92 (10 H, CH₂, octyl), 0.80 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 144.9,

139.9, 139.6, 139.4, 139.3, 139.2, 134.2 (aromatic quat.),

129.3, 129.1, 129.0, 128.9, 128.6, 128.5, 128.4, 128.3,

128.2, 128.1, 127.8, 127.7, 127.6, 123.4 (aromatic CH),

103.6 (C-1%), 99.0 (C-1), 87.5 (Ph₃C), 83.0 (C-3%), 80.9

(C-2%), 78.6 (C-4), 78.6 (C-3), 77.9 (C-5), 76.1, 74.9,

74.7, 74.5 (PhCH₂), 74.8 (C-4%), 73.9 (C-5%), 73.8, 70.1

(OCH₂CH₂), 68.8 (C-6), 62.4 (C-6%), 56.4 (C-2) 32.3,

30.0, 29.9, 29.8, 26.5, 23.3 (CH₂, octyl), 14.7 (CH₃,

octyl). Anal. Calcd for C₈₂H₈₅NO₁₂(1276.55): C, 77.15;

H, 6.71. Found: C, 76.92; H, 6.84.

pyranoside (47).—Compound 47 (255 mg, 86%) was

synthesized from compound 46 (311 mg, 0.30 mmol),

tert-butanol (15 mL) and ethylenediamine (5 mL), fol-

lowed by Ac₂O (4 mL), MeOH (10 mL) and triethy-

lamine (0.1 mL) as described for the preparation of 61:

¹H NMR (CDCl₃): l 7.38–7.20 (25 H, Ph), 5.65 (d, 1

H, J 7.7 Hz, NHAc), 4.98, 4.92, 4.82, 4.79, 4.74, 4.72,

4.58, 4.56, 4.53, 4.41 (d, 1 H, J 11.2 Hz, PhCH₂), 4.90

(d, 1 H, J_1,27.3 Hz, H-1), 4.39 (d, 1 H, J_1%,2%7.9 Hz,

H-1%), 4.17 (dd, 1 H, J_2,3=J_3,48.8 Hz, H-3), 3.89 (dd, 1

H, J_4,58.2 Hz, H-4), 3.83–3.74 (4 H, H-2%, H-6a, H-6b,

OCH₂CH₂), 3.70 (d, 1 H, J_3%,4%2.7 Hz, H-4%), 3.62 (ddd,

1 H, J 3.3, 7.9 Hz, H-5), 3.58 (dd, 1 H, J 3.5, 7.7,

H-6a%), 3.44 (dt, 1 H, J 6.2, 9.0 Hz, OCH₂CH₂), 3.39

(dd, 1 H, J_2%,3%10.7 Hz, H-3%), 3.35 (m, 1 H, H-6b%), 3.29

(ddd, 1 H, H-2), 3.19 (dd, 1 H, J 5.1, 8.5 Hz, H-5%), 2.40

(bs, 1 H, OH), 1.84 (s, 3 H, CH₃NHAc), 1.62–1.45 (2

H, OCH₂CH₂), 1.35–1.20 (10 H, CH₂, octyl), 0.84 (t, 3

H, J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 171.0

(CO, acetate), 139.6, 139.3, 139.2, 139.1, 139.0 (aro-

matic quat), 129.1, 129.0, 128.9, 128.8, 128.6, 128.4,

128.2, 128.1 (aromatic CH), 103.9 (C-1%), 100.2 (C-1),

83.2 (C-3%), 80.6 (C-2%), 78.2 (C-4), 78.1 (C-3), 76.0,

75.7, 75.5, 75.1, 74.4, 73.9, 73.8, (C-4%, C-5, C-5%,

PhCH₂×5), 70.3 (OCH₂CH₂), 69.4 (C-6), 62.5 (C-6%),

57.1 (C-2) 32.5, 30.3, 30.1, 30.0, 26.7, 24.3 (CH₂, octyl),

23.3 (CH₃, acetate), 14.7 (CH₃, octyl). Anal. Calcd for

C₅₇H₇₁NO₁₁(945.17): C, 72.36; H, 7.56. Found: C,

72.16; H, 7.71.

Octyl 2,3,4-tri-O-benzyl-i-

D-galactopyranosyl-(1

4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-i-

D

-gluco-

pyranoside (46).—Compound 45 (456 mg, 0.36 mmol)

was dissolved in a solution of 5% triﬂuoroacetic acid

and 5% triisopropylsilane in DCM (20 mL). The reac-

tion mixture was stirred at rt for 2 h and concentrated

with toluene as a co-solvent. Column chromatography

(7:1 toluene–EtOAc) resulted in 46 (330 mg, 97%) as a

Octyl 2,3,6-tri-O-benzyl-i-

D-galactopyranosyl-(1

4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-i-

D

-gluco-

2142

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

pyranoside (48).—Compound 42 (214 mg, 0.21 mmol),

sodium cyanoborohydride (64 mg, 1.01 mmol), and

methyl orange indicator were dissolved in dry THF (5

127.4, 127.1, 125.3 (aromatic CH), 102.5 (C-1%), 99.1

(C-1), 81.3 (C-3%), 78.7 (C-2%), 77.3 (C-3), 76.4 (C-4),

74.9, 73.8, 73.1, 72.2, 71.8 (PhCH₂), 74.0 (C-5), 72.1

(C-5%), 69.0 (OCH₂CH₂), 62.9, 62.8 (C-6, C-6%), 65.2

(C-4%), 54.7 (C-2) 34.8, 32.8, 32.7, 28.9, 22.3 (CH₂,

octyl), 23.3 (CH₃, acetate), 14.7 (CH₃, octyl). Anal.

Calcd for C₅₇H₇₁NO₁₁(945.17): C, 72.36; H, 7.56.

Found: C, 71.87; H, 7.58.

,

mL) containing crushed 4 A molecular sieves. The

solution was cooled to 0 °C, followed by the addition of

ethereal hydrogen chloride until the red color of the

solution persisted. After 3 h the reaction was quenched

with sodium bicarbonate, ﬁltered through Celite, di-

luted with DCM, washed with water and concentrated

under reduced pressure. Column chromatography (7:1

toluene–EtOAc) of the residue gave 48 (124 mg, 57%)

Octyl 2,4,6-tri-O-acetyl-3-O-allyl-i-

osyl-(14)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-i-

-glucopyranoside (50).—Compound 50 (447 mg, 81%)

was synthesized from octyl 3,6-di-O-benzyl-2-deoxy-2-

phthalimido-b-

-glucopyranoside (38)⁶(343 mg, 0.64

D-galactopyran-

D

1

as a colorless oil: H NMR (CDCl₃): l 7.80–7.60 (4 H,

Phth), 7.38–6.80 (25 H, Ph), 5.07 (d, 1 H, J_1,28.4 Hz,

H-1), 4.83, 4.82, 4.78, 4,70, 4.66, 4.57, 4.46, 4.42, 4.37

(d, 1 H, J 12.1 Hz, PhCH₂), 4.41 (d, 1 H, J_1%,2%8.0 Hz,

H-1%), 4.26 (dd, 1 H, J_3,48.6, J_2,310.9 Hz, H-3), 4.15

(dd, 1 H, H-2), 4.04 (dd, 1 H, J_4,58.7 Hz, H-4), 3.99 (s,

1 H, H-4%), 3.85 (dd, 1 H, J_5,6a4.1, J_6a,6b11.0 Hz, H-6a),

3.75 (dt, 1 H, J 6.0, 9.5 Hz, OCH₂CH₂), 3.71 (dd, 1 H,

J_5,6b1.2 Hz, H-6b), 3.65 (dd, 1 H, J_5%,6a%6.8, J_6a%,6b%10.0

Hz, H-6a%), 3.60 (dd, 1 H, J_2%,3%7.9 Hz, H-2%), 3.56–3.50

(2 H, H-5, H-6b%), 3.37–3.30 (3 H, H-3%, H-5%,

OCH₂CH₂), 1.40–1.30 (2 H, OCH₂CH₂), 1.18–0.88 (10

H, CH₂, octyl), 0.78 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 139.6, 139.3, 139.1, 138.8, 138.7,

134.3 (aromatic quat.), 132.4, 129.2, 129.1, 129.0, 128.9,

128.7, 128.6, 128.5, 128.4, 128.3, 128.1, 127.6 (aromatic

CH), 103.9 (C-1%), 99.0 (C-1), 81.7 (C-3%), 80.1 (C-2%),

78.9 (C-4), 77.8 (C-3), 76.1, 75.1, 74.3, 73.8, 73.5

(PhCH₂), 75.0 (C-5), 72.8 (C-5%), 70.2 (OCH₂CH₂), 69.5

(C-6%), 68.7 (C-6), 67.2 (C-4%), 56.5 (C-2) 32.3, 30.0,

29.9, 29.8, 26.5, 23.3 (CH₂, octyl), 14.7 (CH₃, octyl).

Anal. Calcd for C₆₃H₇₁NO₁₂(1034.24): C, 73.16; H,

6.92. Found: C, 73.32; H, 6.87.

D

mmol), donor 37 (381 mg, 0.98 mmol), N-iodosuccin-

imide (247 mg, 0.99 mmol), a catalytic amount of silver

triﬂate, and dry DCM (20 mL) as described for com-

1

pound 57: H NMR (CDCl₃): l 7.80–7.60 (4 H, Phth),

7.38–6.80 (10 H, Ph), 5.76 (1 H, OCH₂CHꢀCH₂), 5.28

(dd, 1 H, J_4%,5%1.1, J_3%,4%3.3 Hz, H-4%), 5.22 (1 H, J_cis10.5

Hz, OCH₂CHꢀCHH), 5.15 (1 H, J_trans17.0 Hz,

OCH₂CHꢀCHH), 5.05 (d, 1 H, J_1,28.6 Hz, H-1), 5.03

(dd, 1 H, J_1%,2%8.1, J_2%,3%10.0 Hz, H-2%), 4.79, 4.77, 4.50,

4.42 (d, 1 H, J 12.3 Hz, PhCH₂), 4.54 (d, 1 H, H-1%),

4.22 (dd, 1 H, J_3,48.6, J_2,310.9 Hz, H-3), 4.10 (dd, 1 H,

H-2), 4.08 (1 H, OCHHCHꢀCH₂), 4.00 (dd, 1 H, J_4,5

9.9 Hz, H-4), 3.94 (dd, 1 H, J_5%,6a%1.7, J_6a%,6b%6.7 Hz,

H-6a%), 3.84 (1 H, OCHHCHꢀCH₂), 3.79–3.76 (3 H,

H-6a, H-6b, H-6b%), 3.73 (dt, 1 H, J 6.4, 9.5 Hz,

OCH₂CH₂), 3.56 (ddd, 1 H, J_4%,5%1.2, J_5%,6b%5.5 Hz,

H-5%), 3.52 (1 H, H-5), 3.32 (dt, 1 H, J 6.2, 9.4 Hz,

OCH₂CH₂), 3.27 (dd, 1 H, H-3%), 2.02 (s, 9 H, CH₃,

acetate), 1.42–1.34 (2 H, OCH₂CH₂), 1.18–0.90 (10 H,

CH₂, octyl), 0.78 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 170.5, 170.3, 169.3 (CO, acetate),

138.8, 138.3 (aromatic quat.), 134.2 (CH₂ꢀCHCH₂O),

128.5, 128.0, 127.9, 127.8, 127.0, 123.2 (aromatic CH),

117.1 (CH₂ꢀCHCH₂O), 100.6 (C-1%), 98.4 (C-1), 78.3

(C-4), 77.0 76.9 (C-3, C-3%), 75.0 (C-5), 74.4, 73.6

Octyl 2,3,6-tri-O-benzyl-i-

D-galactopyranosyl-(1

4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-i-

D

-gluco-

pyranoside (49).—Compound 49 (91 mg, 90%) was

synthesized from compound 48 (110 mg, 0.11 mmol),

tert-butanol (5 mL) and ethylenediamine (2 mL), fol-

lowed by Ac₂O (2 mL), MeOH (5 mL) and triethy-

lamine (0.1 mL) as described for the preparation of 61:

¹H NMR (CDCl₃): l 7.35–7.20 (25 H, Ph), 5.68 (s, 1 H

NHAc), 4.89 (d, 1 H, J_1,27.0 Hz, H-1), 4.88, 4.81, 4.74,

4,70, 4.66, 4.58, 4.54, 4.47, 4.43, 4.37 (d, 1 H, J 11.3 Hz,

PhCH₂), 4.41 (d, 1 H, J_1%,2%7.8 Hz, H-1%), 4.12 (dd, 1 H,

(PhCH₂),

71.1

(C-2%),

70.7

(C-5%),

70.5

(CH₂ꢀCHCH₂O), 69.6 (OCH₂CH₂), 67.9 (C-6), 65.9

(C-4%), 61.4 (C-6%), 55.8 (C-2) 31.7, 29.2, 29.1, 25.8, 22.6

(CH₂, octyl), 21.0, 20.8 (CH₃, acetate), 14.7 (CH₃,

octyl). HRESIMS Calcd for C₅₁H₆₃NO₁₅Na 952.4095.

Found 952.4094.

Octyl 3-O-allyl-2,4,6-tri-O-benzyl-i-

osyl-(14)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-i-

-glucopyranoside (51).—Compound 51 (142 mg, 27%)

D-galactopyran-

J_2,3=J_3,48.4 Hz, H-3), 4.00 (d, 1 H, J_3%,4%3.5 Hz, H-4%),

3.96 (dd, 1 H, J_4,57.8 Hz, H-4), 3.83–3.78 (2 H, H-6a,

OCH₂CH₂), 3.73 (dd, 1 H, J_5%,6a%3.0, J_6a%,6b%10.6 Hz,

H-6a%), 3.68 (dd, 1 H, J_5,6b6.8, J_6a,6b9.7 Hz, H-6b),

3.61–3.56 (2 H, H-2%, H-5), 3.53 (dd, 1 H, J_5%,6b%5.3 Hz,

H-6b%), 3.43 (dt, 1 H, J 6.4, 9.1 Hz, OCH₂CH₂), 3.38–

3.30 (3 H, H-2, H-3%, H-5%), 2.42 (bs, 1 H, OH), 1.84 (s,

3 H, CH₃, acetate), 1.60–1.48 (2 H, OCH₂CH₂), 1.35–

1.20 (10 H, CH₂, octyl), 0.85 (t, 3 H, J 7.0 Hz, CH₃,

octyl); ¹³C NMR (CDCl₃): l 139.2, 139.1, 138.3, 138.2,

138.0 (aromatic quat), 128.9, 128.7, 128.6, 128.4, 128.3,

D

was synthesized through an initial deacetylation of 50

(446 mg, 0.52 mmol) with sodium and MeOH as de-

scribed for compound 58. The crude was redissolved in

DMF (5 mL) with NaH (32 mg, 60% dispersion in oil,

0.80 mmol), tetrabutylammonium iodide (87 mg, 2.4

mmol) and benzyl bromide (250 mL, 2.3 mmol) as

1

described for the preparation of 59: H NMR (CDCl₃):

l 7.80–7.60 (4 H, Phth), 7.38–6.80 (25 H, Ph),

5.91 (1 H, OCH₂CHꢀCH₂), 5.31 (1 H, J_cis10.5 Hz,

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2143

OCH₂CHꢀCHH), 5.15 (1 H, J_trans17.0 Hz,

OCH₂CHꢀCHH), 5.08 (d, 1 H, J_1,28.4 Hz, H-1), 4.91,

4.86, 4.80, 4.76, 4.55, 4.50, 4.34 (d, 1 H, J 11.7 Hz,

PhCH₂), 4.45–4.38 (4 H, H-1%, PhCH₂×3), 4.27–4.22

(3 H, H-3, H-6a, PhCH₂), 4.27–4.13 (2 H, H-2, OCH-

HCHꢀCH₂), 4.00 (dd, 1 H, J_3,48.6, J_4,510.0 Hz, H-4),

3.82–3.66 (6 H, H-2%, H-4%, H-6a%, H-6b, OCH₂CH₂,

OCHHCHꢀCH₂), 3.54 (ddd, 1 H, J 1.6, 2.2, 11.5 Hz,

H-5), 3.44–3.38 (2 H, H-5%, H-6b%), 3.36 (dt, 1 H, J 6.5,

9.5 Hz, OCH₂CH₂), 3.28 (dd, 1 H, J_3%,4%3.1, J_2%,3%9.7 Hz,

H-3%), 1.40–1.30 (2 H, OCH₂CH₂), 1.24–0.90 (10 H,

CH₂, octyl), 0.78 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 139.2, 139.1, 138.9, 138.5, 138.1,

133.3 (aromatic quat.), 135.0 (CH₂ꢀCHCH₂O), 128.4,

128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6,

127.5, 127.4, 127.3, 126.8 (aromatic CH), 116.5

(CH₂ꢀCHCH₂O), 103.0 (C-1%), 98.4 (C-1), 82.2 (C-3%),

80.0 (C-5%),78.2 (C-2%), 77.5 (C-4), 77.3 (C-3), 75.4 (C-5),

lowed by Ac₂O (4 mL), MeOH (10 mL) and triethy-

lamine (0.2 mL) as described for the preparation of 61:

¹H NMR (CDCl₃): l 7.35–7.20 (25 H, Ph), 5.70 (d, 1

H, J 7.5 Hz, NHAc), 4.91 (d, 1 H, J_1,27.4 Hz, H-1),

4.85, 4.83, 4.76, 4.57, 4.56, 4.54, 4.42, 4.38, 4.30 (d, 1 H,

J 11.6 Hz, PhCH₂), 4.14 (d, 1 H, J_1%,2%7.3 Hz, H-1%),

4.14 (dd, 1 H, J_2,3=J_3,48.8 Hz, H-3), 3.94 (dd, 1 H, J_4,5

8.0 Hz, H-4), 3.83 (d, 1 H, J_3%,4%2.8 Hz, H-4%), 3.81–3.74

(3 H, H-6a, H-6b, OCH₂CH₂), 3.60 (ddd, 1 H, J_5,6a

=

J_5,6b3.3 Hz, H-5), 3.54 (dd, 1 H, J_5%,6a%=J_5%,6b%6.4 Hz,

H-5%), 3.52–3.40 (5 H, H-2%, H-3%, H-6a%, H-6b%,

OCH₂CH₂), 3.31 (ddd, 1 H, H-2), 2.18 (bs, 1 H, OH),

1.92 (s, 3 H, CH₃, acetate), 1.60–1.50 (2 H, OCH₂CH₂),

1.34–1.20 (10 H, CH₂, octyl), 0.84 (t, 3 H, J 7.0 Hz,

CH₃, octyl); ¹³C NMR (CDCl₃): l 170.9 (CO, acetate),

139.7, 139.7, 139.1, 139.0, 138.6 (aromatic quat.), 129.2,

129.1, 129.0, 128.9, 128.7, 128.5, 128.4, 128.3, 128.2,

128.1 (aromatic CH), 103.7 (C-1%), 100.1 (C-1), 81.4

(C-3%), 78.1 (C-3), 77.8 (C-4), 76.5 (C-4%), 75.9 (C-5),

75.8, 75.7, 75.6, 74.7, 74.1, 74.0, 73.9 (C-2%, C-5%,

PhCH₂×5), 70.4 (OCH₂CH₂), 69.3, 68.8 (C-6, C-6%),

57.0 (C-2) 32.4, 32.0, 30.1, 30.0, 26.7, 24.3 (CH₂, octyl),

23.4 (CH₃, acetate), 14.8 (CH₃, octyl). Anal. Calcd for

C₅₇H₇₁NO₁₁(945.17): C, 72.36; H, 7.56. Found: C,

72.37; H, 7.69.

74.5,

74.4,

73.5,

73.3,

73.1

(PhCH₂×5,

CH₂ꢀCHCH₂O), 69.5 (OCH₂CH₂), 68.3, 68.2 (C-4%,

C-6, C-6%), 55.8 (C-2) 31.7, 29.3, 29.2, 29.1, 25.9, 22.6

(CH₂, octyl), 14.1 (CH₃, octyl). Anal. Calcd for

C₆₆H₇₅NO₁₂(1074.30): C, 73.79; H, 7.04. Found: C,

73.43; H, 6.74.

Octyl 2,4,6-tri-O-benzyl-i-

D-galactopyranosyl-(1

Octyl 2-O-acetyl-3,4,6-tri-O-benzyl-i-

ranosyl - (14) - 3,6 - di - O - benzyl - 2 - deoxy - 2 - phthal-

imido-i- -glucopyranoside (55).—Compound 55 (1.38

g, 81% based on the acceptor) was synthesized

from octyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-b-

glucopyranoside (38)⁶(965 mg, 1.6 mmol), ethyl 2-O-

-galactopyranoside⁹

D-galactopy-

4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-i-

D

-gluco-

pyranoside (52).—Compound 52 (204 mg, 88%) was

synthesized from compound 51 (241 mg, 0.25 mmol),

palladium chloride (6 mg, 0.026 mmol), and MeOH (5

D

D-

1

mL) as described for the preparation of 65: H NMR

(CDCl₃): l 7.80–7.60 (4 H, Phth), 7.38–6.80 (25 H,

Ph), 5.09 (d, 1 H, J_1,28.5 Hz, H-1), 4.86, 4.72, 4.68,

4.59, 4.56 (d, 1 H, J 11.8 Hz, PhCH₂), 4.48–4.36 (4 H,

H-1%, PhCH₂×3), 4.30–4.24 (2 H, H-3, PhCH₂), 4.17

(dd, 1 H, J_2,310.9 Hz, H-2), 3.84 (dd, 1 H, J_3,4=J_4,58.7

Hz, H-4), 3.84 (dd, 1 H, J_5,6a4.1, J_6a,6b11.0 Hz, H-6a),

3.81 (d, 1 H, J_3%,4%2.2 Hz, H-4%), 3.78–3.73 (2 H, H-6b,

OCH₂CH₂), 3.56 (m, 1 H, H-5), 3.51–3.42 (5 H, H-2%,

H-3%, H-5%, H-6a%, H-6b%), 3.35 (dt, 1 H, J 6.2, 9.0 Hz,

OCH₂CH₂), 2.16 (bs, 1 H, OH), 1.50–1.40 (2 H,

OCH₂CH₂), 1.34–0.90 (10 H, CH₂, octyl), 0.80 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 139.7,

139.4, 139.1, 139.0, 138.7, 134.4 (aromatic quat.), 132.4,

129.2, 129.1, 129.0, 128.7, 128.5, 128.4, 128.3, 128.2,

127.5 (aromatic CH), 103.7 (C-1%), 99.1 (C-1), 81.4

(C-3%), 78.9 (C-4),77.2 (C-3), 76.6 (C-4%), 77.3 (C-3), 76.0

(C-5), 75.8, 75.6, 75.0, 74.7, 74.1, 74.0, 73.9 (C-2%, C-5%,

PhCH₂×5), 70.2 (OCH₂CH₂), 68.8 (C-6, C-6%), 56.5

(C-2) 32.4, 32.0, 29.9, 29.8, 25.5, 23.3 (CH₂, octyl), 14.7

(CH₃, octyl). HRESIMS Calcd for C₆₃H₇₁NO₁₂Na

1056.4874. Found 1056.4868.

acetyl-2,4,6-tri-O-benzyl-thio-b-

D

(54, 1.65 g, 3.1 mmol), N-iodosuccinimide (765 mg, 3.1

mmol), a catalytic amount of silver triﬂate and dry

,

DCM (30 mL) containing crushed 4 A molecular sieves

as described for the preparation of 57: ¹H NMR

(CDCl₃): l 7.80–7.60 (4 H, Phth), 7.38–6.78 (25 H,

Ph), 5.34 (dd, 1 H, J_1%,2%8.0, J_2%,3%10.1 Hz, H-2%), 5.06 (d,

1 H, J_1,28.4 Hz, H-1), 5.06, 4.90, 4.84, 4.73, 4.63, 4.49,

4.45, 4.41, 4.33, 4.25 (d, 1 H, J 12.1 Hz, PhCH₂), 4.47

(d, 1 H, H-1%), 4.24 (dd, 1 H, J_2,3=J_3,48.7 Hz, H-3),

4.13 (dd, 1 H, H-2), 3.97 (d, 1 H, J_3%,4%3.9 Hz, H-4%),

3.78–3.73 (3 H, H-6a, H-6b, OCH₂CH₂), 3.52 (ddd, 1

H, J_5,6a=J_5,6b3.1, J_4,59.9 Hz, H-5), 3.48–3.37 (4 H,

H-5%, H-6a%,H-6b%, OCH₂CH₂), 3.34 (dd, 1 H, H-3%),

1.98 (s, 3 H, CH₃, acetate), 1.42–1.36 (2 H, OCH₂CH₂),

1.10–0.90 (10 H, CH₂, octyl), 0.78 (t, 3 H, J 7.0 Hz,

CH₃, octyl); ¹³C NMR (CDCl₃): l 170.0 (CO, acetate),

139.6, 139.5, 138.9, 138.8, 138.7 (aromatic quat.), 134.3,

129.1, 128.8, 128.6, 128.5, 128.0, 127.4 (aromatic CH),

101.5 (C-1%), 99.1 (C-1), 80.4 (C-3%), 78.0 (C-4), 77.1

(C-3), 75.1 (C-5), 74.6, 74.4, 73.5, 73.4 (PhCH₂), 73.3

(C-5%), 72.7 (C-4%), 71.7 (C-2%), 69.6 (OCH₂CH₂), 68.1,

68.0 (C-6, C-6%), 55.8 (C-2) 31.6, 29.3, 29.1, 25.8, 22.6

(CH₂, octyl), 21.1 (CH₃, acetate), 14.1 (CH₃, octyl).

Anal. Calcd for C₆₅H₇₃NO₁₃(1076.27): C, 72.54; H,

6.84. Found: C, 72.91; H, 6.86.

Octyl 2,4,6-tri-O-benzyl-i-

D-galactopyranosyl-(1

4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-i-

D

-gluco-

pyranoside (53).—Compound 53 (162 mg, 94%) was

synthesized from compound 52 (191 mg, 0.18 mmol),

tert-butanol (10 mL) and ethylenediamine (4 mL) fol-

2144

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

Octyl 3,4,6-tri-O-benzyl-i-

4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-i-

D

-galactopyranosyl-(1

CH₂, octyl), 0.80 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 169.3 (CO, acetate), 159.2 (CO,

Phth), 139.0, 138.8, 138.2, 138.0, 130.4 (aromatic quat),

133.7, 129.5, 128.4, 128.1, 127.8, 127.7, 127.6, 127.3,

127.2, 126.7, 123.2, 113.8 (aromatic CH), 100.9 (C-1%),

98.4 (C-1), 80.6 (C-3%), 78.0 (C-4), 77.1 (C-3), 75.2

(C-5), 74.5, 74.4, 73.4, 73.3, 71.8 (PhCH₂), 73.3 (C-5%),

72.8 (C-4%), 72.0 (C-2%), 69.6 (OCH₂CH₂), 68.1 (C-6%),

67.6 (C-6%), 55.9 (C-2), 55.3 (OCH₃), 31.7, 29.3, 29.2,

29.1, 25.9, 22.6 (CH₂, octyl), 21.1 (CH₃, acetate), 14.1

(CH₃, octyl). Anal. Calcd for C₆₆H₇₅NO₁₄(1106.30): C,

71.65; H, 6.83. Found: C, 71.42; H, 6.84.

D

-gluco-

pyranoside (56).—Compound 56 (1.10 g, 92%) was

synthesized from compound 55 (1.37 g, 1.23 mmol),

tert-butanol (50 mL), ethylenediamine (20 mL) fol-

lowed by Ac₂O (10 mL), MeOH (40 mL) and triethy-

lamine (0.5 mL) as described for the preparation of 61:

¹H NMR (CDCl₃): l 7.18–7.10 (25 H, Ph), 5.69 (d, 1

H, J 7.7 Hz, NHAc), 4.87, 4.69, 4.64, 4.62, 4.59, 4.53,

4.51, 4.33, 4.26 (d, 1 H, J 12.1 Hz, PhCH₂), 4.77 (d, 1

H, J_1,27.5 Hz, H-1), 4.48 (d, 1 H, J_1%,2%7.6 Hz, H-1%),

4.09 (dd, 1 H, J_2,3=J_3,48.7 Hz, H-3), 3.98 (dd, 1 H, J_4,5

8.3 Hz, H-4), 3.95–3.87 (2 H, H-2%, H-6a), 3.86 (d, 1 H,

J_3%,4%2.5 Hz, H-4%), 3.83–3.76 (2 H, H-6b, OCH₂CH₂),

3.59 (ddd, 1 H, J_5,6a=J_5,6b3.1, H-5), 3.53 (d, 1 H,

J_5%,6a%=J_6a%,6b%7.5 Hz, H-6a%), 3.44–3.32 (4 H, H-2, H-5%,

H-6b%, OCH₂CH₂), 3.34 (dd, J_2%,3%9.8 Hz, H-3%), 1.82 (s,

3 H, CH₃, acetate), 1.56–1.49 (2 H, OCH₂CH₂), 1.32–

1.12 (10 H, CH₂, octyl), 0.87 (t, 3 H, J 7.0 Hz, CH₃,

octyl); ¹³C NMR (CDCl₃): l 169.4 (CO, acetate), 139.0,

138.8, 138.2, 138.0, 137.9 (aromatic quat.), 128.5, 128.4,

128.3, 128.2, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4,

127.3 (aromatic CH), 103.3 (C-1%), 100.0 (C-1), 81.9

(C-3%), 78.8 (C-3), 77.4 (C-4), 74.6, 73.8, 73.4, 72.3

(PhCH₂), 74.5 (C-5), 73.5 (C-4%), 72.9 (C-5%), 72.1 (C-

2%), 69.6 (OCH₂CH₂), 68.9 (C-6), 68.2 (C-6%), 55.0 (C-2)

31.9, 29.5, 26.3, 26.0, 24.7, 21.6 (CH₂, octyl), 20.8 (CH₃,

acetate), 14.1 (CH₃, octyl). Anal. Calcd for C₅₇H₇₁NO₁₁

(945.17): C, 72.36; H, 7.56. Found: C, 72.36; H, 7.71.

Octyl 3,4,6-tri-O-benzyl-i-

4)-3-O-benzyl-2-deoxy-6-O-p-methoxybenzyl-2-ph-

thalimido-i- -glucopyranoside (58).—Compound 57

D-galactopyranosyl-(1

D

(30 mg, 0.026 mmol) was dissolved in dry MeOH (1

mL), and sodium (0.5 mg) added. The solution was

stirred at rt for 48 h, neutralized with Amberlite IR-120

(H⁺) resin, ﬁltered and concentrated. Column chro-

matography (5:1 hexane–EtOAc) resulted in 58 (22 mg,

1

77%) as a colorless oil: H NMR (CDCl₃): l 7.80–7.60

(4 H, Phth), 7.38–6.80 (24 H, Ph), 5.04 (d, 1 H, J_1,28.6

Hz, H-1), 4.86, 4.84, 4.69, 4.66, 4.52, 4.51, 4.42, 4.31,

4.24 (d, 1 H, J 11.6 Hz, PhCH₂), 4.54 (d, 1 H, J_1%,2%7.7

Hz, H-1%), 4.36 (dd, 1 H, J_3,47.5, J_2,310.7 Hz, H-3),

4.14 (dd, 1 H, H-2), 4.07 (dd, 1 H, J_4,59.6 Hz, H-4)

3.99 (dd, 1 H, J_5,6a3.5, J_6a,6b11.4 Hz, H-6a), 3.90 (dd,

1 H, J_2%,3%9.8 Hz, H-2%), 3.85 (d, 1 H, J_3%,4%2.9 Hz, H-4%),

3.78–3.72 (5 H, H-6a%, H-6b, OCH₃), 3.61 (ddd, 1 H,

J_5,6b5.5 Hz, H-5), 3.48 (dt, 1 H, J 6.4, 9.2 Hz,

OCH₂CH₂), 3.41–3.32 (3 H, H-5%, H-6a%, OCH₂CH₂),

3.31 (dd, 1 H, J_3%,4%2.9, J_2%,3%9.9 Hz, H-3%), 3.22 (bs, 1 H,

OH), 1.40–1.32 (2 H, OCH₂CH₂), 1.08–0.95 (10 H,

CH₂, octyl), 0.88 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 159.3 (CO, Phth), 138.9, 138.8, 138.3,

137.9, 131.7 (aromatic quat), 133.6, 130.0, 129.7, 129.5,

127.8, 127.7, 127.6, 127.3, 127.2, 126.7, 123.2, 113.7

(aromatic CH), 103.6 (C-1%), 98.5 (C-1), 82.0 (C-3%),

78.6 (C-4), 78.5 (C-3, C-2%), 74.8 (C-5), 74.6, 74.4, 73.4,

73.2, 72.4 (PhCH₂), 73.5 (C-5%), 73.1 (C-4%), 72.4 (C-2%),

69.6 (OCH₂CH₂), 68.4, 68.1 (C-6, C-6%), 56.0 (C-2), 55.2

(OCH₃), 31.6, 29.3, 29.1, 29.0, 25.8, 22.5 (CH₂, octyl),

14.1 (CH₃, octyl). Anal. Calcd for C₆₄H₇₃NO₁₃

(1064.26): C, 72.23; H, 6.91. Found: C, 71.62; H, 6.82.

Octyl 2-O-acetyl-3,4,6-tri-O-benzyl-i-

ranosyl-(14)-3-O-benzyl-2-deoxy-6-O-p-methoxy-

benzyl-2-phthalimido-i- -glucopyranoside (57).—The

D-galactopy-

D

acceptor compound 34 (636 mg, 1.0 mmol) and the

donor compound 54 (1.00 g, 2.0 mmol) were dissolved

in dry DCM (20 mL) containing crushed 4 A molecular

,

sieves. The mixture was cooled to 0 °C, followed by the

addition of N-iodosuccinimide (450 mg 2.0 mmol) and

stirring for 45 min. A catalytic amount of silver triﬂate

was added, the mixture was stirred for an additional 2

h, ﬁltered through Celite, washed successively with

sodium bicarbonate, sodium thiosulfate, and water,

dried over magnesium sulfate and concentrated under

reduced pressure. Column chromatography (10:1 tolu-

ene–EtOAc) resulted in 57 (977 mg 88% based on the

1

acceptor) as a colorless oil: H NMR (CDCl₃): l 7.80–

Octyl 2,3,4,6-tetra-O-benzyl-i-

(14)-3-O-benzyl-2-deoxy-6-p-methoxybenzyl-2-ph-

thalimido-i- -glucopyranoside (59).—Compound 58

D-galactopyranosyl-

7.60 (4 H, Phth), 7.38–6.78 (24 H, Ph), 5.35 (dd, 1 H,

J_1%,2%7.9, J_2%3%10.0 Hz, H-2%), 5.07 (d, 1 H, J_1,28.5 Hz,

H-1), 4.91, 4.84, 4.68, 4.67, 4.49, 4.47, 4.46, 4.43, 4.40,

4.25 (d, 1 H, J 11.6 Hz, PhCH₂), 4.42 (d, 1 H, H-1%),

4.23 (dd, 1 H, J_3,48.4, J_2,310.8 Hz, H-3), 4.14 (dd, 1 H,

H-2), 3.97 (dd, 1 H, J_4,59.9 Hz, H-4), 3.91 (d, 1 H, J_3%,4%

2.9 Hz, H-4%), 3.79–3.73 (6 H, H-6a, H-6b, OCH₂CH_2,

CH₃), 3.52 (ddd, 1 H, J_5,6a=J_5,6b2.3 Hz, H-5), 3.46

(dd, 1 H, J_6a%,5%=J_6a%,6b%10.1 Hz, H-6a%), 3.42–3.32 (4 H,

H-3%, H-5%, H-6b%, OCH₂CH₂), 2.00 (s, 3 H, CH₃,

acetate), 1.42–1.30 (2 H, OCH₂CH₂), 1.20–0.85 (10 H,

D

(245 mg, 0.023 mmol) was dissolved in DMF (3 mL),

and tetrabutyl ammonium iodide (170 mg, 0.046 mmol)

was added. The solution was cooled to 0 °C, followed

by the addition of NaH (13 mg, 60% dispersion in oil,

0.033 mmol). The mixture was stirred for 15 min and

benzyl bromide (13 mL, 0.12 mmol) was added. Stirring

at 0 °C was continued for 30 min and the reaction was

quenched with MeOH, diluted with toluene, washed

successively with brine and water, dried over sodium

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2145

sulfate and concentrated under reduced pressure.

Octyl 2,3,4,6-tetra-O-benzyl-i-

D-galactopyranosyl-

Column chromatography (5:1 hexane–EtOAc) gave 59

(94 mg, 35%): H NMR (CDCl₃): l 7.85–7.60 (4 H,

(14)-2-acetamido-3-O-benzyl-2-deoxy-i-D-glucopy-

1

ranoside (61).—Compound 60 (98 mg, 0.095 mmol)

was dissolved in tert-butanol (5 mL) and ethylenedi-

amine (2 mL), heated to 90 °C, and stirred for 30 h.

The solution was cooled to rt and co-concentrated with

toluene. The resulting oil was dissolved in MeOH (5

mL) and Ac₂O (2 mL), and triethylamine (0.1 mL) was

added. The solution was stirred at rt for 2 h, followed

by the addition of EtOH (10 mL) and water (2 mL).

The solution was stirred for 15 min, washed succes-

sively with sodium bicarbonate and water, dried over

magnesium sulfate and concentrated under reduced

pressure. Column chromatography (6:1 toluene–

Phth), 7.40–6.80 (29 H, Ph), 5.08 (d, 1 H, J_1,28.4 Hz,

H-1), 4.92, 4.87, 4.81, 4.70, 4.51, 4.45, 4.35, 4.32, 4.22

(d, 1 H, J 11.6 Hz, PhCH₂), 4.41 (d, 1 H, J_1%,2%7.7 Hz,

H-1%), 4.26 (dd, 1 H, J_3,48.5, J_2,310.0 Hz, H-3), 4.16

(dd, 1 H, H-2), 4.02 (dd, 1 H, J_4,58.4 Hz, H-4) 3.88 (d,

1 H, J_3%,4%2.9 Hz, H-4%), 3.83 (dd, 1 H, J_5,6a4.1, J_6a,6b

10.8 Hz, H-6a), 3.79–3.72 (5 H, H-2%, OCH₂CH₂,

OCH₃), 3.68 (dd, 1 H, J_5,6b1.7 Hz, H-6b), 3.54 (ddd, 1

H, H-5), 3.47–3.37 (4 H, H-3%, H-5%, H-6a%, H-6b%), 3.34

(dt, 1 H, J 6.2, 9.0 Hz, OCH₂CH₂), 1.44–1.30 (2 H,

OCH₂CH₂), 1.10–0.90 (10 H, CH₂, octyl), 0.88 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 159.7 (CO,

Phth), 139.8, 139.7, 139.5, 139.3, 138.8, 130.0 (aromatic

quat.), 131.2, 129.1, 129.0, 128.9, 128.8, 128.6, 128.5,

128.4, 128.3, 128.2, 128.1, 127.9, 127.4, 113.7 (aromatic

CH), 103.7 (C-1%), 99.0 (C-1), 83.1 (C-3%), 80.8 (C-2%),

78.7 (C-4), 77.9 (C-3), 76.0, 75.2, 75.0, 74.5, 74.1, 73.7,

73.5, 73.4 (C-4%, C-5, C-5%, PhCH₂×5), 70.2

(OCH₂CH₂), 69.0 (C-6%), 68.5 (C-6), 56.5 (C-2), 55.9

(OCH₃), 32.3, 30.0, 29.9, 29.8, 26.5, 23.3 (CH₂, octyl),

14.7 (CH₃, octyl). HRESIMS Calcd for C₇₁H₇₉NO₁₃Na

1176.5449. Found 1176.5445.

1

EtOAc) gave 61 (70 mg, 82%) as a colorless oil: H

NMR (CDCl₃): l 7.35–7.18 (25 H, Ph), 5.59 (d, 1 H, J

7.6 Hz, NHAc), 4.95, 4.94, 4.81, 4.79, 4.70, 4.54, 4.52,

4.35, 4.25 (d, 1 H, J 11.6 Hz, PhCH₂), 4.91 (d, 1 H, J_1,2

7.7 Hz, H-1), 4.47 (d, 1 H, J_1%,2%7.7 Hz, H-1%), 4.10 (dd,

1 H, J_2,3=J_3,49.0 Hz, H-3), 3.92 (d, 1 H, J_3%,4%2.5 Hz,

H-4%), 3.86–3.74 (5 H, H-2%, H-4, H-6a%, H-6b%,

OCH₂CH₂), 3.54–3.48 (3 H, H-3%, H-6a, H-5), 3.46–

3.38 (3 H, H-5%, H-6b, OCH₂CH₂), 3.25 (ddd, 1 H, H-2)

1.84 (s, 3 H, CH₃NHAc), 1.56–1.48 (2 H, OCH₂CH₂),

1.32–1.18 (10 H, CH₂, octyl), 0.85 (t, 3 H, J 7.0 Hz,

CH₃, octyl); ¹³C NMR (CDCl₃): l 170.9 (CO, acetate),

139.7, 139.6, 139.2, 139.1, 138.3 (aromatic quat.), 129.1,

129.0, 128.9, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1

(aromatic CH), 104.0 (C-1%), 100.5 (C-1), 83.1 (C-3%),

80.7 (C-4), 78.4 (C-3), 76.4 (C-2%), 76.1, 75.4, 75.0, 74.5,

74.2, 73.9, 73.5 (C-4%, C-5, C-5%, PhCH₂×5), 70.7

(OCH₂CH₂), 68.9 (C-6), 62.1 (C-6%), 57.8 (C-2) 32.5,

30.3, 30.0, 29.9, 26.7, 24.5 (CH₂, octyl), 23.4 (CH₃,

acetate), 14.8 (CH₃, octyl). HRESIMS Calcd for

C₅₇H₇₁NO₁₁Na 968.4925. Found 968.4925.

Octyl 2,3,4,6-tetra-O-benzyl-i-

D-galactopyranosyl-

(14)-3-O-benzyl-2-deoxy-2-phthalimido-i-

D

-gluco-

pyranoside (60).—Compound 59 (95 mg, 0.082 mmol)

was dissolved in DCM (10 mL), and DDQ (29 mg, 0.13

mmol) was added. The solution was stirred at rt for 2 h,

and the reaction was quenched with 1,4-cyclohexadiene,

followed by successive washes of sodium bicarbonate

and water. The solution was dried over sodium sulfate

and concentrated under reduced pressure. Column

chromatography (8:1 toluene–acetone) resulted in 60

1

(49 mg, 59%): H NMR (CDCl₃): l 7.88–7.64 (4 H,

Octyl 2-O-acetyl-3,4,6-tri-O-benzyl-i-

ranosyl-(14)-3-O-allyl-6-O-benzyl-2-deoxy-2-ph-

thalimido-i- -glucopyranoside (62).—Compound 62

D-galactopy-

Phth), 7.38–6.80 (25 H, Ph), 5.13 (d, 1 H, J_1,28.5 Hz,

H-1), 4.93, 4.88, 4.85, 4.82, 4.70, 4.52, 4.46, 4.34, 4,24

(d, 1 H, J 11.6 Hz, PhCH₂), 4.51 (d, 1 H, J_1%,2%7.6 Hz,

H-1%), 4.27 (dd, 1 H, J_3,48.5, J_2,310.8 Hz, H-3), 4.11

(dd, 1 H, H-2), 3.91 (dd, 1 H, J_4,59.6 Hz, H-4),

3.90–3.83 (3 H, H-4%, H-6a%, H-6b%), 3.81 (dd, 1 H, J_2%,3%

9.7 Hz, H-2%), 3.73 (dt, 1 H, J 6.1, 9.8 Hz, OCH₂CH₂),

3.56–6.52 (2 H, H-3%, H-5), 3.48–3.38 (3 H, H-5%, H-6a,

H-6b), 3.34 (dt, 1 H, J 6.4, 9.8 Hz, OCH₂CH₂), 1.40–

1.28 (2 H, OCH₂CH₂), 1.18–0.88 (10 H, CH₂, octyl),

0.79 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃):

l 139.1, 139.0, 138.6, 138.5, 138.1, 133.7 (aromatic

quat), 131.7, 128.5, 128.4, 128.3, 128.2, 128.0, 127.8,

127.7, 127.6, 127.3, 126.8, 123.2 (aromatic CH), 103.4

(C-1%), 98.4 (C-1), 82.5 (C-3%), 80.1 (C-2%), 78.2 (C-4)

77.3 (C-3), 75.6, 74.5, 74.4, 73.8, 73.3 (PhCH₂), 75.5

(C-5%), 73.9 (C-4%), 72.8 (C-5), 69.9 (OCH₂CH₂), 68.7,

68.4 (C-6, C-6%), 56.3 (C-2) 31.6, 29.3, 29.2, 29.1, 25.8,

22.6 (CH₂, octyl), 14.1 (CH₃, octyl). HRESIMS Calcd

for C₆₃H₇₁NO₁₂Na 1056.4874. Found 1056.4877.

D

(1.85 g, 80% based on the acceptor) was synthesized

from acceptor 30 (2.14 g, 2.3 mmol), donor 54 (2.33 g,

4.3 mmol), N-iodosuccinimide (990 mg, 4.0 mmol), a

catalytic amount of silver triﬂate and dry DCM (40

,

mL) containing crushed 4 A molecular sieves as de-

scribed for the preparation of 57: H NMR (CDCl₃): l

1

7.80–7.70 (4 H, Phth), 7.38–7.18 (20 H, Ph), 5.44 (1 H,

OCH₂CHꢀCH₂), 5.26 (dd, 1 H, J_1%,2%7.9, J_2%,3%10.2 Hz,

H-2%), 5.08 (d, 1 H, J_1,28.1 Hz, H-1), 4.91–4.86 (2 H,

PhCH₂, OCH₂CHꢀCHH), 4.72 (d, 1 H, J 12.2 Hz,

PhCH₂), 4.68 (2 H, PhCH₂, OCH₂CHꢀCHH), 4.55–

4.37 (6 H, H-1%, PhCH₂×5), 4.31 (1 H, OCH-

HCHꢀCH₂), 4.14 (2 H, H-2, H-3), 3.91 (d, 1 H, J_3%,4%2.3

Hz, H-4%), 3.87 (dd, 1 H, J_3,48.1, J_4,59.9 Hz, H-4),

3.83–3.72 (4 H, H-6a, H-6b, OCH₂CH₂, OCH-

HCHꢀCH₂), 3.61 (dd, 1 H, J_5%,6a%=J_6a%,6b%9.0 Hz, H-

6a%), 3.55 (dd, 1 H, J_5%,6b%5.2 Hz, H-6b%), 3.51 (ddd, 1 H,

J 2.9, 5.0, 9.9 Hz, H-5), 3.42 (dd, 1 H, H-5%), 3.36 (dt,

2146

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

1 H, J 6.4, 9.0 Hz, OCH₂CH₂), 3.33 (dd, 1 H, J_2%,3%10.0

Hz, H-3%), 1.96 (s, 3 H, CH₃, acetate), 1.42–1.32 (2 H,

OCH₂CH₂), 1.18–0.90 (10 H, CH₂, octyl), 0.88 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 169.3 (CO,

acetate), 138.8, 138.2, 138.1, 138.0 (aromatic quat.),

135.1 (CH₂ꢀCHCH₂O), 133.9, 131.8, 128.5, 128.4,

128.3, 128.1, 127.9, 127.8, 127.7, 127.6, 127.4, 127.3

(aromatic CH), 116.2 (CH₂ꢀCHCH₂O), 100.8 (C-1%),

98.4 (C-1), 80.4, 77.8, 77.6, 75.1, 74.3 (C-2%, C-3, C-3%,

C-4, C-4%), 73.7, 73.6, 73.5, 72.6, 71.7 (C-5, C-5%,

PhCH₂, CH₂ꢀCHCH₂O), 69.6 (OCH₂CH₂), 68.2, 68.1

(C-6, C-6%), 56.0 (C-2) 31.6, 29.3, 29.2, 29.1, 25.9, 22.6

(CH₂, octyl), 21.1 (CH₃, acetate), 14.1 (CH₃, octyl).

Anal. Calcd for C₆₁H₇₁NO₁₃(1026.22): C, 71.39; H,

6.97. Found: C, 71.13; H, 7.00.

4.52, 4.44 (d, 1 H, J 11.2 Hz, PhCH₂), 4.70–4.65 (4 H,

H-1%, PhCH₂×2, OCH₂CHꢀCHH), 4.40–4.32

(PhCH₂×2, OCHHCHꢀCH₂), 4.20–4.12 (2 H, H-2,

H-3), 3.93 (dd, 1 H, J_3,48.2, J_4,59.9 Hz, H-4), 3.88–

3.84 (2 H, H-4%, OCHHCHꢀCH₂), 3.81 (dd, 1 H, J_5,6a

4.4, J_6a,6b10.8 Hz, H-6a), 3.77 (dt, 1 H, J 6.7, 9.9 Hz,

OCH₂CH₂), 3.71 (dd, 1 H, J_5,6b1.7 Hz, H-6b), 3.68 (dd,

1 H, J_1%,2%7.7, J_2%,3%9.7 Hz, H-2%), 3.59 (dd, 1 H,

J_6a%,5%=J_6a%,6b%8.2 Hz, H-6a%), 3.56–3.50 (2 H, H-5%,

H-6b%), 3.40–3.32 (3 H, H-3%, H-5, OCH₂CH₂), 1.42–

1.34 (2 H, OCH₂CH₂), 1.18–0.90 (10 H, CH₂, octyl),

0.78 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃):

l 139.8, 139.5, 139.3, 139.2, 138.8 (aromatic quat.),

136.1 (CH₂ꢀCHCH₂O), 134.6, 132.5, 129.1, 129.0,

128.9, 128.8, 128.6, 128.5, 128.4, 128.2, 128.1, 127.9

(aromatic CH), 116.7 (CH₂ꢀCHCH₂O), 103.6 (C-1%),

99.1 (C-1), 83.1 (C-3%), 80.7 (C-2%), 78.4 (C-4), 78.2 (C-2,

C-3), 76.1, 76.0, 75.1, 74.4, 74.3, 73.8, 73.3 (C-4%, C-5,

C-5%, PhCH₂×5, CH₂ꢀCHCH₂O), 70.2 (OCH₂CH₂),

69.1, 69.0 (C-6, C-6%), 56.8 (C-2) 32.4, 30.0, 29.9, 29.8,

26.5, 23.3 (CH₂, octyl), 14.7 (CH₃, octyl). Anal. Calcd

for C₆₆H₇₅NO₁₂(1074.30): C, 73.79; H, 7.04. Found: C,

73.79; H, 7.20.

Octyl 3,4,6-tri-O-benzyl-i-

D-galactopyranosyl-(1

4)-3-O-allyl-6-O-benzyl-2-deoxy-2-phthalimido-i-

D-

glucopyranoside (63).—Compound 63 (1.31 g 78% mg,

77%) was synthesized from 62 (1.76 g, 1.74 mmol),

MeOH (50 mL), and sodium (12 mg) as described for

1

the preparation of 58: H NMR (CDCl₃): l 7.88–7.70

(4 H, Phth), 7.38–7.20 (20 H, Ph), 5.44 (1 H,

OCH₂CHꢀCH₂), 5.07 (d, 1 H, J_1,28.6 Hz, H-1), 4.90–

4.84 (2 H, PhCH₂, OCH₂CHꢀCHH), 4.72–4.52 (7 H,

H-1%, PhCH₂×5, OCH₂CHꢀCHH), 4.39, 4.35 (d, 1 H,

J 11.9 Hz, PhCH₂), 4.28 (1 H, OCHHCHꢀCH₂), 4.24

(dd, 1 H, J_3,48.5, J_2,310.7 Hz, H-3), 4.13 (dd, 1 H,

H-2), 4.02–3.97 (2 H, H-4, H-6a), 3.87–3.74 (4 H, H-2%,

H-6b, OCH₂CH₂, OCHHCHꢀCH₂), 3.62–3.56 (2 H,

H-5, H-6a%), 3.52–3.44 (2 H, H-5%, H-6b%), 3.35 (dt, 1 H,

J 6.4, 9.2 Hz, OCH₂CH₂), 3.31 (dd, 1 H, J_3%,4%2.9, J_2%,3%

9.7 Hz, H-3%), 3.27 (d, 1 H, H-4%), 1.44–1.30 (2 H,

OCH₂CH₂), 1.18–0.90 (10 H, CH₂, octyl), 0.78 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 139.5,

139.0, 138.6, 138.5 (aromatic quat.), 135.6

(CH₂ꢀCHCH₂O), 134.7, 132.5, 129.1, 129.0, 128.8,

128.7, 128.5, 128.4, 128.3, 128.0 (aromatic CH), 116.7

(CH₂ꢀCHCH₂O), 104.5 (C-1%), 99.2 (C-1), 82.5 (C-3%,

C-4%), 79.3 (C-3), 78.9 (C-4), 75.4 (C-5), 75.0, 74.2, 74.1,

73.7, 73.1 (C-5%, PhCH₂×4, CH₂ꢀCHCH₂O), 70.3

(OCH₂CH₂), 69.2, 69.1 (C-6, C-6%), 56.8 (C-2) 32.4,

30.0, 29.9, 29.8, 26.5, 23.3 (CH₂, octyl), 14.7 (CH₃,

octyl). Anal. Calcd for C₅₉H₆₉NO₁₂(983.48): C, 72.00;

H, 7.07. Found: C, 71.69; H, 7.14.

Octyl

2,3,4,6-tetra-O-benzyl-i-

D-galactopyanosyl-

(14)-6-O-benzyl-2-deoxy-2-phthalimido-i-

D

-gluco-

pyranoside (65).—Compound 64 (1.03 g, 0.91 mmol)

was dissolved in dry MeOH (50 mL), and palladium

chloride (25 mg, 0.14 mmol) was added. The solution

was stirred at rt for 3 h. The solvent was concentrated,

and the crude product was puriﬁed without further

workup. Column chromatography (10:1 toluene–

EtOAc) resulted in 65 (781 mg, 95%) as a colorless oil:

¹H NMR (CDCl₃): l 7.88–7.70 (4 H, Phth), 7.38–7.20

(25 H, Ph), 5.16 (d, 1 H, J_1,28.5 Hz, H-1), 4.88, 4.84,

4.76, 4.69, 4.51(d, 1 H, J 11.6 Hz, PhCH₂), 4.43 (dd, 1

H, J_3,48.2, J_2,310.8 Hz, H-3), 4.39–4.25 (6 H, H-1%,

PhCH₂×5), 4.16 (dd, 1 H, H-2), 3.82–3.74 (4 H, H-2%,

H-4%, H-6a, OCH₂CH₂), 3.71–3.64 (2 H, H-5, H-6),

3.59 (dd, 1 H, J_4,58.3 Hz, H-4), 3.55–3.51 (2 H, H-5%,

H-6a%), 3.48–3.42 (2 H, H-3%, H-6b%), 3.39 (dt, 1 H, J

6.4, 9.8 Hz, OCH₂CH₂), 1.45–1.18 (2 H, OCH₂CH₂),

1.15–0.82 (10 H, CH₂, octyl), 0.80 (t, 3 H, J 7.0 Hz,

CH₃, octyl); ¹³C NMR (CDCl₃): l 138.6, 138.5, 138.4,

138.2, 137.5, 133.8 (aromatic quat.), 132.0, 128.5, 128.4,

128.3, 128.1, 128.0, 127.9, 127.8, 127.6, 127.4 (aromatic

CH), 82.4 (C-1%), 82.2 (C-1), 79.0 (C-3%, C-4), 77.4

(C-2%), 75.5, 74.8, 74.7, 73.6, 73.3, 73.1, 73.0 (C-4%, C-5,

C-5%, PhCH₂×5), 69.8 (C-3), 69.7 (OCH₂CH₂), 68.7,

68.4 (C-6, C-6%), 56.3 (C-2) 31.7, 29.3, 29.2, 25.9, 22.6

(CH₂, octyl), 14.1 (CH₃, octyl).

Octyl 2,3,4,6-tetra-O-benzyl-i-

(14)-3-O-allyl-6-O-benzyl-2-deoxy-2-phthalimido-i-

-glucopyranoside (64).—Compound 64 (94 mg, 35%,

D-galactopyranosyl-

D

30% unreacted starting material 63) was synthesized

from compound 63 (115 mg, 0.12 mmol), DMF (2 mL),

tetrabutylammonium iodide (90 mg, 0.24 mmol), benzyl

bromide (26 mL, 0.24 mmol) and NaH (10 mg, 60%

dispersion in oil, 0.25 mmol) as described for the prepa-

ration of 59: ¹H NMR (CDCl₃): l 7.88–7.70 (4 H,

Phth), 7.40–7.18 (25 H, Ph), 5.47 (1 H,

OCH₂CHꢀCH₂), 5.10 (d, 1 H, J_1,28.1 Hz, H-1), 4.89 (1

H, J_cis10.5 Hz, OCH₂CHꢀCHH), 4.91, 4.78, 4.76, 4.53,

Octyl 2,3,4,6-tetra-O-benzyl-i-

D-galactopyranosyl-

(14)-6-O-benzyl-2-deoxy-2-acetamido-i-

D

-glucopy-

ranoside (66).—Compound 66 (615 mg, 96%) was syn-

thesized from compound 65 (700 mg, 0.68 mmol),

tert-butanol (35 mL) and ethylenediamine (10 mL),

followed by Ac₂O (15 mL), MeOH (35 mL) and triethy-

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2147

lamine (0.5 mL) as described for the preparation of 61:

¹H NMR (CDCl₃): l 7.38–7.20 (25 H, Ph), 5.53 (d, 1

H, J 7.5 Hz, NHAc), 4.90, 4.82, 4.73, 4.70, 4.54, 4.42,

4.35, 4.28 (d, 1 H, J 11.5 Hz, PhCH₂), 4.85 (d, 1 H, J_1,2

8.2 Hz, H-1), 4.29 (d, 1 H, J_1%,2%7.9 Hz, H-1%), 4.27 (dd,

1 H, J_2,3=J_3,49.0 Hz, H-3), 3.85 (d, 1 H, J_3%,4%2.5 Hz,

H-4%), 3.83 (dt, 1 H, J 6.4, 9.0 Hz, OCH₂CH₂), 3.76 (dd,

1 H, J_2%,3%9.7 Hz, H-2%), 3.69 (d, 1 H, J_5,6a1.5, J_6a,6b10.7

Hz, H-6a), 3.61 (d, 1 H, J_5,6b5.0 Hz, H-6b), 3.58–3.45

(6 H, H-4, H-5, H-5%, H-6a%, H-6b%, OCH₂CH₂), 3.44

(dd, 1 H, H-3%), 3.25 (ddd, 1 H, H-2) 1.98 (s, 3 H, CH₃

NHAc), 1.60–1.50 (2 H, OCH₂CH₂), 1.35–1.20 (10 H,

CH₂, octyl), 0.85 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 170.9 (CO, acetate), 139.2, 139.1,

138.9, 138.3 (aromatic quant), 129.2, 129.1, 129.0,

128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2,

128.0 (aromatic CH), 104.4 (C-1%), 100.5 (C-1), 83.0

(C-3%), 82.4 (C-4), 79.7 (C-2%), 76.1, 75.3, 75.1, 74.3,

74.2, 74.0, 73.9, 73.6 (C-4%, C-5, C-5%, PhCH₂×5), 72.0

(C-3), 70.4 (OCH₂CH₂), 69.4, 68.9 (C-6, C-6%), 58.5

(C-2) 32.5, 30.3, 30.0, 26.7, 24.5 (CH₂, octyl), 23.4

(CH₃, acetate), 14.8 (CH₃, octyl). Anal. Calcd for

C₅₇H₇₁NO₁₁(945.17): C, 72.36; H, 7.56. Found: C,

75.59; H, 7.65.

(C-2) 31.8, 29.6, 29.4, 29.3, 26.0, 23.6 (CH₂, octyl), 22.7

(CH₃, acetate), 14.1 (CH₃, octyl). HRESIMS Calcd for

C₆₉H₈₀NO₁₄NaP 1200.5214. Found 1200.5230.

Octyl 6-O-phosphono-i-

D-galactopyanosyl-(14)-2-

acetamido-2-deoxy-i- -glucopyranoside, disodium salt

D

(5).—Compound 67 (25 mg, 0.021 mmol) was dissolved

in 95% EtOH (2 mL) containing 5% palladium-on-acti-

vated-charcoal (12 mg), and the mixture was stirred

under hydrogen at ambient pressure for 15 h. The

catalyst was removed by ﬁltration, the solvent was

evaporated, and the residue was redissolved in 95%

EtOH (2 mL). Adams’ catalyst (PtO₂) was added, and

the mixture was again stirred under hydrogen at ambi-

ent pressure for 15 h. The catalyst was removed by

ﬁltration, and the solvent was concentrated. The result-

ing residue was redissolved in water and puriﬁed using

a C₁₈Sep-Pak cartridge. The carbohydrate-containing

fractions were pooled, concentrated and converted to

the sodium salt by passage through Dowex 50-X8

(Na⁺) cation-exchange resin. Lyophilization of the elu-

1

ent provided 5 (8 mg, 65%): H NMR (D₂O (0.05 M

NaDCO₃/0.045 M NaOD)): l 4.50 (d, 1 H, J_1,27.7 Hz,

H-1), 4.47 (d, 1 H, J_1%,2%7.9 Hz, H-1%), 4.03 (d, 1 H, J_3%,4%

3.6 Hz, H-4%), 3.97 (dd, 1 H, J_5,6a2.3, J_6a,6b12.2 Hz,

H-6a), 3.88 (1 H, H-6a%), 3.87 (1 H, OCH₂CH₂), 3.86 (1

H, H-6b%), 3.81 (2 H, H-5, H-6b), 3.70 (1 H, H-3), 3.69

(1 H, H-4), 3.68 (1 H, H-2), 3.67 (1 H, H-3%), 3.57 (1 H,

OCH₂CH₂), 3.56 (1 H, H-5%), 3.52 (dd, 1 H, J_2%,3%10.0

Hz, H-2%), 2.05 (s, 3 H, CH₃, acetate), 1.56–1.50 (2 H,

OCH₂CH₂), 1.62–1.46 (10 H, CH₂, octyl), 0.85 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (D₂O (0.05 M

NaDCO₃/0.045 M NaOD)): l 102.6 (C-1%), 101.9 (C-1),

76.2 (C-5), 76.0 (C-5%), 74.8 (C-4), 73.8 (C-3%), 73.3

(C-3), 71.2 (OCH₂CH₂), 70.9 (C-2%), 69.4 (C-4%), 61.6,

61.7 (C-6, C-6%), 56.8 (C-2), 32.1, 29.4, 29.3, 29.1, 25.5,

22.3 (CH₂, octyl), 29.2 (CH₃, acetate). HRESIMS

Calcd for C₂₂H₄₁NO₁₄Na₂P 620.2060. Found 620.2057.

Octyl 2,4,6-tri-O-benzyl-3-O-diphenoxyphosphono-i-

Octyl 2,3,4-tri-O-benzyl-6-O-diphenoxyphosphono-i-

D

-galactopyranosyl-(14)-2-acetamido-3,6-di-O-ben-

zyl-2-deoxy-i- -glucopyranoside (67).—Compound 47

D

(30 mg, 0.32 mmol) was dissolved in pyridine (1 mL),

and the solution was cooled to 0 °C. To the cooled

solution, a catalytic amount of 4-dimethylaminopy-

ridine, and diphenyl phosphorochloridate (30 mL, 0.14

mmol) were added, and the mixture was allowed to

warm to rt. The solution was stirred for 24 h, diluted

with DCM, washed sequentially with water, sodium

bicarbonate, and water and concentrated under reduced

pressure. Column chromatography (5:1 toluene–ace-

tone) gave unreacted starting material (5 mg, 16%) and

67 (27 mg, 72%): ¹H NMR (CDCl₃): l 7.38–7.10 (35 H,

Ph), 5.67 (d, 1 H, J 7.5 Hz, NHAc), 4.94, 4.85, 4.80,

4.77, 4.68, 4.55, 4.53, 4.46, 4.36 (d, 1 H, J 11.2 Hz,

PhCH₂), 4.89 (d, 1 H, J_1,27.3 Hz, H-1), 4.39 (d, 1 H,

J_1%,2%7.7 Hz, H-1%), 4.19–4.09 (3 H, H-3, H-6a%, H6b%),

(dd, 1 H, J_3,4=J_4,58.2 Hz, H-4), 3.83–3.78 (3 H, H-4%,

H-6a, OCH₂CH₂), 3.74–3.70 (2 H, H-2%, H-6b), 3.56

(ddd, 1 H, J_5,6a=J_5,6b4.0 Hz, H-5), 3.43 (dt, 1 H, J 6.8,

9.7 Hz, OCH₂CH₂), 3.38 (dd, 1 H, J_5%,6a%=J_5%,6b%7.1 Hz,

H-5%), 3.33–3.28 (2 H, H-2, H-3%), 1.84 (s, 3 H, CH₃,

acetate), 1.60–1.50 (2 H, OCH₂CH₂), 1.34–1.20 (10 H,

CH₂, octyl), 0.85 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 138.9, 138.6, 138.5, 138.4, 138.3

(aromatic quat.), 130.0, 128.4, 128.3, 128.2, 128.1,

128.0, 127.7, 127.6, 127.4, 125.5, 120.1 (aromatic CH),

102.9 (C-1%), 99.7 (C-1), 82.0 (C-3%), 79.6 (C-2%), 77.5

(C-3), 77.3 (C-4), 75.3, 74.7, 74.0, 73.1, 72.9 (PhCH₂),

75.1 (C-5), 73.0 (C-4%), 72.2 (d, J_5’,P8.4 Hz, C-5%), 69.7

(OCH₂CH₂), 68.5 (C-6), 66.0 (d, J_6’,P5.4 Hz, C-6%), 56.4

D

-galactopyranosyl-(14)-2-acetamido-3,6-di-O-ben-

zyl-2-deoxy-i- -glucopyranoside (68).—Compound 68

D

(22 mg, 80%) was synthesized from 53 (23 mg, 0.024

mmol), a catalytic amount of 4-dimethylamino pyri-

dine, diphenyl phosphorochloridate (30 mL, 0.14 mmol)

and pyridine (1 mL) as described for the preparation of

1

67: H NMR (CDCl₃): l 7.38–7.10 (35 H, Ph), 5.67 (d,

1 H, J 7.3 Hz, NHAc), 4.89 (d, 1 H, J_1,27.5 Hz, H-1),

4.88, 4.76, 4.68, 4.64, 4.53, 4.37, 4.34, 4.24 (d, 1 H, J

11.2 Hz, PhCH₂), 4.56 (ddd, 1 H, J_3%,4%3.3, J_2%,3%J_3%,P8.6,

H-3%), 4.43 (d, 1 H, J_1%,2%7.7 Hz, H-1%), 4.12 (dd, 1 H,

J_2,3=J_3,48.0 Hz, H-3), 4.06 (d, 1 H, H-4%), 3.93 (dd, 1

H, J_4,58.2 Hz, H-4), 3.81–3.72 (3 H, H-2%, H-6a,

OCH₂CH₂), 3.63 (dd, 1 H, J_5,6b2.8, J_6a,6b10.6 Hz,

H-6b), 3.49–3.36 (5 H, H-5, H-5%, H-6a%, H-6b%,

OCH₂CH₂), 3.24 (ddd, 1 H, H-2), 1.82 (s, 3 H, CH₃,

acetate), 1.56–1.50 (2 H, OCH₂CH₂), 1.30–1.20 (10 H,

CH₂, octyl), 0.88 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

2148

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

NMR (CDCl₃): l 171.8 (CO, acetate), 152.1, 140.4,

140.0, 139.7, 139.6, 139.4 (aromatic quat), 131.2, 129.8,

129.7, 129.4, 129.3, 129.1, 129.0, 128.8, 126.8, 121.1

(aromatic CH), 103.9 (C-1%), 100.8 (C-1), 82.4 (d, J_3’,P

6.7 Hz, C-3%), 79.2 (d, J_2’,P5.5 Hz, C-2%), 77.3 (C-3),

76.8 (C-4), 76.5 (C-4%), 76.2, 76.1, 75.3, 74.4, 74.2

(PhCH₂), 76.0 (C-5), 73.5 (C-5%), 70.7 (OCH₂CH₂), 69.4

(C-6), 68.7 (C-6%), 57.7 (C-2) 32.7, 30.4, 30.3, 30.2, 26.8,

23.5 (CH₂, octyl), 24.9 (CH₃, acetate), 14.9 (CH₃, oc-

tyl). HRESIMS Calcd for C₆₉H₈₀NO₁₄NaP 1200.5214.

Found 1200.5235.

100.2 (C-1), 81.4 (C-3%), 79.8 (C-4%, C-2%), 78.3 (C-3),

77.9 (C-4), 75.9 (C-5), 75.8, 74.8, 74.1, 73.8, 73.3, 72.9

(C-5%, PhCH₂×5), 70.4 (OCH₂CH₂), 69.4 (PhCH₂),

69.2 (C-6), 68.7 (C-6%), 64.6, 64.1 (PhCH₂), 57.2 (C-2)

32.3, 30.2, 30.1, 30.0, 26.7, 23.5 (CH₂, octyl), 24.3 (CH₃,

acetate), 14.8 (CH₃, octyl). HRESIMS Calcd for

C₇₁H₈₄NO₁₃NaP 1212.5578. Found 1212.5587.

Octyl 2,3,6-tri-O-benzyl-4-O-dibenzylphosphono-i-

galactopyranosyl-(14)-2-acetamido-3,6-di-O-benzyl-

2-deoxy-i- -glucopyranoside (73).—Compound 73 (8

D-

D

mg, 79%) was synthesized from compound 69 (10 mg,

8.4×10⁻³mmol), 30% hydrogen peroxide (0.5 mL)

and tetrahyrofuran (2 mL), as described for the prepa-

Octyl 3-O-phosphono-i-

D-galactopyranosyl-(14)-

2-acetamido-2-deoxy-i- -glucopyranoside disodium salt

D

1

(7).—Compound 7 (6 mg, 56%) was synthesized from

68 (20 mg, 0.017 mmol) as described for the prepara-

ration of 74: H NMR (CDCl₃): l 7.41–7.05 (35 H,

Ph), 5.63 (d, 1 H, J 7.6 Hz, NHAc), 5.07 (dd, 1 H, J_3%,4%

2.9 Hz, H-4%), 4.98–4.84 (7 H, H-1, PhCH₂×6), 4.66,

4.62, 4.35, 4.24 (d, 1 H, J 11.7 Hz, PhCH₂), 4.56–4.50

(3 H, PhCH₂), 4.40 (d, 1 H, J_1%,2%7.7 Hz, H-1%), 4.14 (dd,

1 H, J_2,3=J_3,48.2 Hz, H-3), 3.92 (dd, 1 H, J_4,58.4 Hz,

H-4), 3.82–3.78 (2 H, H-6a, OCH₂CH₂), 3.69 (dd, 1 H,

1

tion of 5: H NMR (D₂O (0.05 M NaDCO₃/0.045 M

NaOD)): l 4.54 (d, 1 H, J_1%,2%7.9 Hz, H-1%), 4.50 (d, 1

H, J_1,28.1 Hz, H-1), 4.03 (d, 1 H, J_3%,4%3.3 Hz, H-4%),

4.23 (ddd, 1 H, J_2%,3%=J_3%,P8.4 Hz, H-3%), 3.97 (dd, 1 H,

J_5,6a2.0, J_6a,6b12.1 Hz, H-6a), 3.87 (dt, 1 H, J 6.0, 10.5

Hz, OCH₂CH₂), 3.76 (2 H, H-6a%, H-6b%), 3.73 (1 H,

H-3), 3.74 (1 H, H-4), 3.71 (1 H, H-2), 3.69 (1 H, H-5%),

3.66 (dd, 1 H, H-2%), 3.67 (1 H, H-3), 3.57 (1 H,

OCH₂CH₂), 3.56 (1 H, H-5), 2.05 (s, 3 H, CH₃, ace-

tate), 1.56–1.50 (2 H, OCH₂CH₂), 1.32–1.26 (10 H,

CH₂, octyl), 0.85 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (D₂O (0.05 M NaDCO₃/0.045 M NaOD)): l

103.8 (C-1%), 102.1 (C-1), 79.3 (C-5%), 78.2 (C-4), 77.6

(C-3%), 76.5 (C-2%), 75.7 (C-5), 73.2 (C-3), 71.8 (C-2%),

71.2 (OCH₂CH₂), 69.1 (C-4%), 62.9 (C-6%), 60.8 (C-6),

56.5 (C-2), 31.7, 29.3, 29.1, 29.0, 25.6, 22.4 (CH₂, octyl),

23.3 (CH₃, acetate), 14.8 (CH₃, octyl). HRESIMS

Calcd for C₂₂H₄₁NO₁₄Na₂P 620.2060. Found 620.2067.

J_5,6b2.6, J_6a,6b10.7 Hz, H-6b), 3.59 (dd, 1 H, J_6a%,5%

=

J_6a%,6b%8.4 Hz, H-6a%), 3.53 (ddd, 1 H, J_5,6a4.7 Hz, H-5),

3.46–3.34 (5 H, H-2%, H-3%, H-5%, H-6b%, OCH₂CH₂),

3.21 (ddd, 1 H, H-2), 1.85 (s, 3 H, CH₃, acetate),

1.60–1.50 (2 H, OCH₂CH₂), 1.30–1.20 (10 H, CH₂,

octyl), 0.85 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C NMR

(CDCl₃): l 170.9 (CO, acetate), 139.5, 139.1, 139.0,

138.7, 138.6 (aromatic quat.), 137.0, 136.7 (d, J 7.9 Hz,

aromatic quat), 129.1, 129.0, 128.9, 128.7, 128.6, 128.5,

128.4, 128.3, 128.2, 128.0 (aromatic CH), 103.4 (C-1%),

100.2 (C-1), 80.6 (d, J_3’,P1.3 Hz, C-3%), 79.3 (C-2%), 78.3

(C-3), 77.8 (C-4), 76.0 (C-5), 75.3, 75.0, 74.1, 74.0, 73.0

(C-5%, PhCH₂×5), 73.5 (d, J_4’,P5.5 Hz, C-4%), 72.8 (d,

J_5’,P4.7 Hz, C-5%), 70.4 (OCH₂CH₂), 69.8, 69.7 (d, J 2.4

Hz, PhCH₂), 69.1 (C-6), 68.4 (C-6%), 57.6 (C-2) 32.3,

30.2, 30.1, 30.0, 26.7, 23.4 (CH₂, octyl), 24.3 (CH₃,

acetate), 14.8 (CH₃, octyl). HRESIMS Calcd for

C₇₁H₈₄NO₁₄NaP 1228.5527. Found 1228.5535.

Octyl 2,3,6-tri-O-benzyl-4-O-dibenzylphosphityl-i-

galactopyranosyl-(14)-2-acetamido-3,6-di-O-benzyl-

2-deoxy-i- -glucopyranoside (69).—Compound 69 (11

D-

D

mg, 58%) was synthesized from compound 49 (15 mg,

0.016 mmol), 1,2,4-triazole (8 mg), dibenzyl N,N-di-

ethylphosphoramidite, (10 mL, 0.031 mmol) and DCM

as described for the preparation of 70: ¹H NMR

(CDCl₃): l 7.38–7.10 (35 H, Ph), 5.64 (d, 1 H, J 7.3 Hz,

NHAc), 5.10–5.05, 4.94–4.84 (5 H, PhCH₂), 4.79–4.75

(4 H, H-1, PhCH₂×3), 4.68–4.52 (7 H, PhCH₂), 4.43

(d, 1 H, J_1%,2%7.9 Hz, H-1%), 4.36, 4.34, 4.28 (d, 1 H, J

11.2 Hz, PhCH₂), 4.10 (dd, 1 H, J_2,3=J_3,48.2 Hz, H-3),

3.92 (dd, 1 H, J_4,58.3 Hz, H-4), 3.82–3.77 (2 H, H-6a,

OCH₂CH₂), 3.71 (dd, 1 H, J_5,6b2.7, J_6a,6b10.6 Hz,

H-6b), 3.59–3.54 (3 H, H-4%, H-5, H-6a%), 3.48–3.40 (3

H, H-5%, H-6b%, OCH₂CH₂), 3.35 (dd, 1 H, J_3%,4%3.1, J_2%,3%

9.7 Hz, H-3%), 3.27 (ddd, 1 H, H-2), 1.83 (s, 3 H, CH₃,

acetate), 1.56–1.48 (2 H, OCH₂CH₂), 1.30–1.20 (10 H,

CH₂, octyl), 0.85 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 170.8 (CO, acetate), 139.7, 139.3,

139.2, 139.1, 139.0, 138.7, 138.6 (aromatic quat), 129.4,

129.3, 129.2, 129.1, 129.0, 128.9, 128.7, 128.6, 128.4,

128.3, 128.2, 128.1, 127.9 (aromatic CH), 103.7 (C-1%),

Octyl 4-O-phosphono-i-

D-galactopyanosyl-(14)-2-

acetamido-2-deoxy-i- -glucopyranoside disodium salt

D

(6).—Compound 6 (3 mg, 73%) was synthesized from

compound 73 (8 mg, 6.6×10⁻³mmol), 5% palladium-

on-charcoal (9 mg) and 95% EtOH (1 mL) as described

for the preparation of 8: ¹H NMR (D₂O (0.05 M

NaDCO₃/0.045 M NaOD)): l 4.50 (d, 1 H, J_1,27.1 Hz,

H-1), 4.47 (d, 1 H, J_1%,2%7.6 Hz, H-1%), 4.38 (dd, 1 H,

J_3%,4%1.1, J_4%,P9.0 Hz, H-4%), 3.96 (dd, 1 H, J_5,6a2.2, J_6a,6b

12.2 Hz, H-6a), 3.87 (dt, 1 H, J 5.9, 10.2 Hz,

OCH₂CH₂), 3.82 (dd, 1 H, J_5,6b5.1 Hz, H-6b), 3.79 (1

H, H-5%), 3.75 (2 H, H-6a%, H-6b%), 3.69 (1 H, H-2), 3.68

(1 H, H-3), 3.66 (1 H, H-4), 3.63 (2 H, H-2%, H-3%), 3.58

(1 H, OCH₂CH₂), 3.56 (1 H, H-5), 2.05 (s, 3 H, CH₃,

acetate), 1.62–1.50 (2 H, OCH₂CH₂), 1.32–1.20 (10 H,

CH₂, octyl), 0.85 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (D₂O (0.05 M NaDCO₃/0.045 M NaOD)): l

104.0 (C-1%), 101.6 (C-1), 79.7 (C-4), 75.6 (C-5%), 75.5

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2149

(C-5), 73.8 (C-3%), 73.1 (C-3), 72.4 (C-2%), 71.7 (C-4%),

71.4 (OCH₂CH₂), 61.4 (C-6%), 61.1 (C-6), 56.2 (C-2),

33.1, 29.2, 29.0, 28.9, 25.8, 22.4 (CH₂, octyl), 23.4 (CH₃,

acetate), 14.8 (CH₃, octyl). HRESIMS Calcd for

C₂₂H₄₁NO₁₄Na₂P 620.2060. Found 620.2061.

3.77 (dd, 1 H, J_5,6a4.2, J_6a,6b10.1 Hz, H-6a), 3.74 (dt,

1 H, J 6.6, 9.2 Hz, OCH₂CH₂), 3.66 (dd, 1 H, J_5,6b5.5

Hz, H-6b), 3.56–3.52 (2 H, H-5, H-6a%), 3.45–3.42 (2

H, H-3%, H-6b%), 3.38 (dd, 1 H, J 5.5, 7.9 Hz, H-5%), 3.31

(dt, 1 H, J 6.8, 9.5 Hz, OCH₂CH₂), 1.92 (s, 3 H, CH₃,

acetate), 1.54–1.46 (2 H, OCH₂CH₂), 1.30–1.20 (10 H,

CH₂, octyl), 0.87 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 170.9 (CO, acetate), 139.6, 139.2,

139.1, 138.5, 138.4 (aromatic quat.), 136.8, 136.7 (d, J

7.9 Hz, aromatic quat), 129.2, 129.1, 129.0, 128.9,

128.8, 128.6, 128.5, 128.4, 128.3, 128.2, 127.9 (aromatic

CH), 100.8 (C-1), 100.3 (d, J_1’,P3.7 Hz, C-1%), 81.6 (d,

J_3’,P3.6 Hz, C-3%), 78.5 (C-3), 78.1 (d, J_2’,P6.0 Hz, C-2%),

75.5, 74.2, 74.0, 73.4, 73.0 (PhCH₂), 75.4 (C-5), 74.4

(C-4), 73.9 (C-5%), 73.7 (C-4%), 70.2 (C-6), 70.1

(OCH₂CH₂), 70.0, 69.9 (d, J 5.4 Hz, PhCH₂), 68.6

(C-6%), 52.1 (C-2) 32.6, 30.3, 30.1, 30.0, 26.7, 23.4 (CH₂,

octyl), 24.0 (CH₃, acetate), 14.8 (CH₃, octyl). HRES-

IMS Calcd for C₇₁H₈₄NO₁₄NaP 1228.5527. Found

1228.5528.

Octyl 3,4,6-tri-O-benzyl-2-O-dibenzylphosphityl-i-

galactopyranosyl-(14)-2-acetamido-3,6-di-O-benzyl-

2-deoxy-i- -glucopyranoside (70).—Compound 56 (34

D-

D

mg, 0.036 mmol) was dissolved in dry DCM (500 mL)

and 1,2,4-triazole (8 mg) and dibenzyl N,N-di-

ethylphosphoramidite (30 mL, 0.093 mmol) were added.

The mixture was stirred for 15 h, diluted with DCM,

washed successively with sodium bicarbonate, brine,

and water, dried over sodium sulfate and concentrated

under reduced pressure. Column chromatography (10:1

toluene–acetone) resulted in 70 (38 mg, 89%): ¹H NMR

(CDCl₃): l 7.38–7.10 (35 H, Ph), 5.77 (d, 1 H, J 8.1 Hz,

NHAc), 5.60–4.79 (9 H, PhCH₂), 4.70–4.58 (5 H, H-1,

PhCH₂×4), 4.50, 4.42 (d, 1 H, J 11.3 Hz, PhCH₂), 4.45

(d, 1 H, J_1%,2%8.7 Hz, H-1%), 4.42–4.35 (2 H, H-2%,

PhCH₂), 4.01 (dd, 1 H, J_3,4=J_4,57.3 Hz, H-4), 3.94 (d,

1 H, J_3%,4%2.8 Hz, H-4%), 3.91 (dd, 1 H, J_2,3Hz, H-3),

3.85 (dd, 1 H, J_5,6a3.9, J_6a,6b10.5 Hz, H-6a), 3.74 (dt,

1 H, J 6.7, 9.6 Hz, OCH₂CH₂), 3.66 (dd, 1 H, J_5,6b3.9

Hz, H-6b), 3.58–3.52 (2 H, H-2, H-6a%), 3.44–3.38 (4

H, H-3%, H-5, H-5%, H-6b%), 3.36 (dt, 1 H, J 6.8, 9.7 Hz,

OCH₂CH₂), 1.84 (s, 3 H, CH₃, acetate), 1.60–1.50 (2 H,

OCH₂CH₂), 1.30–1.20 (10 H, CH₂, octyl), 0.84 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 170.6 (CO,

acetate), 139.6, 139.4, 139.2, 138.7, 138.6 (aromatic

quat.), 139.1, 139.0 (d, J 4.8 Hz, aromatic quat.), 129.4,

129.1, 129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 128.3,

128.2, 128.1, 128.0 (aromatic CH), 101.9 (C-1%), 100.5

(C-1), 82.5 (C-3%), 78.1 (C-3), 76.2 (C-4), 76.1, 75.4,

75.2, 74.9, 74.8, 74.2, 73.9, 73.7, 73.0 (C-2%, C-5, C-5%,

PhCH₂×5), 70.1 (OCH₂CH₂), 69.7 (C-6), 68.8 (C-6%),

64.6, 64.1 (d, J 8.5 Hz, PhCH₂), 55.1 (C-2) 32.6, 30.3,

30.1, 30.0, 26.7, 23.4 (CH₂, octyl), 24.2 (CH₃, acetate),

Octyl 2-O-phosphono-i-

D-galactopyanosyl-(14)-2-

acetamido-2-deoxy-i- -glucopyranoside disodium salt

D

(8).—Compound 74 (30 mg, 0.025 mmol) was dissolved

in 95% EtOH (2 mL) and 5% palladium-on-charcoal

(12 mg) was added. The mixture was stirred under

hydrogen for 24 h under ambient pressure, ﬁltered,

concentrated, dissolved in water and lyophylized to give

1

8 (10 mg 67%): H NMR (D₂O (0.05 M NaDCO₃/0.045

M NaOD)): l 4.53 (d, 1 H, J_1%,2%7.7 Hz, H-1%), 4.50 (d,

1 H, J_1,28.0 Hz, H-1), 4.05 (dd, 1 H, J_5,6a1.5, J_6a,6b12.7

Hz, H-6a), 3.95 (ddd, 1 H, J_1%,2%7.9, J_2%,3%=J_2%,P9.2 Hz,

H-2%), 3.90 (d, 1 H, J_3%,4%3.5 Hz, H-4%), 3.88 (1 H, H-6b),

3.87 (dt, 1 H, J 6.1, 10.2 Hz, OCH₂CH₂), 3.78 (dd, 1 H,

H-3%), 3.74 (2 H, H-6a%, H-6b%), 3.73 (1 H, H-3), 3.71 (1

H, H-2), 3.70 (1 H, H-4), 3.62 (1 H, H-5), 3.61 (1 H,

H-5), 3.58 (dt, 1 H, J 6.5, 10.3 Hz, OCH₂CH₂), 2.05 (s,

3 H, CH₃, acetate), 1.55–1.50 (2 H, OCH₂CH₂), 1.32–

1.20 (10 H, CH₂, octyl), 0.85 (t, 3 H, J 7.0 Hz, CH₃,

octyl); ¹³C NMR (D₂O (0.05 M NaDCO₃/0.045 M

NaOD)): l 103.5 (C-1%), 102.1 (C-1), 80.6 (C-5%), 75.9

(C-3), 75.7 (C-5), 74.5 (C-2%), 74.4 (C-3%), 73.3 (C-4),

71.2 (OCH₂CH₂), 68.8 (C-4%), 61.7 (C-6%), 60.6 (C-6),

55.2 (C-2), 31.9, 29.6, 29.4, 29.3, 26.0, 22.7 (CH₂, octyl),

23.3 (CH₃, acetate), 14.8 (CH₃, octyl). HRESIMS

Calcd for C₂₂H₄₁NO₁₄Na₂P 620.2060. Found 620.2057.

14.8

C₇₁H₈₄NO₁₃NaP 1212.5578. Found 1212.5578.

Octyl 3,4,6-tri-O-benzyl-2-O-dibenzylphosphono-i-

galactopyranosyl-(14)-2-acetamido-3,6-di-O-benzyl-

2-deoxy-i- -glucopyranoside (74).—Compound 70 (34

(CH₃,

octyl).

HRESIMS

Calcd

for

D-

D

mg, 0.029 mmol) was dissolved in THF (2 mL) and

cooled to −78 °C. To the cooled solution, 30% hydro-

gen peroxide (0.5 mL) was added dropwise. The mix-

ture was warmed to rt, stirred for 2 h, diluted with

DCM, washed successively with sodium thiosulfate,

sodium bicarbonate, and water, dried over sodium sul-

fate and concentrated under reduced pressure. Column

chromatography (10:1 toluene–acetone) resulted in 74

Octyl 2,3,4,6-tetra-O-benzyl-i-

(14)-2-acetamido-3-O-benzyl-2-deoxy-6-O-diben-

zylphosphityl-i- -glucopyranoside (71).—Compound

D-galactopyranosyl-

D

71 (16 mg, 98%) was synthesized from compound 61

(12 mg, 0.013 mmol), 1,2,4-triazole (10 mg), dibenzyl

N,N-diethylphosphoramidite, (30 mL, 0.093 mmol) and

DCM (2 mL), as described for the preparation of 70:

¹H NMR (CDCl₃): l 7.38–7.20 (35 H, Ph), 5.77 (d, 1

H, J 7.7 Hz, NHAc), 5.02–4.59 (9 H, PhCH₂), 4.88 (1

H, J_1,26.8 Hz, H-1), 4.65 (s, 2 H, PhCH₂), 4.58, 4.51,

4.35 (d, 1 H, J 11.2 Hz, PhCH₂), 4.50 (d, 1 H, J_1%,2%7.7

1

(30 mg, 87%): H NMR (CDCl₃): l 7.38–7.20 (35 H,

Ph), 6.60 (bs, 1 H, NHAc), 5.02–4.86 (6 H, PhCH₂),

4.70–4.52 (7 H, H-1, H-2%, PhCH₂×5), 4.44–4.32 (4

H, H-1%, PhCH₂×3), 4.03 (dd, 1 H, J_3,4=J_4,55.9 Hz,

H-4), 3.94 (d, 1 H, J_3%,4%2.8 Hz, H-4%), 3.81 (1 H, H-3),

2150

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

Hz, H-1%), 4.38–4.34 (2 H, H-6a, PhCH₂), 4.13 (m, 1 H,

H-6b), 4.08 (dd, 1 H, J_2,3=J_3,47.8 Hz, H-3), 3.90–3.88

(2 H, H-4, H-4%), 3.78–3.74 (2 H, H-2%, OCH₂CH₂),

3.64 (ddd, 1 H, J_5,6b=J_5,6a4.2, J_4,57.4 Hz, H-5), 3.52

(dd, 1 H, J_6a%,5%=J_6a%,6b%8.2 Hz, H-6a%), 3.44–3.36 (5 H,

H-2, H-3%, H-5%, H-6b%, OCH₂CH₂), 1.82 (s, 3 H, CH₃,

acetate), 1.55–1.45 (2 H, OCH₂CH₂), 1.30–1.20 (10 H,

CH₂, octyl), 0.85 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 170.8 (CO, acetate), 139.6, 139.5,

139.3, 139.2, 138.6 (aromatic quat), 139.0, 136.3 (d, J

6.7 Hz, aromatic quat), 129.1, 129.0, 128.9, 128.8,

128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1 (aromatic

CH), 104.0 (C-1%), 100.2 (C-1), 83.1 (C-3%), 80.7 (C-2%),

77.8 (C-3), 77.4 (C-4), 76.2, 75.4, 74.4, 74.2, 73.9, 73.5

(C-4%, C-5%, PhCH₂×5), 75.7 (d, J_5,P4.9 Hz, C-5), 70.2

(OCH₂CH₂), 68.9 (C-6%), 64.8, 64.7 (d, J 11.0 Hz,

PhCH₂), 62.4 (d, J_6,P10.9 Hz, C-6), 55.9 (C-2) 32.5,

30.2, 30.1, 30.0, 26.7, 23.4 (CH₂, octyl), 24.2 (CH₃,

acetate), 14.8 (CH₃, octyl).

J_1,28.4 Hz, H-1), 4.04 (2 H, H-6a, H-6b), 3.91 (d, 1 H,

J_3%,4%3.5 Hz, H-4%), 3.88 (dt, 1 H, J 5.8, 10.3 Hz,

OCH₂CH₂), 3.81 (dd, 1 H, J_3,4=J_4,59.2 Hz, H-4), 3.79

(1 H, H-3), 3.74 (2 H, H-6a%, H-6b%), 3.71 (1 H, H-2),

3.70 (1 H, H-3%), 3.66 (1 H, H-5%), 3.65 (1 H, H-5), 3.57

(dt, 1 H, J 6.2, 10.2 Hz, OCH₂CH₂), 3.44 (dd, J_2%,3%10.2

Hz, H-2%), 2.05 (s, 3 H, CH₃, acetate), 1.55–1.50 (2 H,

OCH₂CH₂), 1.32–1.20 (10 H, CH₂, octyl), 0.85 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (D₂O (0.05 M

NaDCO₃/0.045 M NaOD)): l 103.5 (C-1%), 102.0 (C-1),

79.0, C-4), 76.2 (C-3), 75.3 (C-5), 74.4 (C-3%), 74.3

(C-5%), 71.8 (C-2%), 71.2 (OCH₂CH₂), 69.5 (C-4%), 62.9

(C-6), 61.9 (C-6%), 55.9 (C-2), 32.5, 30.2, 30.1, 30.0, 26.7,

23.4 (CH₂, octyl), 24.2 (CH₃, acetate), 14.8 (CH₃, oc-

tyl). HRESIMS Calcd for C₂₂H₄₁NO₁₄Na₂P 620.2060.

Found 620.2059.

Octyl 2,3,4,6-tetra-O-benzyl-i-

2-acetamido-6-O-benzyl-2-deoxy-3-O-dibenzylphos-

phityl-i- -glucopyranoside (72).—Compound 72 (15

D-galactosyl-(14)-

D

Octyl 2,3,4,6-tetra-O-benzyl-i-

(14)-2-acetamido-3-O-benzyl-2-deoxy-6-O-diben-

zylphosphono-i- -glucopyranoside (75).—Compound

D

-galactopyranosyl-

mg, 45%) was synthesized from compound 66 (27 mg,

0.029 mmol), 1,2,4-triazole (8 mg), dibenzyl N,N-di-

ethylphosphoramidite, (27 mL, 0.083 mmol) and DCM

(2 mL) as described for the preparation of 70: ¹H NMR

(CDCl₃): l 7.38–7.15 (35 H, Ph), 5.60 (bs, 1 H,

NHAc), 4.88–4.62 (10 H, H-1, PhCH₂×9), 4.58–4.44

(3 H, H-3, PhCH₂×2), 4.40–4.25 (4 H, H-1%,

PhCH₂×3), 3.92 (dd, 1 H, J_3,4=J_4,58.3 Hz, H-4), 3.83

(dd, 1 H, J_5,6a4.3, J_6a,6b10.9 Hz, H-6a), 3.81 (d, 1 H,

J_3%,4%3.3 Hz, H-4%), 3.78 (dt, 1 H, J 6.6, 9.5 Hz,

OCH₂CH₂), 3.72 (dd, 1 H, J_5,6b2.7 Hz, H-6b), 3.67 (dd,

1 H, J_1%,2%7.7, J_2%,3%9.5 Hz, H-2%), 3.55–3.51 (2 H, H-5,

H-6a%), 3.49 (dd, 1 H, J_5%,6b%5.3, J_6a%,6b%9.0 Hz, H-6b%),

3.46–3.38 (2 H, H-2, OCH₂CH₂), 3.35 (dd, 1 H, J_5%,6a%

7.9 Hz, H-5%), 3.32 (dd, 1 H, H-3%), 1.84 (s, 3 H, CH₃,

acetate), 1.60–1.50 (2 H, OCH₂CH₂), 1.30–1.20 (10 H,

CH₂, octyl), 0.84 (t, 3 H, J 7.0 Hz, CH₃, octyl); ¹³C

NMR (CDCl₃): l 171.0 (CO, acetate), 139.5, 139.4,

139.2, 139.1, 138.8 (aromatic quat.), 129.1, 129.0, 128.9,

128.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1

(aromatic CH), 103.7 (C-1%), 100.7 (C-1), 83.1 (C-3%),

80.3 (C-2%), 77.8 (C-4), 76.8 (C-5), 75.9, 75.8, 75.3, 74.1,

74.0, 73.8 (C-4%, C-5, PhCH₂×5), 73.4 (C-3), 70.1

(OCH₂CH₂), 69.3 (C-6), 69.1 (C-6%), 65.1, 65.0

(PhCH₂), 57.3 (C-2) 32.5, 30.2, 30.1, 30.0, 26.7, 23.4

(CH₂, octyl), 24.1 (CH₃, acetate), 14.8 (CH₃, octyl).

HRESIMS Calcd for C₇₁H₈₄NO₁₃NaP 1212.5578.

Found 1212.5552.

D

75 (13 mg, 85%) was synthesized from compound 71

(16 mg, 0.013 mmol), 30% hydrogen peroxide (0.5 mL)

and tetrahyrofuran (2 mL) as described for the prepara-

1

tion of 74: H NMR (CDCl₃): l 7.38–7.20 (35 H, Ph),

5.80 (d, 1 H, J 7.9 Hz, NHAc), 5.02–5.00 (5 H,

PhCH₂), 4.84 (1 H, J_1,26.5 Hz, H-1), 4.78, 4.77, 4.67,

4.64, 4.55, 4.51, 4.27 (d, 1 H, J 11.4 Hz, PhCH₂),

4.43–4.40 (2 H, H-1%, H-6a), 4.36–4.33 (2 H, H-6b,

PhCH₂), 4.05 (dd, 1 H, J_2,3=J_3,47.4 Hz, H-3), 3.88 (d,

1 H, J_3%,4%2.9 Hz, H-4%), 3.83 (dd, 1 H, J_4,57.2 Hz, H-4),

3.78–3.72 (2 H, H-2%, OCH₂CH₂), 3.66 (1 H, H-5),

3.52–3.34 (6 H, H-2, H-3%, H-5%, H-6a%, H-6b%,

OCH₂CH₂), 1.81 (s, 3 H, CH₃, acetate), 1.55–1.42 (2 H,

OCH₂CH₂), 1.28–1.18 (10 H, CH₂, octyl), 0.86 (t, 3 H,

J 7.0 Hz, CH₃, octyl); ¹³C NMR (CDCl₃): l 170.8 (CO,

acetate), 139.6, 139.5, 139.3, 139.2, 138.6 (aromatic

quat), 136.6, 136.3 (d, J_C,P6.1 Hz, aromatic quat.),

129.4, 129.1, 129.0, 128.9, 128.8, 128.7, 128.6, 128.5,

128.4, 128.3, 128.2, 128.1 (aromatic CH), 104.0 (C-1%),

100.2 (C-1), 83.1 (C-3%), 80.5 (C-2%), 77.3 (C-3), 77.0

(C-4), 76.1, 75.4, 74.3, 74.2, 74.1, 73.8, 73.5 (C-4%, C-5%,

PhCH₂×5), 74.7 (d, J_5,P8.5 Hz, C-5), 70.3

(OCH₂CH₂), 69.9, 69.7 (d, J 5.4 Hz, PhCH₂), 68.8

(C-6%), 67.1 (d, J_6,P4.9 Hz, C-6), 55.1 (C-2) 32.5, 30.2,

30.1, 30.0, 26.7, 23.4 (CH₂, octyl), 24.2 (CH₃, acetate),

14.8

C₇₁H₈₄NO₁₄NaP 1228.5527. Found 1228.5516.

Octyl i- -galactopyranosyl-(14)-2-acetamido-2-

deoxy-6-O-phosphono-i- -glucopyranoside disodium

salt (9).—Compound 9 (3 mg, 73%) was synthesized

from compound 75 (8 mg, 6.6×10⁻³mmol), 5% palla-

dium-on-charcoal (9 mg), and 95% EtOH as described

for 8: ¹H NMR (D₂O (0.05 M NaDCO₃/0.045 M

NaOD)): l 4.66 (d, 1 H, J_1%2%8.0 Hz, H-1%), 4.52 (d, 1 H,

(CH₃,

octyl).

HRESIMS

Calcd

for

Octyl 2,3,4,6-tetra-O-benzyl-i-

(14)-2-acetamido-6-O-benzyl-2-deoxy-3-O-diben-

zylphosphono-i- -glucopyranoside (76).—Compound

D-galactopyranosyl-

D

76 (4 mg, 66%) was synthesized from compound 72 (6

mg, 5.0×10⁻³mmol), 30% hydrogen peroxide (0.5

mL) and tetrahyrofuran (2 mL) as described for the

1

preparation of 74: H NMR (CDCl₃): l 7.38–7.05 (35

H, Ph), 5.99 (d, 1 H, J 8.4 Hz, NHAc), 5.10–5.02 (2 H,

PhCH₂), 4.96–4.84 (2 H, PhCH₂), 4.68–4.53 (7 H, H-1,

D. Rabuka, O. Hindsgaul / Carbohydrate Research 337 (2002) 2127–2151

2151

PhCH₂), 4.96–4.84 (2 H, PhCH₂), 4.68–4.53 (7 H, H-1,

H-3, PhCH₂×5), 4.48–4.30 (6 H, H-1%, PhCH₂×5),

4.03 (dd, 1 H, J_3,4=J_4,59.2 Hz, H-4), 3.91 (ddd, 1 H,

(0.05 M NaDCO₃/0.045 M NaOD)): l 102.7 (C-1),

102.0 (C-1%), 76.6 (C-5), 76.0 (C-5%), 74.7 (C-4), 73.6

(C-3%), 73.5 (C-3), 71.3 (OCH₂CH₂), 69.7 (C-4%), 61.8

61.7 (C-6, C-6%), 56.3 (C-2), 31.9, 29.6, 29.4, 29.3, 26.0,

22.7 (CH₂, octyl), 23.3 (CH₃, acetate), 14.8 (CH₃, oc-

tyl). HRESIMS Calcd for C₂₂H₄₁NO₁₄Na₂P 620.2060.

Found 620.2064.

J

_1,2=J_2,NHAc8.2, J_2,310.3 Hz, H-2), 3.88 (dd, 1 H, J_5,6a

3.6, J_6a,6b11.0 Hz, H-6a), 3.83–3.79 (2 H, H-4%,

OCH₂CH₂), 3.66 (dd, 1 H, J_5,6b2.0 Hz, H-6b), 3.62 (dd,

1 H, J_1%,2%7.9, J_2%,3%9.4 Hz, H-2%), 3.50–3.48 (2 H, H-6a%,

H-6b%), 3.42 (dt, 1 H, J 6.7, 9.3 Hz, OCH₂CH₂), 3.39

(ddd, 1 H, H-5), 3.35–3.30 (2 H, H-3%. H-5%), 1.80 (s, 3

H, CH₃, acetate), 1.60–1.50 (2 H, OCH₂CH₂), 1.35–

1.20 (10 H, CH₂, octyl), 0.84 (t, 3 H, J 7.0 Hz, CH₃,

octyl); ¹³C NMR (CDCl₃): l 171.4 (CO, acetate), 139.3,

139.2, 139.1, 139.0, 138.7 (aromatic quat), 137.2, 136.5

(d, J 6.1 Hz, aromatic quat.), 129.1, 129.0, 128.9, 128.8,

128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1 (aromatic

CH), 103.5 (C-1%), 101.8 (C-1), 83.1 (C-3%), 80.1 (C-2%),

78.5 (d, J_3,P6.1 Hz, C-3), 75.9 (C-5), 75.5 (d, J_4,P5.5

Hz, C-4), 75.3, 74.2, 74.1, 74.0, 73.9, 73.5 (C-4%, C-5,

PhCH₂×5), 70.3, 70.2 (d, J 4.3 Hz, PhCH₂), 70.1

(OCH₂CH₂), 69.0 (C-6%), 68.6 (C-6), 56.0 (C-2) 32.5,

30.2, 30.1, 30.0, 26.6, 23.3 (CH₂, octyl), 24.1 (CH₃,

acetate), 14.8 (CH₃, octyl).

Acknowledgements

This work was supported by a grant from the Natu-

ral Sciences and Engineering Research Council of

Canada. We thank Albin Otter for assistance in record-

ing the NMR spectra.

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Octyl i-D-galactopyranosyl-(14)-2-acetamido-2-

deoxy-3-O-phosphono-i-D-glucopyranoside disodium

salt (10).—Compound 10 (1.4 mg, 71%) was synthe-

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1

scribed for the preparation of 8: H NMR (D₂O (0.05

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Article Doi

Synthesis and NMR characterization of the six regioisomeric monophosphates of octyl β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-β-D- glucopyranoside

DOI: 10.1016/S0008-6215(02)00178-7

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Article abstract of DOI:10.1016/S0008-6215(02)00178-7

Full text of DOI:10.1016/S0008-6215(02)00178-7

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