Synthesis of ketopyranosyl glycosides and determination of their anomeric configuration on the basis of the three-bond carbon-proton couplings

Carbohydrate Research 342 (2007) 1393–1404

Synthesis of ketopyranosyl glycosides and determination of their

anomeric conﬁguration on the basis of the three-bond

carbon–proton couplings

a

a,

b

*

´

Gabor Majer, Aniko Borbas, Tunde Zita Illyes, Laszlo Szilagyi,

¨

c

a,d

´

Attila Csaba Benyei and Andras Liptak

^aResearch Group for Carbohydrates of the Hungarian Academy of Sciences, PO Box 94, Debrecen H-4010, Hungary

^bDepartment of Organic Chemistry, PO Box 20, Faculty of Science, University of Debrecen, Debrecen H-4010, Hungary

^cDepartment of Physical Chemistry, PO Box 7, Faculty of Science, University of Debrecen, Debrecen H-4010, Hungary

^dDepartment of Biochemistry, PO Box 55, Faculty of Science, University of Debrecen, Debrecen H-4010, Hungary

Received 9 March 2007; received in revised form 23 April 2007; accepted 6 May 2007

Available online 18 May 2007

Abstract—Anomeric pairs of ketopyranosyl glycosides with various substituents at C_a, C_band C_cwere synthesized from the cor-

responding thioglycosides, and the inﬂuence of the C_a–C_b–C_c–H_ctorsion angle and substituent eﬀects on the three-bond car-

bon–proton couplings was studied. The cis coupling constants range from 1 to 2 Hz. The trans couplings are generally as small

as 2.3–2.6 Hz; however, for compounds bearing an unsubstituted c-carbon, a relatively large trans coupling was measured

(4.8 Hz). An S-ethyl group at the b-position increases the cis coupling (up to 3.2 Hz) compared to the corresponding O-glycosides.

Keywords: Glycosylation; Ketopyranosyl glycosides; Anomeric pairs; Anomeric conﬁguration; Karplus relationship; Three-bond carbon–proton

coupling constant

1. Introduction

A Karplus equation derived from a study of rigid

3

hydrocarbons³predicts J_C,Hvalues ranging from 2.0

Determination of the anomeric conﬁguration of saccha-

rides by NMR methods typically relies on measurements

(60ꢁ) to 9.4 Hz (180ꢁ). In carbohydrates most experi-

mental and theoretical studies apply to C–X–C–H

arrays of bonded atoms (X = O, S, N) typically found

in interglycosidic linkages.⁴C–C–C–H arrays were

investigated, mostly in studies of CH₂OH conforma-

tions at position 6 of aldohexopyranosyl rings.^5–7It is

known, however, that substituent eﬀects may have a

quite dramatic inﬂuence on these couplings. Theoretical

calculations^8–10and experimental studies^10–12indicated

that positive and negative contributions from the oxy-

gen substituents can be as high as 5.0 Hz. Substituent

electronegativities evidently play a role and, very often,

contributions from nonbonded interactions can be

dominant.¹³The latter inﬂuence bond angles and bond

orders and that is why the eﬀect of a particular substitu-

ent is very much dependent also on the site of attach-

ment along the coupling path (a, b or c).^11,13,14In

3

1

of J_H,Hor J_C,Hcouplings for the anomeric protons.

These data are, obviously, unavailable for sugars bear-

ing a quaternary anomeric carbon. Related substances

are ketoses or ulosonic acids such as N-acetyl neurami-

nic acid and KDO. An alternative approach utilizes of

the Karplus-type dependence^1,2of three-bond carbon–

proton couplings (³J_C,H) on the torsion angle between

C_aand H_cin a C_a–C_b–C_c–H_cfragment, where C_cis

the adjacent carbon to the quaternary anomeric C_b. In

practice, this method is expected to provide suﬃcient

results only if H_cis in an axial position.

*

Corresponding author. Fax: +36 52 512900x22342; e-mail:

borbasa@puma.unideb.hu

doi:10.1016/j.carres.2007.05.006

1394

G. Ma´jer et al. / Carbohydrate Research 342 (2007) 1393–1404

addition, the orientation of the electronegative substitu-

ent with respect to the coupled proton has a signiﬁcant

inﬂuence on the J_C,Hvalues. Theoretical calculations,

structure A, R¹= SO₃Et, R²= mono- or disaccharides,

R³= OBn, Fig. 1), which were identiﬁed as a-glycosides

on the basis of the small values of the three-bond cou-

plings between C_aand H_c. The stereochemistry of the

anomeric centre of other ketosides^29–32prepared only

in one of the anomeric forms was also characterized

by the small ³J_Ca,Hcaxcouplings. The literature data^22–24

reported small coupling constants for both of the

anomers thus suggesting that structural assignments

based on a single coupling constant may be dubious or

unreliable. Therefore, we decided to synthesize anomeric

pairs of ketopyranosyl glycosides of the type A and B

(Fig. 1) with various substituents at C_a, C_band C_c, to

test the applicability of the ³J_C,Hvalues for the determi-

nation of anomeric conﬁguration.

3

in agreement with experimental data, have shown that,

3

for example, J_C6,H4is ꢀ2.5 Hz smaller in aldohexo-

pyranoses when the endocyclic oxygen (O5) is anti,

rather than gauche to H4 (2.5–3.5 vs 0.5–1.5 Hz,

respectively).¹⁰

The data published on the C_a–C_b–C_c–H_ctorsion angle

dependence of vicinal carbon–proton couplings in keto-

pyranosyl anomeric pairs^15–24can be divided in two

groups. In the case of KDO or sialic derivatives, these

couplings show signiﬁcant diﬀerences for the

a- and b-anomers. Small couplings were recorded for

the b-anomers (³J_C1,H3axꢀ 1 Hz, synclinal arrangement),

whereas remarkably larger ones for the a-anomers

(³J_C1,H3axꢀ 6 Hz, antiperiplanar arrangement).^15–20

Consequently, the anomeric conﬁguration of KDO or

sialic acid derivatives could be unambiguously deter-

2. Results and discussion

3

mined on the basis of the values of J_C1,H3ax. Similarly,

To study the inﬂuence of the b-substituent on the C_a–H_c

couplings in the case of 1-deoxy-1-ethoxysulfonylheptu-

losides, several anomeric pairs of glycosides were syn-

thesized from thioglycoside 1.²⁶First, methyl and

benzyl glycosides 2a,b and 3a,b were prepared under

conditions that aﬀorded ꢀ1:1 mixtures of the a- and

b-anomers (Scheme 1).

For the synthesis of the ketosyl disaccharides (Scheme

2) methyl 2,3,4-tri-O-benzyl-a-^D-glucopyranoside 4³³

and p-methoxyphenyl 2,3,4-tri-O-benzyl-b-D-glucopyr-

anoside 5 were used as acceptors. (Compound 5 was pre-

pared by the hydrogenolysis of the appropriate

benzylidene acetal³⁴using a LiAlH₄–AlCl₃reagent mix-

ture). Glycosylation of 4 with thioglycoside donor 1 in

the presence of the NIS–TfOH promoter furnished a

mixture of disaccharides 6a and 6b in a 3:1 ratio, and

an elimination product (7) from the donor was also iso-

lated in a 17% yield. Similarly, glycosylation of 5 with

donor 1 resulted in a mixture of anomeric pairs 8a and

8b, together with the elimination product 7.

for ketosyl-azides, -amides, -bromides²¹or C-keto-

3

sides,²⁵distinct J_Ca,Hcaxcouplings could be observed

depending on the orientation of C_a. At the same time,

the sporadic data published for the anomeric pairs of

ketopyranosyl-O-glycosides, other than KDO or sialic

acids, do not show signiﬁcant diﬀerences for the a-

and b-anomers, the vicinal carbon–proton couplings

are small with only ꢀ1 Hz diﬀerences reported for the

syn and anti orientations of C_aand H_c.^22–24

In connection with our previous studies on the sul-

fonic acid mimics of sialyl Lewis X saccharides,^26–28

we prepared hept-2-uloside sulfonic acid mimics (having

H

BnO

H

BnO

α

O

CH₂R¹

OR²

γ

β

R³

OR²

CH₂R¹

α

B

A

To study the eﬀect of charged groups linked to the

a-carbon, sulfonic esters 2a and 2b were converted into

sodium sulfonates 9a and 9b, respectively, by means of

nucleophilic substitution with NaI (Scheme 3).

-

R¹: H, COOEt, SO₃Et, SO₃Na⁺

R²: Me, (glucosyl unit)

R³: OBn, (H)

a-Thioglycoside 12 was prepared from 10³⁵in two

steps involving nucleophilic addition of the ethyl meth-

Figure 1. General structure of the investigated ketopyranosyl glycoside

anomeric pairs.

OBn

O

OBn

O

OBn

SO₃Et

BnO

O

BnO

(i)

OR

+

BnO

OR

SEt

SO₃Et

2a

3a

R = Me

R = Bn

2b

3b

1

˚

Scheme 1. Reagents and conditions: (i) for 2a/b: dry MeOH (15 equiv), NIS (1.2 equiv), TfOH (0.4 equiv), CH₂Cl₂, 3 A MS, ꢁ50 ꢁC, 40 min, 35% of

˚

2a, 47% of 2b; (i) for 3a/b: BnOH (15 equiv), NIS (1.2 equiv), TfOH (0.4 equiv), CH₂Cl₂, 4 A MS, ꢁ50 ꢁC, 20 min, then ꢁ50 to ꢁ 20 ꢁC, 30 min, 64%

of 3a, 21% of 3b.

G. Ma´jer et al. / Carbohydrate Research 342 (2007) 1393–1404

1395

OBn

SO₃Et

O

BnO

O

OBn

O

HO

BnO

6a

8a

R¹

O

BnO

(i)

R¹

BnO

SO₃Et

BnO

1

+

R²

+

BnO

OBn

O

R²

OBn

BnO

O

4 R¹= H, R²= OMe

5 R¹= OPMP, R²= H

7

BnO

EtO₃S

O

BnO

R¹

BnO

6b

8b

R²

6a/b R¹= H, R²= OMe

8a/b R¹= OPMP, R²= H

˚

Scheme 2. Reagents and conditions: (i) for 6a/b: 2 equiv of 4, NIS (1.2 equiv), TfOH (0.8 equiv), CH₂Cl₂, 4 A MS, ꢁ60 ꢁC, 25 min, 37% of 6a, 13%

˚

of 6b, 17% of 7; (i) for 8a/b: 2 equiv of 5, NIS (1.2 equiv), TfOH (0.8 equiv), CH₂Cl₂, 4 A MS, ꢁ50 ꢁC, 25 min, 30% of 8a, 9% of 8b, 32% of 7.

OBn

O

OBn

O

SO₃Na

(i)

H

SO₃Et

(i)

O

BnO

2a

2b

84%

O

BnO

H

OMe

R

9a

9b

10

11 R = OH

12 R = SEt

(ii)

OBn

O

(i)

BnO

(iii)

OMe

OBn

H

90%

OBn

BnO

SO₃Et

H

O

H

BnO

O

SO₃Na

BnO

OCH₃

SO₃Et

+

Scheme 3. Reagents and conditions: (i) NaI (1.1 equiv), acetone, 3 h,

H

OCH₃

reﬂux.

13a

13b

Scheme 4. Reagents and conditions: (i) (i-Pr)₂NH (1.5 equiv), n-BuLi

(1.5 equiv), CH₃SO₃Et (1.5 equiv), ꢁ60 ꢁC to rt, 3 h, 55%; (ii) EtSH

(1.5 equiv), BF₃ÆEt₂O (2.5 equiv), CH₂Cl₂, ꢁ20 ꢁC, 1.5 h, 74%, (iii) dry

anesulfonate anion into the lactone carbonyl of 10 fol-

lowed by BF₃ÆEt₂O-promoted reaction of 11 with ethane-

thiol (Scheme 4). Compound 12 was subsequently

converted into an anomeric mixture of methyl glycosides

13a and 13b, which were suitable for studying the inﬂu-

ence of the lack of a substituent at c-position on the

three-bond couplings.

In addition to the 1-deoxy-1-sulfonatoheptuloside

derivatives, compounds carrying other substituents at

the a-carbon were also synthesized. Nucleophilic addi-

tion of the carbanion generated from ethyl acetate to

aldonolactone 14 gave ethyl 2-deoxy-3-octulosonate

15^36,37as the a-anomer (Scheme 5). The reaction of

the latter with ethanethiol in the presence of BF₃ÆEt₂O

resulted in a-thioglycoside 16, from which methyl glyco-

side (17a/b) was prepared in form of an anomeric mix-

ture in the usual manner. These methyl glycosides

were synthesized recently in a diﬀerent way by Sharma

et al.²⁴by means of radical reactions on the correspond-

ing 1-deoxyenolester.

˚

MeOH (15 equiv), NIS (1.6 equiv), TfOH (0.3 equiv), CH₂Cl₂, 3 A

MS, ꢁ50 ꢁC, 20 min, 57% of 13a, 20% of 13b.

18³⁸using Grignard reaction at ꢁ10 ꢁC (Scheme 6).

Ikegami and co-workers reported the exclusive forma-

tion of methyl a-glycoside 20a³¹directly from 18, using

TMSOTf catalyst. In our hands, this reaction worked

also with stereoselectivity as high as 95%, therefore the

b-anomer could not be isolated this way. Fortunately,

the usual reaction sequence via thioglycoside 19 led to

the formation of both methyl glycosides 20a and 20b,

albeit in low yields.

The structures of the synthesized compounds were

determined by NMR. For 1, 2a, 3a and 12, the anomeric

conﬁguration was conﬁrmed by X-ray diﬀraction

1

measurements. Representative examples of the H-cou-

pled ¹³C NMR spectra are shown in Figure 2.

The three-bond coupling constants between C_aand

H_cfor glycosides 2a,b, 3a,b, 6a,b, 8a,b, 9a,b, 13a,b,

17a,b,²⁴and 20a,b are collected in Table 1.

The synthesis of derivatives having an unsubstituted

a-carbon started from 14, which was converted into

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G. Ma´jer et al. / Carbohydrate Research 342 (2007) 1393–1404

OBn

O

OBn

COOEt

(i)

BnO

O

BnO

O

BnO

OBn

R

14

15 R = OH

16 R = SEt

(ii)

(iii)

OBn

O

OBn

O

COOEt

BnO

OMe

+

BnO

OMe

COOEt

17a

17b

Scheme 5. Reagents and conditions: (i) (i-Pr)₂NH (1.5 equiv), n-BuLi

(1.5 equiv), EtOAc (1.5 equiv), THF, ꢁ60 ꢁC to rt, 1 h, 66%; (ii) EtSH

(1.5 equiv), BF₃ÆEt₂O (2.5 equiv), CH₂Cl₂, 0 ꢁC, overnight, 63%; (iii)

dry MeOH (15 equiv), NIS (1.2 equiv), TfOH (0.4 equiv), CH₂Cl₂, 3 A

MS, ꢁ50 ꢁC, 25 min, 22% of 17a, 31% of 17b.

˚

Figure 2. ¹H-coupled ¹³C NMR spectra of compounds 13a and 13b,

showing the triplet of the a-carbon. Additional splitting arises from

coupling to the c-proton. Asterisks identify peaks from a minor

impurity.

OBn

(i)

O

BnO

CH₃

14

Table 1. Three-bond carbon–proton couplings, and chemical shifts of

the anomeric carbons for the anomeric pairs of O-glycosides

BnO

R

Compound

³J_Ca,Hc(Hz)

d C_b(ppm)

18 R = OH

19 R = SEt

2a^a

2b

ꢀ1 cis

99.00

101.00

95.73

100.22

99.10

100.80

99.09

100.48

100.79

101.30

97.78

(ii)

2.4 trans

61 cis

3a^a

3b

(iii)

OBn

2.3 trans

61 cis

OBn

O

6a

6b

O

BnO

OMe

CH₃

2.5 trans

ꢀ2 cis

CH₃

OMe

+

8a

8b

BnO

n.a.

9a

9b

61 cis

20a

20b

2.4 trans

61 cis

Scheme 6. Reagents and conditions: (i) CH₃MgI (1.3 equiv), dry Et₂O,

ꢁ10 ꢁC, 15 min, 84%; (ii) EtSH (1.5 equiv), BF₃ÆEt₂O (2.5 equiv),

CH₂Cl₂, 0 ꢁC, 4.5 h, 30%; (iii) dry MeOH (15 equiv), NIS (1.2 equiv),

TfOH (0.4 equiv), CH₂Cl₂, 3 A MS, ꢁ50 ꢁC, 20 min, 25% of 20a, 18%

13a

13b

17a

17b

20a

20b

4.8 trans

ꢀ1 cis

98.12

101.10

101.50

100.20

102.00

˚

2.6 trans

1.8 cis

of 20b.

2.6 trans

^aStructures have been veriﬁed by X-ray measurements.

Comparing the values for the anomeric pairs we ﬁnd

that, in agreement with our previous data,^26–28these cou-

plings tend to be small: ꢂ1 Hz and ꢂ2.5 Hz, respectively,

for the syn and anti relationship between the coupled

nuclei (C_aand H_c). This trend is quite consistent for

derivatives carrying an electron withdrawing substituent

(such as SO₃Et: 2a/2b, 3a/3b, 6a/6b; SO₃^ꢁ: 9a/9b;

COOEt: 17a/17b) attached to the a-carbon and oxygen

substituents at both of the b- and c-carbon. However,

the coupling constant for compound 8a is surprisingly

high (ꢀ2 Hz). At the same time, the size of the group

attached to the b-carbon does not seem to play a role

because very similar couplings are observed in monosac-

charides (2a,b, 3a,b), and in the respective disaccharides

(6a/b) or trisaccharides^26–28(i.e., when the substituent

of the b-carbon is a diglycosyl unit), as well.

For compounds bearing unsubstituted a- (20a³¹and

20b) or c-carbons (13a,b) and oxygen at the b position,

the cis-coupling is similarly small [e.g., <1 Hz for 13a,

and slightly larger (1.8 Hz) for 20a]. The magnitude of

the trans-coupling is, however, diﬀerent, depending on

the position of the substituent. We measured a relatively

large coupling (4.8 Hz) with an electronegative group

(SO₃Et) at the a position (13b) and a signiﬁcantly smal-

ler one (2.6 Hz) in a c-substituted (with OBn) trans-

derivative (20b). This is a manifestation of the inﬂuence

of the position of the substituent along the coupling

path.^2,10,11,14Furthermore, this example shows that the

substituent eﬀect is also dependent on the relative spatial

disposition of the coupled nuclei (a substitution exerting

G. Ma´jer et al. / Carbohydrate Research 342 (2007) 1393–1404

1397

a signiﬁcant eﬀect on the trans coupling and a negligible

one on the cis coupling); this may be due to nonbonded/

steric interactions between the substituents.¹The eﬀect

of the relative disposition of the oxygen at the b-carbon

was shown to be signiﬁcant even when the torsion angle

between the coupled nuclei is the same.¹⁰

Inspection of the chemical shifts of the anomeric car-

bons (C_b) for the anomeric O-glycoside pairs (Table 1)

indicates weak correlation between these shifts and the

anomeric conﬁguration; the shifts for b-glycosides are

usually smaller than for their a-counterparts. The diﬀer-

ence is, however, on the order of 1 ppm or less (except

for 3a vs 3b); therefore, this correlation has very limited

diagnostic value.

Because of our interest in the 1-sulfonylheptulose

derivatives, the three-bond coupling constants between

C_aand H_cfor thioglycosides 1 and 12, for the anomeric

OH-derivatives 11 and 21²⁶and also for glycosyl azide

22 (prepared from 21 using trimethylsilyl azide in the

presence of a Lewis acid, Scheme 7) were measured.

These compounds could be synthesized only as a-ano-

mers, the stereochemistry of the anomeric centre for 1

and 12 was also determined by X-ray measurements

(an ORTEP view of compound 12 is shown in Fig. 3).

The three-bond coupling constants between C_aand H_c

for compounds 1, 11, 12, 21 and 22 are collected in

Table 2.

It is seen that an S-ethyl group at the b position

increases the cis coupling in the a-substituted derivatives

irrespective of whether the c-carbon bears an electro-

negative group or not (1 and 12, respectively). Because

the eﬀects of OH- or azido groups are only moderate,

the cis coupling constants range from 1.7 to 2.2 Hz in

11, 21 and 22, compared to the usual ꢀ1 Hz values of

the O-alkyl derivatives. The eﬀect of the same group

on the trans coupling could not be tested because of

the lack of compounds with an opposite (i.e., b-) ano-

meric conﬁguration.

Figure 3. ORTEP view of compound 12.

Table 2. Three-bond carbon–proton couplings, and chemical shifts of

the anomeric carbons of the a-glycosides

Compound

³J_Ca,Hc(Hz)

d C_b(ppm)

1^a

2.7

2.2

3.2

2.1

1.7

89.70

94.86

84.48

95.73

92.92

11

12^a

21

22

^aStructures have been veriﬁed by X-ray measurements.

with diﬀerent substituents and/or diﬀerent substitution

patterns along the coupling path are, however, unreli-

able and, therefore, discouraged. In such cases it is rec-

ommended to seek independent structural evidence such

as NOEs, chemical shifts or X-ray determination.

On the basis of these results, it should be concluded

that application of three-bond carbon–proton couplings

for assigning the anomeric conﬁgurations of sugars with

quaternary anomeric carbon centres requires caution.

When both anomers of a particular derivative are avail-

3. Experimental

Optical rotations were measured at room temperature

with a Perkin–Elmer 241 automatic polarimeter. Melt-

ing points were determined on a Cole-Palmer hot-stage

apparatus and are uncorrected. TLC was performed

on Kieselgel 60 F₂₅₄(Merck) with detection by charring

with 50% aqueous sulfuric acid. Column chromatogra-

phy was performed on Silica Gel 60 (E. Merck, 0.063–

0.200 mm). The organic solutions were dried over

3

able it is likely that of the two measured J_C,H’s the lar-

ger one indicates trans arrangement of the coupled

nuclei. Structural assignments based on a single cou-

pling constant or from data measured on derivatives

OBn

O

OBn

O

SO₃Et

BnO

1

(i)

MgSO₄and concentrated in vacuo. The H (200, 360

and 500 MHz) and ¹³C NMR (50, 90 and 125 MHz)

spectra were recorded with Bruker AC-200, AM-360

and DRX-500 Avance spectrometers in CDCl₃solutions

and in CD₃OD (for 9a/b). Chemical shifts are referenced

BnO

OH

N₃

21

22

Scheme 7. Reagents and conditions: (i) Me₃SiN₃(1.2 equiv), BF₃ÆEt₂O

(2 equiv), CH₂Cl₂, rt, 3 h, 78%.

1

to Me₄Si (0.00 ppm for H) or to the residual solvent

1398

G. Ma´jer et al. / Carbohydrate Research 342 (2007) 1393–1404

signals (77.00 ppm or 49.05 ppm for ¹³C). The ¹³C/¹H

long-range coupling constants were measured from

¹H-coupled ¹³C NMR spectra at 125 MHz.

added. When TLC showed complete conversion of the

starting material, the solution was diluted with dichloro-

methane, extracted with water until neutral and the

organic layer was dried and evaporated. The crude

residue was puriﬁed by column chromatography.

X-ray diﬀraction data were collected at 293 (1) K,

Enraf Nonius MACH3 diﬀractometer, Mo Ka radiation

˚

k = 0.71073 A. The structure was solved using the

SIR-92 software³⁹and reﬁned on F²using SHELX-97 pro-

gram,⁴⁰publication material was prepared with the

WINGX-97 suite.⁴¹Complete crystallographic data for

the structural analysis have been deposited with the

Cambridge Crystallographic Data Centre, CCDC No.

621975–621978. Copies of this information may be

obtained free of charge from the Director, Cambridge

Crystallographic Data Centre, 12 Union Road, Cam-

bridge, CB2 1EZ, UK. (fax: +44-1223-336033, e-mail:

deposit@ccdc.cam.ac.uk or via: www.ccdc.cam.ac.uk).

MALDI-TOF MS analyses of the compounds were car-

ried out in the positive reﬂectron mode using a BIFLEX

III mass spectrometer (Bruker, Germany) equipped with

delayed-ion extraction. The 2,4,6-trihidroxy-aceto-

phenone (THAP) matrix solution was saturated THAP

solution in MeCN.

3.4. Methyl 3,4,5,7-tetra-O-benzyl-1-deoxy-1-ethoxy-

sulfonyl-a-^D-gluco-hept-2-ulopyranoside (2a) and methyl

3,4,5,7-tetra-O-benzyl-1-deoxy-1-ethoxysulfonyl-b-^D-

gluco-hept-2-ulopyranoside (2b)

Donor 1²⁶(1.00 g, 1.41 mmol) was converted by method

A to give a mixture of 2a and 2b. The anomers were sep-

arated by column chromatography using CH₂Cl₂–ace-

tone (98:2). Compound 2a was isolated as white

crystals (330 mg, 35%): mp 88 ꢁC (ethyl-acetate–n-hex-

ane); [a]_D+35.3 (c 0.3, CHCl₃); R_f= 0.57 (n-hexane–

1

EtOAc, 6:4); H NMR (200 MHz, CDCl₃): d 7.39–7.27

(m, 20H, Ph), 5.03 (d, 1H, J = 11.0 Hz, CH₂Ph), 4.94

(s, 2H, CH₂Ph), 4.88 (d, 1H, J = 10.5 Hz, CH₂Ph),

4.84 (d, 1H, J = 11.0 Hz, CH₂Ph), 4.65 (d, 1H,

J = 12.0 Hz, CH₂Ph), 4.63 (d, 1H, J = 10.5 Hz, CH₂Ph),

4.56 (d, 1H, J = 12.0 Hz, CH₂Ph), 4.32–4.00 (m, 4H),

3.85–3.66 (m, 4H), 3.58 (s, 2H), 3.29 (s, 3H, OCH₃),

1.26 (t, 3H, J = 7.1 Hz, OCH₂CH₃); ¹³C NMR

(50 MHz, CD₃OD): d 138.5, 138.2, 138.1, 138.0 (4C-

quat. Ph), 128.4–127.5 (20C, Ph), 99.1 (C-2), 83.2,

79.8, 78.1 (C-3, C-4, C-5), 75.6, 75.5, 75.2, 73.4

(4CH₂Ph), 73.1 (C-6), 68.7, 67.6 (SO₃CH₂CH₃, C-7),

50.5 (C-1), 48.0 (OCH₃), 15.2 (SO₃CH₂CH₃). Anal.

Calcd for C₃₈H₄₄O₉S: C, 67.43; H, 6.55. Found: C,

67.52; H, 6.46. Compound 2b was isolated as a syrup

(445 mg, 47%): [a]_D+40.6 (c 0.3, CHCl₃); R_f= 0.74 (n-

hexane–EtOAc, 6:4); ¹H NMR (200 MHz, CDCl₃): d

7.39–7.21 (m, 20H, Ph), 4.89 (d, 1H, J = 11.2 Hz,

CH₂Ph), 4.89–4.62 (m, 6H, CH₂Ph), 4.53 (d, 1H,

J = 12 Hz, CH₂Ph), 4.31 (q, 2H, J = 7.0 Hz,

SO₃CH₂CH₃), 4.12–4.02 (m, 2H), 3.91–3.69 (m, 5H),

3.63 (d, 1H, J = 15.0 Hz, H-1b), 3.46 (s, 3H, OCH₃),

1.40 (t, 3H, J = 7.0 Hz, SO₃CH₂CH₃); ¹³C NMR

(50 MHz, CD₃OD): d 138.3, 138.2 (2·), 137.6 (4C-quat.

Ph), 128.4–127.5 (20C, Ph), 100.2 (C-2), 83.0, 78.6, 77.0

(C-3, C-4, C-5) 74.2, 74.0 (2CH₂Ph), 73.8 (C-6), 73.3

(CH₂Ph), 68.6, 66.8 (SO₃CH₂CH₃, C-7), 51.2 (C-1),

48.8 (OCH₃), 15.1 (SO₃CH₂CH₃). Anal. Calcd for

C₃₈H₄₄O₉S: C, 67.43; H, 6.55. Found: C, 67.49; H, 6.49.

3.1. General method A for the formation of methyl

glycosides (2a/b, 13a/b, 17a/b, 20a/b)

To a solution of thioglycoside donor (1 mmol) in

˚

CH₂Cl₂(10 mL/g) were added successively 3 A molecu-

lar sieves (1–1.5 g/g) and dry MeOH (610 lL, 15 equiv),

and the mixture was stirred at rt for 3 h. The mixture

was then cooled to ꢁ50 ꢁC and a solution of 1.2 equiv

of NIS and 0.4 equiv of TfOH in dry THF was added.

The mixture was kept at ꢁ50 ꢁC until the TLC showed

complete conversion of the donor (20–30 min). The

reaction was quenched by addition of 139 lL (2 equiv)

of Et₃N. Insoluble materials were removed by ﬁltration,

the ﬁltrate was diluted with CH₂Cl₂, extracted three

times with water, dried and evaporated. The residue

was then puriﬁed by column chromatography.

3.2. General method B for the cleavage of sulfonic esters

by sodium-iodide (9a, 9b)

To a solution of protected ethoxysulfonyl-derivative

(1 mmol) in acetone (20 mL/g), 1.2 equiv (1.2 mmol) of

NaI was added, and the solution was heated at reﬂux

for 2 days. The mixture was evaporated, the crude yel-

low residue was puriﬁed by column chromatography

using CH₂Cl₂–methanol (85:15).

3.5. Benzyl 3,4,5,7-tetra-O-benzyl-1-deoxy-1-ethoxy-

sulfonyl-a-^D-gluco-hept-2-ulopyranoside (3a) and benzyl

3,4,5,7-tetra-O-benzyl-1-deoxy-1-ethoxysulfonyl-b-^D-

gluco-hept-2-ulopyranoside (3b)

3.3. General method C for the formation of thioglycosides

(12, 16, 19)

To a solution of 1 (750 mg 1.06 mmol) in dry CH₂Cl₂

(10 mL) BnOH (1.65 mL, 15.9 mmol, 15 equiv) was

added, then the reaction was carried out and worked

up according to method A to give a mixture of 3a and

To a solution of compound 11, 15 or 18 in dry CH₂Cl₂

(10 mL/g) ethanethiol (1.5 equiv) was added, and the

mixture was cooled before BF₃ÆEt₂O (2.5 equiv) was

G. Ma´jer et al. / Carbohydrate Research 342 (2007) 1393–1404

1399

3b. The anomers were separated by column chromatog-

raphy using n-hexane–EtOAc (7:3). Compound 3a was

isolated as white crystals (510 mg, 66%): mp 108–

110 ꢁC (ethyl acetate–n-hexane); [a]_D+54.2 (c 0.2,

CHCl₃); R_f= 0.35 (n-hexane–EtOAc, 7:3); ¹H NMR

(200 MHz, CDCl₃): d 7.39–7.15 (m, 25H, Ph), 5.06 (d,

1H, J = 11.5 Hz, CH₂Ph), 4.9 (s, 3H, CH₂Ph), 4.85 (d,

1H, J = 11.5 Hz, CH₂Ph), 4.67–4.51 (m, 5H, CH₂Ph),

4.30 (d, 1H, J = 9.5 Hz), 4.26–4.11 (m, 3H), 3.82–3.67

(m, 4H), 3.63 (d, 1H, J = 15.5 Hz, H-2a), 3.55 (d, 1H,

J = 15.5 Hz, H-2b), 1.22 (t, 3H, J = 7.0 Hz,

SO₃CH₂CH₃); ¹³C NMR (50 MHz, CD₃OD): d 138.5,

138.3, 138.0, 137.4 (4C-quat. Ph), 128.6–26.8 (25C,

Ph), 99.6 (C-2), 83.0, 80.0, 78.2 (C-3, C-4, C-5), 75.4,

75.1 (2·), 73.3 (4CH₂Ph), 73.3 (C-6), 68.7, 67.5 (C-7,

SO₃CH₂CH₃), 62.4 (CH₂Ph-aglycon), 51.7 (C-1), 15.1

(SO₃CH₂CH₃). Anal. Calcd for C₄₄H₄₈O₉S: C, 70.19;

H, 6.43. Found: C, 70.11; H, 6.51. Compound 3b was

isolated as a syrup (166 mg, 22%): [a]_D+22.7 (c 0.2,

CHCl₃); R_f= 0.39 (n-hexane–EtOAc, 7:3); ¹H NMR

(500 MHz, CDCl₃): d 7.48–7.13 (m, 25H, Ph) 4.84–

4.75 (m, 5H, CH₂Ph), 4.72 (s, 1H, CH₂Ph), 4.69 (d,

1H, J = 10.8 Hz, CH₂Ph), 4.61 (d, 1H, J = 10.8 Hz,

CH₂Ph), 4.60 (d, 1H, J = 12.0 Hz, CH₂Ph), 4.50 (d,

1H, J = 12.0 Hz, CH₂Ph), 4.27–3.49 (m, 10H), 1.19 (t,

3H, J = 7.0 Hz, SO₃CH₂CH₃); ¹³C NMR (50 MHz,

CD₃OD): d 138.3, 138.2, 138.1, 137.8, 137.6 (5 C-quat.

Ph), 128.4–127.2 (25C, Ph), 100.2 (C-2), 83.2, 79.2,

76.8 (C-3, C-4, C-5), 74.6 (CH₂Ph), 73.8 (C-6), 73.7,

73.5, 73.4, 72.1 (4CH₂Ph), 68.6, 66.8 (SO₃CH₂CH₃, C-

7), 63.2 (CH₂Ph-aglycon), 51.4 (C-1), 14.9

(SO₃CH₂CH₃). Anal. Calcd for C₄₄H₄₈O₉S: C, 70.19;

H, 6.43. Found: C, 70.27; H, 6.35.

then 6a and 6b were separated using n-hexane–EtOAc

(8:2). Compound 6a²⁷(272 mg, 49%): [a]_D+58.7 (c

0.5, CHCl₃), lit.²⁷+55.4 (c 3.6, CHCl₃); R_f= 0.48

(CH₂Cl₂–acetone, 98:2) and 0.24 (n-hexane–EtOAc

8:2). Anal. Calcd for C₆₅H₇₂O₁₄S: C, 70.38; H, 6.54.

Found: C, 70.46; H, 6.46. Compound 6b (94 mg, 17%):

[a]_D+20.9 (c 0.7, CHCl₃); R_f= 0.48 (CH₂Cl₂–acetone,

98:2) and 0.30 (n-hexane–EtOAc, 8:2); ¹H NMR

(500 MHz, CDCl₃): d 7.32–7.14 (m, 35H, Ph), 4.97 (d,

1H, J = 11.0 Hz, CH₂Ph), 4.96 (d, 1H, J = 10.9 Hz,

CH₂Ph), 4.92–4.85 (m, 4H, CH₂Ph), 4.78 (d, 1H,

J = 11.0 Hz, CH₂Ph), 4.77 (d, 1H, J = 10.2 Hz, CH₂Ph),

4.74 (d, 1H, J = 11.6 Hz, CH₂Ph), 4.72 (d, 1H,

J = 10.8 Hz, CH₂Ph), 4.59 (d, 1H, J = 12.2 Hz, CH₂Ph),

4.55 (d, 1H, J = 10.7 Hz, CH₂Ph), 4.53 (d, 1H,

J = 12.1 Hz, CH₂Ph), 4.49 (d, 1H, J = 3.5 Hz), 4.36 (d,

1H, J = 12.15 Hz, CH₂Ph), 4.23 (q, 2H, J = 7.1 Hz,

SO₃CH₂CH₃), 4.16–4.09 (m, 1H), 4.01–3.95 (m, 3H),

3.89–3.82 (m, 5H), 3.76–3.73 (m, 2H), 3.65 (t, 1H,

J = 8.0 Hz), 3.57 (d, 1H, J = 15.3 Hz, H-1b⁰), 3.49 (dd,

1H, J = 3.5, 9.6 Hz), 3.31 (s, 3H, OCH₃), 1.32 (t, 3H,

J = 7.1 Hz, SO₃CH₂CH₃); ¹³C NMR (50 MHz,

CD₃OD): d 139.0, 138.9, 138.3, 138.2, 138.2, 138.0,

138.0 (7C-quat. Ph), 128.4–127.3 (35C, Ph), 100.8 (C-

2⁰), 98.0 (C-1), 83.4, 82.1, 79.9, 78.7, 77.2, 77.1 (C-2,

C-3, C-4, C-3⁰, C-4⁰, C-5⁰), 75.6, 74.8, 74.7, 74.7

(4CH₂Ph), 74.0 (C-5 or C-6⁰), 73.7, 73.3 (2·) (3CH₂Ph),

69.8 (C-5 or C-6⁰), 68.8 (SO₃CH₂CH₃), 66.4, 59.9 (C-6,

C-7⁰), 55.0 (OCH₃), 51.3 (C-1⁰), 15.1 (SO₃CH₂CH₃).

Anal. Calcd for C₆₅H₇₂O₁₄S: C, 70.38; H, 6.54. Found:

C, 70.49; H, 6.43. Compound 7²⁷was isolated as a syrup

(55 mg, 17%): [a]_D+67.7 (c 0.6, CHCl₃), lit.²⁷+64.1 (c

0.23, CHCl₃); R_f= 0.58 (CH₂Cl₂–acetone, 98:2).

3.6. Methyl 2,3,4-tri-O-benzyl-6-O-(3,4,5,7-tetra-O-benz-

yl-1-deoxy-1-ethoxysulfonyl-a-^D-gluco-hept-2-ulopyran-

osyl)-a-^D-glucopyranoside (6a) and methyl 2,3,4-tri-O-

benzyl-6-O-(3,4,5,7-tetra-O-benzyl-1-deoxy-1-ethoxy-

sulfonyl-b-^D-gluco-hept-2-ulopyranosyl)-a-D-glucopyr-

anoside (6b) and 2,6-anhydro-3,4,5,7-tetra-O-benzyl-1-

ethoxysulfonyl-a-^D-gluco-hept-1-enitol (7)

3.7. p-Methoxyphenyl 2,3,4-tri-O-benzyl-6-O-(3,4,5,7-

tetra-O-benzyl-1-deoxy-1-ethoxysulfonyl-a-^D-gluco-hept-

2-ulopyranosyl)-b-^D-glucopyranoside (8a) and p-meth-

oxyphenyl 2,3,4-tri-O-benzyl-6-O-(3,4,5,7-tetra-O-benz-

yl-1-deoxy-1-ethoxysulfonyl-b-^D-gluco-hept-2-ulopyran-

osyl)-b-^D-glucopyranoside (8b) and 2,6-anhydro-3,4,5,7-

tetra-O-benzyl-1-ethoxysulfonyl-a-^D-gluco-hept-1-enitol

(7)

To a solution of 1 (375 mg, 0.50 mmol, 1 equiv) and 4³³

(465 mg, 1.00 mmol, 2 equiv) in dry CH₂Cl₂(15 mL)

were added 4 A molecular sieves (1.0–1.5 g) and the mix-

To a solution of 1 (424 mg, 0.60 mmol, 1 equiv) and 5

˚

(500 mg, 0.90 mmol, 1.5 equiv) in dry CH₂Cl₂(15 mL)

˚

ture was stirred overnight. Then it was cooled to ꢁ50 ꢁC

and a solution of 1.2 equiv of NIS and 0.4 equiv of

TfOH in dry THF was added. The mixture was kept

at ꢁ50 ꢁC until the TLC showed the complete conver-

sion of the donor compound (1h). The reaction was

quenched by addition of 70 lL (2 equiv) of Et₃N. Insol-

uble materials were removed by ﬁltration, the ﬁltrate

was diluted with CH₂Cl₂, extracted three times with

water, dried and evaporated. The residue was then puri-

ﬁed by chromatography. First, the mixture of 6a and 6b

were separated from 7 using CH₂Cl₂–acetone (98:2),

were added 4 A molecular sieves (1.0–1.5 g) and the mix-

ture was stirred overnight. Then it was cooled to ꢁ50 ꢁC

and a solution of 1.2 equiv of NIS and 0.4 equiv of TfOH

in dry THF was added. The mixture was kept at ꢁ50 ꢁC

until the TLC showed the complete conversion of the

donor compound (40 min). The reaction was quenched

by addition of Et₃N (83 lL, 1.20 mmol, 2.00 equiv).

Insoluble materials were removed by ﬁltration, the ﬁl-

trate was diluted with CH₂Cl₂, extracted three times with

water, dried and evaporated. The residue was then puri-

ﬁed by chromatography using CH₂Cl₂–acetone (98:2) to

1400

G. Ma´jer et al. / Carbohydrate Research 342 (2007) 1393–1404

aﬀord the pure 7 and a mixture of 8a and 8b which were

separated using n-hexane–EtOAc (7:3). Compound 8a

(214 mg, 30%): [a]_D+27.6 (c 0.1, CHCl₃); R_f= 0.53

92:8); ¹H NMR (200 MHz, CDCl₃): d 7.27–7.04 (m,

20H, Ph), 4.76–4.33 (m, 8H, CH₂Ph), 4.52–4.33 (m,

8H), 3.39 (s, 3H, OCH₃); ¹³C NMR (50 MHz, CDCl₃):

d 138.3, 138.2, 138.1, 138.1 (4C-quat. Ph), 128.4–127.5

(20C, Ph), 100.8 (C-2), 83.0, 78.1, 77.4 (C-3, C-4, C-5),

74.4, 73.5, 73.1 (3CH₂Ph), 73.0 (C-6), 72.7 (CH₂Ph),

68.7 (C-7), 50.8 (C-1), 49.0 (OCH₃). Anal. Calcd for

C₃₆H₃₉NaO₉S: C, 64.46; H, 5.86. Found: C, 64.39; H,

5.93.

1

(CH₂Cl₂–acetone, 98:2); H NMR (500 MHz, CDCl₃):

d 7.40–7.19 (m, 35H, Ph), 7.01, 6.68 (2m, each 2H,

PMP-arom.), 5.07–4.49 (m, 14H, CH₂Ph), 4.26–3.05

(m, 17H), 3.52 (s, 3H, OCH₃), 1.14 (t, 3H, J = 7.1 Hz,

OCH₂CH₃); ¹³C NMR (125 MHz, CD₃OD): d 155.5,

151.3 (C-quat. PMP), 138.6, 138.4 (3·), 138.2, 138.1,

137.9 (7C-quat. Ph), 128.5–127.2 (35C, Ph.), 119.1,

114.7 (4C-arom. PMP), 103.4 (C-1), 99.1 (C-2⁰), 84.4,

82.9, 82.0, 80.0, 78.1, 77.8 (C-2, C-3, C-4, C-3⁰, C-4⁰,

C-5⁰), 75.6, 75.3, 75.0 (3·), 74.9 (6 CH₂Ph), 73.5 (C-5

or C-6⁰), 73.0 (CH₂Ph), 72.9 (C-5 or C-6⁰), 68.6

(SO₃CH₂CH₃), 67.4, 60.2 (C-6, C-7⁰), 55.3 (OCH₃),

51.5 (C-1⁰), 15.0 (SO₃CH₂CH₃); MALDIMS: m/z calcd

for C₇₁H₇₆NaO₁₅S⁺[M+Na]⁺: 1223.48; found,

1223.48. Compound 8b (64 mg, 9%): [a]_D+8.6 (c 0.2,

CHCl₃); R_f= 0.45 (CH₂Cl₂–acetone, 98:2); ¹³C NMR

(125 MHz, CD₃OD): d 155.0, 151.3 (2C-quat. PMP),

138.9, 138.8, 138.3, 138.3 (3·), 137.9 (7C-quat. Ph),

117.4, 114.6 (4C-arom. PMP), 101.9 (C-1), 100.5 (C-2⁰),

84.6, 83.2, 81.8, 78.9, 77.3, 76.6 (C-2, C-3, C-4, C-3⁰, C-

4⁰, C-5⁰), 75.6, 74.9, 74.8 (3CH₂Ph), 74.3, 74.0 (C-5, C-

6⁰), 73.8, 73.3, 73.1 (3CH₂Ph), 69.5 (SO₃CH₂CH₃),

66.6, 59.6 (C-6, C-7⁰), 55.6 (OCH₃), 51.5 (C-1⁰), 15.0

3.10. 4,5,7-Tri-O-benzyl-1,3-dideoxy-1-ethoxysulfonyl-a-

D-arabino-hept-2-ulopyranose (11)

A solution of (i-Pr)₂NH (2.16 mL, 1.50 mmol, 1.5 equiv)

in dry THF (10 mL) was treated with 2.5 M n-BuLi in n-

hexane (6.17 mL, 1.50 mmol, 1.5 equiv) at ꢁ15 ꢁC under

argon atmosphere. After 15 min the solution was cooled

to ꢁ60 ꢁC and CH₃SO₃Et (1.64 mL, 1.5 mmol,

1.5 equiv) was added. The mixture was kept at ꢁ60 ꢁC

for 15 min, and then aldonolactone derivative 10³⁵

(4.45 g, 10.03 mmol) was added. The mixture was kept

at ꢁ60 ꢁC for 1 h, then it was allowed to warm up to

rt, and concentrated. The residue was diluted with

CH₂Cl₂and was extracted with water until neutral, then

dried and evaporated. The residue was puriﬁed by col-

umn chromatography using CH₂Cl₂–acetone (97:3) to

aﬀord 11 (3.14 g, 88%): [a]_D+27.9 (c 0.2, CHCl₃);

(SO₃CH₂CH₃);

MALDI-MS:

m/z

calcd

for

C₇₁H₇₆NaO₁₅S⁺[M+Na]⁺: 1223.48. Found: 1223.48.

R_f= 0.46

(CH₂Cl₂–acetone,

97:3);

¹H

NMR

Compound 7 was isolated in a 32% yield (123 mg).

(200 MHz, CDCl₃): d 7.34–7.18 (m, 15H, Ph), 4.89 (d,

1H, J = 10.9 Hz, CH₂Ph), 4.67 (d, 1H, J = 11.9 Hz,

CH₂Ph), 4.62 (s, 1H, CH₂Ph), 4.56 (d, 1H,

J = 11.1 Hz, CH₂Ph), 4.55 (s, 1H, CH₂Ph), 4.49 (d,

1H, J = 12.1 Hz, CH₂Ph), 4.29 (q, 2H, J = 7.1 Hz,

SO₃CH₂CH₃), 4.17–4.01 (m, 2H), 3.82–3.51 (m, 5H),

2.6–2.31 (m, 4H, SCH₂CH₃, H-2a, H-2b), 1.29 (t, 3H,

J = 7.1 Hz, SCH₂CH₃), 1.20 (t, 3H, J = 7.5 Hz,

3.8. Methyl 3,4,5,7-tetra-O-benzyl-1-deoxy-1-sodium-

sulfonato-a-^D-gluco-hept-2-ulopyranoside (9a)

Compound 2a (160 mg, 0.24 mol) was converted by

method B to give compound 9a (136 mg, 84%): R_f0.26

1

(CH₂Cl₂–MeOH 92:8); H NMR (200 MHz, CD₃OD):

d 7.42–7.41 (m, 20H, Ph), 5.02 (d, 1H, J 10.7 Hz,

CH₂Ph), 4.88 (d, 1H, J 10.8 Hz, CH₂Ph), 4.87 (s, 2H,

CH₂Ph), 4.84 (s, 2H, CH₂Ph), 4.75 (d, 1H, J 11.0 Hz,

CH₂Ph), 4.73 (d, 1H, J 12.2 Hz, CH₂Ph), 4.62 (d, 1H,

J 12.3 Hz, CH₂Ph), 4.54 (s, 1H, CH₂Ph), 4.49 (s, 1H,

CH₂Ph), 3.93–4.02 (m, 1H), 3.76–3.56 (m, 3H), 3.50

(d, 1H, J 14.4 Hz, H-1a), 3.39 (d, 1H, J 14.4 Hz, H-

1b), 3.27 (s, 3H, OCH₃); ¹³C NMR (50 MHz, CD₃OD):

d 140.3, 140.2, 139.8, 139.7 (4C-quat. Ph), 129.4–128.5

(20C, Ph), 101.2 (C-2), 85.0, 81.0, 79.8 (C-3, C-4, C-5),

76.4, 76.3, 75.9, 74.6 (4CH₂Ph), 74.2 (C-6), 70.0 (C-7),

52.3 (C-1), 48.1 (OCH₃); ESIMS: m/z calcd for

C₃₆H₃₉O₉S^ꢁ[M]^ꢁ: 647.23; found, 647.21.

SO₃CH₂CH₃); ¹³C NMR (125 MHz, CDCl₃):

d

138.4(2·), 138.1 (3C-quat. Ph), 128.4–127.6 (15C, Ph),

94.9 (C-2), 77.8, 77.3 (2 skeleton C), 74.9, 73.4

(2CH₂Ph), 72.3 (skeleton C), 72.0 (CH₂Ph), 69.0 (C-6),

67.9 (SO₃CH₂CH₂), 58.8 (C-1), 40.0 (C-3), 15.0

(SO₃CH₂CH₃);

MALDI-MS:

m/z

calcd

for

C₃₀H₃₆NaO₈S⁺[M+Na]⁺: 579.20; found, 579.65.

3.11. Ethyl 4,5,7-tri-O-benzyl-1,2,3-trideoxy-1-ethoxy-

sulfonyl-2-thio-a-^D-arabino-hept-2-ulopyranoside (12)

Compound 11 (3.14 g, 5.64 mmol) was converted by

method C to give 12 at ꢁ20 ꢁC for 1.5 h. The residue

was puriﬁed by column chromatography using

CH₂Cl₂–acetone (98:2) to aﬀord 12 as white crystals

(2.51 g, 74%): mp 75–76 ꢁC (EtOH); [a]_D+77.3 (c 0.4,

CHCl₃); R_f= 0.53 (CH₂Cl₂–acetone, 98:2); ¹H NMR

(200 MHz, CDCl₃): d 7.34–7.18 (m, 15H, Ph), 4.91 (d,

1H, J = 10.9 Hz, CH₂Ph), 4.67 (d, 1H, J = 11.9 Hz,

CH₂Ph), 4.62 (s, 1H, CH₂Ph), 4.56 (d, 1H,

3.9. Methyl 3,4,5,7-tetra-O-benzyl-1-deoxy-1-sodium-

sulfonato-b-^D-gluco-hept-2-ulopyranoside (9b)

Compound 2b (552 mg, 0.81 mmol) was converted by

method B to give compound 9b (523 mg, 96%): [a]_D

+46.1 (c 0.2, CHCl₃); R_f= 0.22 (CH₂Cl₂–MeOH,

G. Ma´jer et al. / Carbohydrate Research 342 (2007) 1393–1404

1401

J = 11.1 Hz, CH₂Ph), 4.55 (s, 1H, CH₂Ph), 4.49 (d, 1H,

J = 12.1 Hz, CH₂Ph), 4.29 (q, 2H, J = 7.1 Hz,

SO₃CH₂CH₃), 4,17–4.01 (m, 2H), 3.82–3.51 (m, 5H),

2.6–2.31 (m, 4H, SCH₂CH₃, H-2a, H- 2b), 1.29 (t, 3H,

J = 7.1 Hz, SCH₂CH₃), 1.20 (t, 3H, J = 7.5 Hz,

SO₃CH₂CH₃); ¹³C NMR (125 MHz, CDCl₃): d 138.3,

138.2 (2·) (3C-quat. Ph), 128.3–127.4 (15C, Ph), 84.5

(C-2), 77.9, 77.8 (2 skeleton C), 75.0 (CH₂Ph), 73.6 (skel-

eton C), 73.2, 71.8 (2CH₂Ph), 69.2 (C-6), 67.1

(SO₃CH₂CH₂), 60.1 (C-1), 38.1 (C-3), 21.3 (SCH₂CH₃),

15.1, 13.9 (SO₃CH₂CH₃, SCH₂CH₃); MALDI-MS: m/z

3.13. Ethyl 4,5,6,8-tetra-O-benzyl-2-deoxy-a-^D-gluco-oct-

3-ulopyranosonate (15)

A solution of diisopropylamine (504 lL, 3.60 mmol,

1.5 equiv) in dry THF (15 mL) was treated with 2.5 M

n-BuLi in hexane (1.44 mL, 3.60 mmol, 1.5 equiv) at

ꢁ15 ꢁC under argon atmosphere. After 15 min the solu-

tion was cooled to ꢁ60 ꢁC and dry ethyl acetate

(0.35 mL, 3.6 mmol, 1.5 mmol) was added. The mixture

was kept at ꢁ60 ꢁC for 15 min, then compound 14

(1.29 g, 2.4 mmol, 1.0 equiv) in THF was added. The mix-

ture was kept at ꢁ60 ꢁC for 30 min, then it was allowed to

warm up to room temperature, and concentrated. The

residue was diluted with CH₂Cl₂and was extracted with

water until neutral, then dried and evaporated. The crude

product was puriﬁed by column chromatography using

CH₂Cl₂–acetone (97:3) to aﬀord 15 (0.99 g, 66%): [a]_D

ꢁ6.6 (c 0.2, CHCl₃), lit.³⁶[a]_Dꢁ5.3; R_f= 0.6 (CH₂Cl₂–

calcd for C₃₂H₄₀NaO₇S₂[M+Na]⁺: 623.21; found,

þ

623.34.

3.12. Methyl 4,5,7-tri-O-benzyl-1,3-dideoxy-1-ethoxy-

sulfonyl-a-^D-arabino-hept-2-ulopyranoside (13a) and

methyl 4,5,7-tri-O-benzyl-1,3-dideoxy-1-ethoxysulfonyl-

b-^D-arabino-hept-2-ulopyranoside (13b)

1

acetone, 95:5); The H and ¹³C NMR data were consis-

Thioglycoside donor 12 (300 mg, 0.50 mmol) was con-

verted by method A to give a mixture of 13a and

13b. The anomers were separated by column chroma-

tography using CH₂Cl₂–acetone (60:1). Compound

13a was isolated as a syrup (162 mg, 57%): [a]_D+30.0

(c 0.2, CHCl₃); R_f= 0.26 (n-hexane–EtOAc, 7:3); ¹H

NMR (200 MHz, CDCl₃): d 7.32–7.17 (m, 15H, Ph),

4.90 (d, 1H, J = 10.8 Hz), 4.69 (d, 1H, J = 11.4 Hz,

CH₂Ph), 4.61–4.47 (m, 4H, CH₂Ph), 4.30 (q, 2H,

J = 7.1 Hz, SO₃CH₂CH₃), 4.07–3.95 (ddd, 1H, H-5),

3.78–3.50 (m, 5H), 3.36 (d, 1H, J = 15.0 Hz, H-1a),

3.27 (s, 3H, OCH₃), 2.81 (dd, 1H, J = 5.0, 13.2 Hz,

H-3_eq), 1.84 (dd, 1H, J = 11.2, 13.2 Hz, H-3_ax), 1.36

(t, 3H, J = 7.1 Hz, SO₃CH₂CH₃); ¹³C NMR (50 MHz,

CDCl₃): d 138.4, 138.3, 138.1 (3C-quat. Ph), 128.3–

127.5 (15C, Ph), 97.8 (C-2), 77.6, 77.4 (2 skeleton C),

74.9, 73.3 (2CH₂Ph), 72.4 (skeleton C), 71.7 (CH₂Ph),

68.9, 66.9 (SO₃CH₂CH₃, C-7) 54.6 (C-1), 48.4

(OCH₃), 38.4 (C-3), 15.1 (SO₃CH₂CH₃). Anal. Calcd

for C₃₁H₃₈O₈S: C, 65.24; H, 6.71. Found: C, 65.17;

H, 6.78. Compound 13b was isolated as a syrup

(58 mg, 20%): [a]_D+18.8 (c 0.2, CHCl₃); R_f= 0.31 (n-

hexane-EtOAc, 7:3); ¹H NMR (200 MHz, CDCl₃): d

7.39–7.19 (m, 15H, Ph), 4.93 (d, 1H, J = 10.9 Hz,

CH₂Ph), 4.77 (d, 1H, J = 11.6 Hz, CH₂Ph), 4.66–4.53

(m, 4H, CH₂Ph), 4.35 (q, 2H, J = 7.1 Hz,

SO₃CH₂CH₃), 3.94–3.83 (m, 1H, H-5), 3.78–3.55 (m,

5H), 3.48 (d, 1H, J = 14.6 Hz), 3.47 (s, 3H, OCH₃),

2.80 (dd, 1H, J = 4.7, 13.5 Hz, H-3_eq), 2.03 (dd, 1H,

J = 10.6, 13.5 Hz, H-3_ax), 1.43 (t, 3H, J = 7.1 Hz,

SO₃CH₂CH₃); ¹³C NMR (50 MHz, CDCl₃): d 138.2,

138.1 (2·) (3C-quat. Ph), 128.3–127.5 (15C, Ph), 98.1

(C-2), 77.5, 77.2, 74.9 (C-4, C-5, C-6), 74.6, 73.3, 71.2

(3CH₂Ph), 69.3, 67.2 (SO₃CH₂CH₃, C-7), 53.3 (C-1),

49.1 (OCH₃), 34.1 (C-3), 15.0 (SO₃CH₂CH₃). Anal.

Calcd for C₃₁H₃₈O₈S: C, 65.24; H, 6.71. Found: C,

65.32; H, 6.63.

tent with those reported previously.³⁷Anal. Calcd for

C₃₈H₄₂O₈: C, 72.82; H, 6.75. Found: C, 72.79; H, 6.73.

3.14. Ethyl (ethyl 4,5,6,8-tetra-O-benzyl-2,3-dideoxy-3-

thio-a-^D-gluco-oct-3-ulopyranosid)onate (16)

Compound 15 (740 mg, 1.18 mmol) was converted by

method C at 0 ꢁC for overnight to give 16. Puriﬁcation

by column chromatography using CH₂Cl₂–acetone

(98:2) aﬀorded compound 16 (497 mg, 63%): [a]_D

1

+84.0 (c 0.2, CHCl₃); R_f= 0.62. H NMR (500 MHz,

CDCl₃): d 7.21–7.34 (m, 20H, Ph), 5.00 (d, 1H,

J = 11.7 Hz, CH₂Ph), 4.90 (d, 1H, J = 11.7 Hz, CH₂Ph),

4.88–4.84 (m, 3H, CH₂Ph), 4.61 (d, 1H, J = 11.0 Hz,

CH₂Ph), 4.59 (d, 1H, J = 12.1 Hz, CH₂Ph), 4.50 (d,

1H, J = 12.1 Hz, CH₂Ph), 4.37 (d, 1H, J = 9.4 Hz),

4.19 (t, 1H, J = 9.2 Hz), 3.98–4.05 (m, 3H), 3.75 (dd,

2H, J= 11.3, 4.6 Hz, H-6a), 3.68 (dd, 1H, J = 11.4,

1.7 Hz, H-6b), 3.63 (t, 1H, J = 9.6 Hz), 3.00 (d, 1H,

J_2a,2b= 14.5 Hz, H-2a), 2.96 (d, 1H, H-2b), 2.41–2.55

(m, 2H, SCH₂CH₃), 1.23 (t, 3H, J = 7.5 Hz, SCH₂CH₃),

1.18 (d, 3H, J = 7.1 Hz, COOCH₂CH₃); ¹³C NMR

(125 MHz, CDCl₃): d 169.0 (COOEt), 138.6 (2·),

138.5, 138.2 (4C-quat. Ph), 128.4–127.3 (20C, Ph), 89.7

(C-3), 83.9, 80.7, 78.2 (C-4, C-5, C-6), 75.5, 75.2, 75.0

(3CH₂Ph), 73.7 (C-7), 73.2 (CH₂Ph), 68.8 (C-8), 60.5

(COOCH₂CH₃), 42.8 (C-2), 19.8 (SCH₂CH₃), 14.2,

14.0 (COOCH₂CH₃, SCH₂CH₃). Anal. Calcd for

C₄₀H₄₆O₇S: C, 71.61; H, 6.91. Found: C, 71.70; H, 6.82.

3.15. Ethyl (methyl 4,5,6,8-tetra-O-benzyl-2-deoxy-a-^D-

gluco-oct-3-ulopyranosid)onate (17a) and ethyl (methyl

4,5,6,8-tetra-O-benzyl-2-deoxy-b-^D-gluco-oct-3-ulopyr-

anosid)onate (17b)

Compound 16 (335 mg, 0.50 mmol) was converted by

method A to give a mixture of 17a and 17b. The anomers

1402

G. Ma´jer et al. / Carbohydrate Research 342 (2007) 1393–1404

were separated by column chromatography using

EtOAc–n-hexane (8:2). Compound 17a was isolated as

a syrup (70 mg, 22%): [a]_D+38.3 (c 0.3, CHCl₃), lit.²⁴

+35.8; R_f= 0.250 (n-hexane–EtOAc, 8:2); ¹H NMR

(500 MHz, CDCl₃): d 7.33–7.19 (m, 20H, Ph), 4.98 (d,

1H, J = 11.1 Hz, CH₂Ph), 4.91 (d, 1H, J = 11.6 Hz,

CH₂Ph), 4.89 (d, 1H, J = 11.6 Hz, CH₂Ph), 4.85 (d,

1H, J = 10.6 Hz, CH₂Ph), 4.83 (d, 1H, J = 11.00 Hz,

CH₂Ph), 4.62 (d, 1H, J = 5.3 Hz, CH₂Ph), 4.59 (d, 1H,

J = 4.0 Hz, CH₂Ph), 4.52 (d, 1H, J = 12.1 Hz, CH₂Ph),

4.12 (t, 1H, J = 8.9 Hz), 4.04–4.00 (m, 3H), 3.75 (dd,

1H, J = 11.2, 3.7 Hz, H-8a), 3.70–3.67 (m, 3H), 3.29

(s, 3H, OCH₃), 2.82 (d, 1H, J = 14.0 Hz, H-2a), 2.78

(d, 1H, J = 14.0 Hz, H-2b), 1.17 (t, 3H, J = 7.13 Hz,

COOCH₂CH₃); ¹³C NMR (125 MHz, CDCl₃): d 169.0

(COO), 138.6, 138.4, 138.3, 138.1 (4C-quat. Ph),

128.3–127.4 (20C, Ph), 100.1 (C-3), 83.3, 80.8, 78.3 (C-

4, C-5, C-6), 75.5, 75.4, 75.0, 73.3 (4CH₂Ph), 72.6 (C-

7), 68.6 (C-8), 60.5 (COOCH₂CH₃), 47.9 (OCH₃), 36.9

(C-2), 14.0 (COOCH₂CH₃). Anal. Calcd for C₃₉H₄₄O₈:

C, 73.10; H, 6.90. Found: C, 72.98; H, 6.89. Compound

17b (100 mg, 31%): [a]_D+41.7 (c 0.2, CHCl₃), lit.²⁴

ꢁ28.5; R_f= 0.30 (n-hexane–EtOAc, 8:2); ¹H NMR

(500 MHz, CDCl₃): d 7.19–7.32 (m, 20H, Ph), 4.86 (d,

1H, J = 11.2 Hz, CH₂Ph), 4.84 (d, 1H, J = 1.5 Hz,

CH₂Ph), 4.81 (d, 1H, J = 1.8 Hz, CH₂Ph), 4.77 (d, 1H,

J = 11.2 Hz, CH₂Ph), 4.64–4.60 (m, 3H, CH₂Ph), 4.52

(d, 1H, J = 12.1 Hz, CH₂Ph), 4.13–4.03 (m, 2H,

COOCH₂CH₃), 3.89 (dd, 1H, J = 10.2, 8.8 Hz), 3.83–

3.78 (m, 3H), 3.73 (dd, 1H, J = 8.4, 7.4 Hz, 8-Ha), 3.70

(dd, 1H, J = 10.8, 1.7 Hz, H-8b), 3.43 (s, 3H, OCH₃),

2.96 (d, 1H, J = 14.0 Hz, H-2a), 2.81 (d, 1H,

J = 14.0 Hz, H-2b), 1.20 (t, 3H, J = 7.16 Hz,

COOCH₂CH₃); ¹³C NMR (125 MHz, CDCl₃): d 169.0

(COOEt), 138.4, 138.3, 138.1, 138.1 (4C-quat. Ph),

128.3–127.4 (20C, Ph), 101.6 (C-3), 83.4, 79.6, 77.5 (C-

4, C-5, C-6), 74.9, 74.7, 73.5 (3CH₂Ph), 73.4 (C-7), 73.3

(CH₂Ph) 68.8 (C-8), 60.4 (COOCH₂CH₃), 48.9 (OCH₃),

37.0 (C-2), 14.1 (COOCH₂CH₃). Anal. Calcd for

C₃₉H₄₄O₉: C, 73.10; H, 6.92. Found: C, 73.19; H, 6.83.

CHCl₃); lit.³¹+24.7; R_f= 0.55 (CH₂Cl₂–acetone 95:5);

1

The H and ¹³C NMR data were consistent with those

reported previously.^31,38Anal. Calcd for C₃₅H₃₈O₆: C,

75.79; H, 6.91. Found: C, 75.69; H, 6.93.

3.17. Ethyl 3,4,5,7-tetra-O-benzyl-1,2-dideoxy-2-thio-a-

D-gluco-hept-2-ulopyranoside (19)

Compound 18 (555 mg, 1.00 mmol) was converted by

method C at 0 ꢁC for 3.5 h to give 19, and puriﬁed by col-

umn chromatography using CH₂Cl₂–acetone (98:2).

Compound 19 (180 mg, 30%): [a]_D+65.0 (c 0.2, CHCl₃);

R_f= 0.80 (CH₂Cl₂–acetone, 120:2); ¹H NMR (200 MHz,

CD₃Cl₃): d 7.37–7.14 (m, 20H, Ph), 4.91 (d, 1H,

J = 11.6 Hz, CH₂Ph), 4.85 (s, 2H, CH₂Ph), 4.83 (d, 1H,

J = 11.6 Hz, CH₂Ph), 4.74 (d, 1H, J = 11.6 Hz, CH₂Ph),

4.64 (d, 1H, J = 11.6 Hz, CH₂Ph), 4.61 (d, 1H,

J = 11.6 Hz, CH₂Ph), 4.54 (d, 1H, J = 11.4 Hz, CH₂Ph),

4.47 (d, 1H, J = 11.6 Hz, CH₂Ph), 4.12–4.06 (m, 2H),

3.73 (dd, 1H, J = 4.4, 11.1 Hz) 3.76–3.59 (m, 2H), 3.41

(d, 1H, J = 9.2 Hz, H-3), 2.58–2.40 (m, 2H, SCH₂CH₃),

1.61 (s, 3H, CH₃-1), 1.23 (t, 3H, J = 7.5 Hz, SCH₂CH₃);

¹³C NMR (50 MHz, CD₃Cl₃): d 138.8, 138.2 (3·) (4C-

quat. Ph), 128.8–127.5 (20C, Ph), 89.1 (C-2), 85.8, 83.9,

78.5 (C-3, C-4, C-5), 75.6, 75.6, 74.9, 73.3 (4CH₂Ph),

72.9 (C-6), 68.9 (C-7), 27.5 (C-1), 19.8 (SCH₂CH₃),

14.4 (SCH₂CH₃). Anal. Calcd for C₃₇H₄₂O₅S: C, 74.22;

H, 7.07. Found: C, 74.15; H, 7.14.

3.18. Methyl 3,4,5,7-tetra-O-benzyl-1-deoxy-a-^D-gluco-

hept-2-ulopyranoside (20a) and methyl 3,4,5,7-tetra-O-

benzyl-1-deoxy-b-^D-gluco-hept-2-ulopyranoside (20b)

Compound 19 (317 mg, 0.53 mmol) was converted by

method A to give a mixture of 20a and 20b. The ano-

mers were separated by column chromatography using

CH₂Cl₂–acetone (60:1). Compound 20a was isolated as

a syrup (55 mg, 18%): [a]_D+20.3 (c 0.4, CHCl₃), lit.³¹

+21.3; R_f= 0.59 (n-hexane–EtOAc 7:3); ¹H NMR: d

7.41–7.10 (20H, Ph) 4.93 (d, 1H, J = 11.0 Hz, CH₂Ph),

4.91 (d, 1H, J = 11.3 Hz, CH₂Ph), 4.87 (d, 1H,

J = 11.1 Hz, CH₂Ph), 4.83 (d, 1H, J = 10.8 Hz, CH₂Ph),

4.68 (d, 1H, J = 12.3 Hz, CH₂Ph), 4.63 (d, 1H,

J = 13.2 Hz, CH₂Ph), 4.52 (d, 1H, J = 10.82 Hz,

CH₂Ph), 4.54 (s, 1H, CH₂Ph), 4.13–4.03 (m, 1H),

3.74–3.62 (m, 4H), 3.35 (d, 2H, J = 9.6 Hz, H-3), 3.22

(s, 3H, OCH₃), 1.27 (s, 3H, CH₃-1); ¹³C NMR

(125 MHz, CDCl₃): d 138.7, 138.2, 138.2, 138.0 (4C-

quat. Ph), 128.7–127.5 (20C, Ph), 100.3 (C-2), 83.8,

83.3, 78.6 (C-3, C-4, C-5), 75.6, 75.5, 74.9, 73.3

(4CH₂Ph), 71.5 (C-6 or C-7), 68.8 (C-6 or C-7), 47.9

(OCH₃), 19.9 (C-1). Anal. Calcd for C₃₆H₄₀O₆: C,

76.03; H, 7.09. Found: C, 76.11; H, 7.01. Compound

20b (75 mg, 25%): [a]_D+9.5 (c 0.1, CHCl₃); R_f= 0.69

3.16. 3,4,5,7-Tetra-O-benzyl-1-deoxy-a-^D-gluco-hept-2-

ulopyranose (18)

To a stirred solution of compound 14 (2.70 g, 5.0 mmol)

in dry Et₂O (30 mL) was added freshly prepared

CH₃MgI in dry Et₂O (25 mL, CH₃MgI content

ꢀ1.10 g, 6.50 mmol) at ꢁ10 ꢁC. The mixture was kept

at ꢁ10 ꢁC until the TLC showed complete conversion

(15 min). The reaction was quenched by addition of

5% aqueous NH₄Cl, the mixture was diluted with

CH₂Cl₂, extracted three times with water, dried and

evaporated. The residue was puriﬁed by column chro-

matography using CH₂Cl₂–acetone (95:5) to give 18 as

white crystals (1.26 g, 84%): mp 83–84 ꢁC (ethyl-ace-

tate–n-hexane), lit.³¹92–93 ꢁC; [a]_D+23.9 (c 0.3,

1

(n-hexane-EtOAc, 7:3); H NMR (500 MHz, CDCl₃): d

7.35–7.14 (m, 20H, Ph), 4.91 (d, 1H, J = 11.3 Hz,

G. Ma´jer et al. / Carbohydrate Research 342 (2007) 1393–1404

1403

CH₂Ph), 4.87 (d, 1H, J = 11.1 Hz, CH₂Ph), 4.83 (d, 1H,

References

J = 10.8 Hz, CH₂Ph), 4.69 (d, 1H, J = 11.3 Hz, CH₂Ph),

4.61 (d, 1H, J = 12.2 Hz, CH₂Ph), 4.53 (d, 1H,

J = 10.8 Hz, CH₂Ph), 4.52 (d, 1H, J = 12.2 Hz, CH₂Ph),

4.11–4.04 (m, 1H, H-6), 3.71 (dd, 1H, J = 2.8, 10.4 Hz),

3.67–3.63 (m, 3H), 3.35 (d, 1H, J = 9.6 Hz, H-3), 3.22 (s,

3H, OCH₃), 1.27 (s, 3H, CH₃-1); ¹³C NMR (125 MHz,

CDCl₃): d 138.7 (2·), 138.4, 138.2 (4C-quat. Ph),

128.3–127.1 (20C, Ph), 102.0 (C-2), 84.0, 82.6, 78.2 (C-

3, C-4, C-5), 75.5, 75.0, 74.1, 73.4 (4CH₂Ph), 71.7 (C-

6), 69.4 (C-7), 48.6 (OCH₃), 16.7 (C-1). Anal. Calcd for

C₃₆H₄₀O₆: C, 76.03; H, 7.09. Found: C, 76.16; H, 6.96.

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2. Thomas, W. A. Prog. Nucl. Magn. Reson. Spectrosc. 1997,

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448–457.

4. Tvarosˇka, I.; Taravel, F. R. Adv. Carbohydr. Chem.

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8644.

3.19. Azido 3,4,5,7-tetra-O-benzyl-1,2-dideoxy-1-ethoxy-

sulfonyl-a-^D-gluco-hept-2-ulopyranoside (22)

8. van Beuzekom, A. A.; de Leeuw, F. A. A. M.; Altona, C.

Magn. Reson. Chem. 1990, 28, 68–74.

To a solution of 21²³(800 mg 1.21 mmol) in dry CH₂Cl₂

(8 mL) Me₃SiN₃(191 lL, 1.45 mmol, 1.2 equiv) and

BF₃ÆEt₂O (304 lL, 2.42 mmol, 2.00 equiv) were added,

and the mixture was stirred at rt for 3 h. The residue

was diluted with CH₂Cl₂and was extracted with water

until neutral, then dried and evaporated. The residue

was puriﬁed by column chromatography using

CH₂Cl₂–acetone (97:3) to aﬀord 22 (680 mg, 78%):

[a]_D+67.1 (c 0.5); R_f= 0.41 (CH₂Cl₂–acetone, 97:3);

¹H NMR (200 MHz, CDCl₃): d 7.39–7.14 (m, 20H,

Ph), 5.03 (d, 1H, J 11.2 Hz, CH₂Ph), 4.98–4.73 (m,

4H, CH₂Ph), 4.64–4.47 (m, 3H, CH₂Ph), 4.30–4.12 (m,

3 H), 4.09–3.71 (m, 5H), 3.70 (d, 1H, J = 14.0 Hz, H-

1a), 3.52 (d, 1H, J = 14.0 Hz, H-1b), 1.26 (t, 3H,

J = 7.1 Hz, SO₃OCH₂CH₃); ¹³C NMR (50 MHz,

CDCl₃): d 138.0, 137.8, 137.6 (2·) (4C-quat. Ph),

128.5–127.6 (20C, Ph), 91.4 (C-2), 83.3, 80.1, 77.3 (C-

3, C-4, C-5), 75.7, 75.4, 75.1, 73.4 (4CH₂Ph), 74.6 (C-

6), 68.2, 68.1 (SO₃CH₂CH₃, C-7), 53.5 (C-1), 151

(SO₃CH₂CH₃); IR (KBr): 3050, 2880, 2130 (N₃), 1510,

1460, 1360, 1100, 920, 740, 700 cm^ꢁ1; MALDI-MS:

m/z calcd for C₃₇H₄₁N₃NaO₈S⁺[M+Na]⁺: 710.25;

found, 710.16.

9. San Fabian, J.; Guilleme, J.; Diez, E. J. Mol. Struct. 1998,

426, 117–133.

10. Thibaudeau, C.; Stenutz, R.; Hertz, B.; Klepach, T.; Zhao,

S.; Wu, Q. Q.; Carmichael, I.; Serianni, A. S. J. Am. Chem.

Soc. 2004, 126, 15668–15685.

´

11. (a) Parella, T.; Sanchez-Ferrado, F.; Virgili, A. Magn.

´

Reson. Chem. 1994, 32, 657–664; (b) Parella, T.; Sanchez-

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Article Doi

Synthesis of ketopyranosyl glycosides and determination of their anomeric configuration on the basis of the three-bond carbon-proton couplings

DOI: 10.1016/j.carres.2007.05.006

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