A Novel approach to β-(1-→4)-linked thiodisaccharides starting from disulfide sugars

Article abstract of DOI:10.1007/PL00010292

Glycosylation of monosaccharides 4, 8, and 10 containing an intramolecular disulfide bridge by applying Helferich-conditions and an excess of acctobromohexose 5 or 11 as donor substrate yielded 6-thiocyanato-β-(1-→4)-thiodisaccharides 6, 9, and 12 regio-and stereospecifically in moderate to good yields. In addition, the formation of trisaccharides 7 and 13 could be observed, albeit in low yield. This novel route for thioglycoside formation may open access to a variety of bioactive disaccharide analogues.

Full text of DOI:10.1007/PL00010292

Monatshefte fuÈr Chemie 130, 1137±1145 (1999)
A Novel Approach to b-(1!4)-Linked
Thiodisaccharides Starting from Disul®de
Sugars
1
1
2
È
Irmgard Wenzl , Hanspeter Kahlig , Frank M. Unger ,
and Walther Schmid1;Ã
1
È
Institut fuÈr Organische Chemie der Universitat Wien, A-1090 Wien, Austria
È
È
Institut fuÈr Chemie der Universitat fur Bodenkultur, A-1190 Wien, Austria
2
Summary. Glycosylation of monosaccharides 4, 8, and 10 containing an intramolecular disul®de
bridge by applying Helferich-conditions and an excess of acetobromohexose 5 or 11 as donor
substrate yielded 6-thiocyanato-ꢀ-(1!4)-thiodisaccharides 6, 9, and 12 regio- and stereospeci®cally
in moderate to good yields. In addition, the formation of trisaccharides 7 and 13 could be observed,
albeit in low yield. This novel route for thioglycoside formation may open access to a variety of
bioactive disaccharide analogues.
Keywords. Disul®de sugars; Thiodisaccharides; Thioglycosides; Helferich glycosylation.
Ein neuer Zugang zu b-(1!4)-verknuÈpften Thiodisacchariden ausgehend von Disul®dzuckern
Zusammenfassung. Die Glykosidierung der Monosaccharide 4, 8 und 10, welche eine
intramolekulare Disul®dbruÈcke besitzen, liefert unter Anwendung von Helferich-Bedingungen und
È
einem Uberschuû entsprechender Acetobromohexose 5 oder 11 als Donor regio- und stereospezi®sch
È
die 6-Thiocyanato-ꢀ-(1!4)-thiodisaccharide 6, 9 und 12 in guten Ausbeuten. Zusatzlich wurde,
wenn auch in geringer Ausbeute, die Bildung der Trisaccharide 7 und 13 beobachtet. Dieser neue
È
Syntheseweg zur Darstellung von thioglykosidischen VerknuÈpfungen offnet einen Zugang zu einer
Vielzahl an bioaktiven Disaccharid-Analoga.
Introduction
The increasing interest in thioglycosides is due to their utility as glycosyl donors in
modern glycosylation reactions [1]. Furthermore, their potential as analogues of
naturally occurring, biologically active saccharides has obtained great attention [2].
Since thioglycosidic linkages are hydrolytically stabilized towards the action of
various glycosidases [3], they have been frequently used for structure-activity
relationship studies involving carbohydrate-enzyme interactions [4]. However, a
general application of thioglycosides as analogues of receptor-active saccharidic
ligands is not always feasible [5].
Ã
Corresponding author

1138
I. Wenzl et al.
The formation of the thioglycosidic bond is usually achieved via two general
strategies: (a) base-promoted S-glycosylation or anomeric S-alkylation [6], or (b)
Lewis acid catalyzed S-glycosylation [7]. Additionally, methods applying the
Michael addition of 1-thio sugars to levoglucosenon [8], or the nucleophilic
opening of cyclic sulfate carbohydrates with 1-thio sugars have been described [9].
Here we report on the formation of thioglycosidic linkages starting from
disul®de sugars. These carbohydrates are of particular interest because of their
potential use in biological redox reactions [10] and their change in hydrophobicity
compared to their natural analogues, thus making them a challenging object for
lectin-binding studies [11].
Results and Discussion
We started our studies with the allyl 4,6-epidithio-N-acetyl-galactosamin analogue
4, which was easily prepared following essentially the procedure of Hill et al. [12].
Thus, starting from allyl 2-acetamido-2-deoxy-3-O-benzoyl-ꢁ-D-glucopyranoside
1 [13], the 4,6-dimesyl derivative 2 was prepared by treatment with an excess of
methansulfonyl chloride in pyridine (Scheme 1). Displacement of the mesylate
groups by thiocyanate functionalities yielded the galacto-con®gured compound 3
which was transformed to the 4,6-epidithio analogue 4 by applying the Zemplen
saponi®cation procedure. This conversion of dithiocyanate to the disul®de sugar is
initiated by a nucleophilic attack of an alkoxide anion to the carbon atom of the
thiocyanate-group, generating a reactive thiolate anion which subsequently forms
the disul®de bond in an intramolecular reaction [14]. Thus, compound 4 could be
obtained in moderate to good yield.
Treatment of 4 with a mixture of Hg(CN)2 and HgBr2 [15, 16] followed by
addition of an excess of acetobromogalactose 5 [17] yielded the thiodisaccharide 6
(Scheme 2) in 50% yield. Additionally, the formation of the trisaccharide 7 could
be observed in low yields. The predominant S-glycosylation may be explained by
cyanide opening of the disul®de bond [18], generating a soft thiolate nucleophile
Scheme 1

ꢀ-(1!4)-Linked Thiodisaccharides
1139
Scheme 2
which subsequently substitutes the bromide at the anomeric center of the galactose
derivative 5. Since the substitution obviously follows an SN2 mechanism, the
thioglycosidic linkage is formed in a diastereospeci®c manner yielding the ꢀ-
connectivity exclusively.
The stereochemistry of the thioglycosidic linkage could be assigned easily by
0
0
NMR analysis. Thus, the J1 ,2 coupling constants in the thio-linked galactose
moiety of disaccharide 6 were 9.96 and 10.60 Hz in the trisaccharide derivative 7, a
magnitude consistent with the ꢀ-glycosidic linkage. The presence of the C-10ꢀGal†
-
S-C-4ꢀGalNAc† linkage could be con®rmed by a typical high-®eld shift of the protons
and carbons involved.
To further demonstrate the applicability of this method we chose methyl 2,3-di-
O-acetyl-4,6-dideoxy-4,6-epidithio-ꢁ-D-galactopyranoside 8 (Scheme 3) as accep-
tor substrate. Following the glycosylation protocol described we could obtain the
thiodisaccharide 10 in 68% yield. Again, the ꢀ-(1!4) linkage was formed
exclusively as judged by extensive NMR analysis.
Applying the glycosylation procedure to the unprotected acceptor analogue 10
and utilizing the acetobromoglucose derivative 11 as donor yielded the ꢀ-(1!4)
linked thiodisaccharide 12 in 19% yield (Scheme 4). In analogy to compound 4 the
additional glycosylation of a hydroxyl group took place yielding the trisaccharide
13. To facilitate the structural assignment, we transformed the trisaccharide 13 to
its peracetylated derivative 14.
1
Consequently, extensive NMR studies allowed complete assignment of the H
and 13C signals and con®rmed the C-100
-O-C-2ꢀGal† connectivity of 14. In fact,
ꢀGlc†
the HMBC spectrum exhibited a cross peak between C-100
and H-2ꢀGal†
,
ꢀGlc†
con®rming the type of the (1!2) linkage. The stereochemistry was easily
00 00
established by analysis of the coupling constants showing J1 ,2 ˆ 7.9 Hz in the
glucose residue, typical for a ꢀ-connectivity. All 1H and 13C signals of the relevant
di- and trisaccharides (6, 7, 9, and 14) were assigned by 2D experiments.

1140
I. Wenzl et al.
Scheme 3
Scheme 4
In conclusion, we were able to demonstrate a novel approach towards the
synthesis of various thiodisaccharides. The applicability of well-known glycosyla-
tion procedures to sugars containing an intramolecular disul®de bridge opens a new
synthetic route for generating thioglycosidic linkages. In addition, the thiocyanato
functionality formed in the course of the reaction may be utilized for further
transformations on the products formed.
Experimental
Starting materials were obtained from commercial suppliers and were generally used without further
1
puri®cation. Melting points were determined on a Ko¯er apparatus and are uncorrected. H and

ꢀ-(1!4)-Linked Thiodisaccharides
1141
13C NMR (J modulated) spectra were recorded in CDCl3 unless otherwise given, using CHCl3 as
internal standard, on a Bruker DRX 400 NMR spectrometer at 400.13 and 100.61 MHz or on a
Bruker DPX 250 NMR spectrometer at 250.13 and 62.90 MHz. Chemical shifts (ꢂ) are given in ppm
and coupling constants (J) in Hz. IR spectra were run on a Perkin Elmer 1600 FT-IR spectrometer.
Optical rotations were measured on a Perkin Elmer 341 polarimeter in a 1 dm cell. TLC was
performed on precoated Merck plates (silica gel 60 F254). Detection was performed using UV light,
I2, and by dipping the plates into a solution of 2% Ce(SO4)2 Á 4H2O in 5.5% H2SO4 with subsequent
heating. Flash chromatography was performed with Merck silica gel 60 (230±400 mesh). All
reactions were carried out under argon. Elemental analysis agreed with the calculated values.
Allyl 2-acetamido-3-O-benzoyl-2-deoxy-4,6-di-O-methanesulfonyl-ꢁ-D-glucopyranoside
(2; C20H27NO11S2)
To a solution of 5.06 g 1 (13.85 mmol) and a catalytic amount of 4-dimethylaminopyridine (DMAP)
in 70 cm3 pyridine at 0ꢁC, 4.3 cm3 methanesulfonyl chloride (55.55 mmol) were added dropwise.
After 2 h the temperature was raised to room temperature, and the solution was stirred for further
14 h. The solvent was removed by coevaporation with toluene. The residue was treated with 100 cm3
saturated aqueous NaHCO3 solution and extracted three times with 100 cm3 dichloromethane. The
organic layer was separated, dried over MgSO4, ®ltered, and the solvent was evaporated in vacuo.
Flash chromatography (ethyl acetate/hexane, 2:1) of the residue afforded 6.03 g 2 (83%) as a
colorless foam.
TLC (hexane/ethyl acetate, 1:2): Rf ˆ 0.25; [ꢁ]2D0 ˆ ‡63.27 (c ˆ 1.10, CHCl3); IR: ꢃ ˆ 3294.8,
1
3033.2, 2938.2, 1725.1, 1665.9, 1537.5 cmꢂ1; H NMR (250 MHz): ꢂ ˆ 8.03±7.40 (m, 5H, C6H5),
5.88 (m, 1H, H20), 5.79 (d, 1H, JNH,2 ˆ 9.60, NHAc); 5.58 (dd, 1H, J2,3 ˆ 10.97, J3,4 ˆ 9.37, H3),
5.30 (m, 2H, H30), 4.94 (m, 2H, J1,2 ˆ 3.66, H1, H4), 4.46 (m, 3H, J6a,5 ˆ 4.34, J6b,5 ˆ 2.05,
J6a,6b ˆ 11.19, H2, H6a, H6b), 4.27 (m, 1H, H10), 4.15 (ddd, 1H, H5), 4.04 (m, 1H, H10), 3.08 (s, 3H,
SO2CH3), 2.85 (s, 3H, SO2CH3), 1.82 (s, 3H, NHCOCH3) ppm; 13C NMR (62.9 MHz): ꢂ ˆ 169.85,
166.64, 133.81, 132.70, 129.98, 128.79, 128.66, 118.88, 96.32, 74.32, 70.95, 69.12, 67.77,
66.85, 52.02, 38.80, 37.71, 22.98 ppm; MS (FI, 7 kV, 3 mA, 135ꢁC): m/z (rel. intensity) ˆ 522.5
(100), 486.5 (94).
Allyl 2-acetamido-3-O-benzoyl-2,4,6-trideoxy-4,6-dithiocyanato-ꢁ-D-galactopyranoside
(3; C20H21N3O4S2)
A suspension of 3.3 g dimesylate 2 (6.33 mmol) and 6.6 g KSCN (67.91 mmol) in 40 cm3 DMF was
stirred at 120ꢁC for 72 h. The solvent was removed under vacuum, and the residue was puri®ed by
¯ash chromatography. The product 3 was obtained as a colorless foam (1.34 g, 47%).
TLC (ethyl acetate/hexane, 4:1): Rf ˆ 0.77; [ꢁ]2D0 ˆ ‡33.78 (c ˆ 1.19, CHCl3); IR: ꢃ ˆ 3306.3,
1
2941.5, 2158.7, 1724.6, 1666.4, 1537.7 cmꢂ1; H NMR (400 MHz) ꢂ ˆ 8.08±7.45 (m, 5H, C6H5),
5.89 (m, 1H, H20), 5.77 (d, 1H, JNH,2 ˆ 9.35, NHAc); 5.56 (dd, 1H, J2,3 ˆ 11.32, J3,4 ˆ 3.94, H3),
5.33 (m, 2 H, H30), 4.97 (d, 1H, J1,2 ˆ 3.94, H1), 4.71 (ddd, 1H, H2), 4.60 (ddd, 1H, J4.5 ˆ 1.48,
J5,6b ˆ 3.94, J5,6a ˆ 8.86, H5), 4.33 (m, 1H, H10), 4.25 (dd, 1H, H4), 4.09 (m, 1H, H10), 3.28 (ddd,
2H, J6a,6b ˆ 13.78, H6a, H6b), 1.89 (s, 3H, NHCOCH3) ppm; 13C NMR (100 MHz): ꢂ ˆ 170.01,
166.31, 134.01, 132.32, 130.20, 128.66, 128.21, 119.56, 110.92, 110.57, 96.65, 69.69, 69.30,
68.05, 55.58, 48.06, 35.72, 23.16 ppm; MS (FI, 7 kV, 3 mA, 140ꢁC): m/z (rel. intensity) 448.3 (18),
395.2 (100).
Allyl 2-acetamido-2,4,6-trideoxy-4,6-epidithio-ꢁ-D-galactopyranoside (4; C11H17NO4S2)
Dithiocyanate 3 (0.557 g, 1.24 mmol) was dissolved in 16 cm3 methanol. After addition of 9.0 cm3
0.1 M sodium methoxide in methanol, the solution was re¯uxed for 10 min and was further stirred for

1142
I. Wenzl et al.
‡
1 h at room temperature. The reaction mixture was neutralized with Dowex 50 W (H ), ®ltered, and
evaporated in vacuo to dryness. Column chromatography gave 0.118 g 4 (31%) as yellow crystals.
TLC (ethyl acetate/hexane, 4:1): Rf ˆ 0.32; m.p.: 195ꢁC (decomposition); [ꢁ]D20 ˆ ‡202.58
(c ˆ 1.24, CH3OH); IR: ꢃ ˆ 3294.3, 1648.2, 1549.4 cm ꢂ1
;
1H NMR (250 MHz, D2O/CD3OD):
ꢂ ˆ 5.94 (m, 1H, H20), 5.26 (m, 2H, H30), 4.88 (d, 1H, J1,2 ˆ 3.34, H1), 4.85 (m, 1H, H5), 4.45 (dd,
1H, J2,3 ˆ 10.96, J3,4 ˆ 4.79, H3), 4.35 (dd, 1H, H2), 4.22 (m, 1H, H10), 4.10 (dd, 1H, J4.5 ˆ 2.74,
H4), 4.02 (m, 1H, H10), 3.43 (dd, 1H, J6a,5 ˆ 4.57, J6a,6b ˆ 11.88, H6a), 3.24 (dd, 1H, J6b,5 ˆ 1.37,
H6b), 1.99 (s, 3H, NHCOCH3) ppm; 13C NMR (62.9 MHz, D2O/CD3OD): ꢂ ˆ 135.37, 117.73, 99.08,
75.82, 69.70, 66.80, 66.76, 51.57, 44.45, 22.61 ppm; MS (FI, 7 kV, 3 mA, 120ꢁC): m/z (rel.
intensity) ˆ 291.1 (100), 267.2 (18).
Allyl S-(2,3,4,6-tetra-O-acetyl-ꢀ-D-galactopyranosyl)-(1!4)-2-acetamido-4-thio-6-thiocyanato-
2,4,6-trideoxy-ꢁ-D-galactopyranoside (6; C26H36N2O13S2) and Allyl O-(2,3,4,6-tetra-O-acetyl-
ꢀ-D-galactopyranosyl)-(1!3)-(S-(2,3,4,6-tetra-O-acetyl-ꢀ-D-galactopyranosyl)-(1!4))-2-
acetamido-4-thio-6-thiocyanato-2,4,6-trideoxy-ꢁ-D-galactopyranoside (7; C40H54N2O22S2)
A mixture of 122 mg 4 (0.42 mmol), 210 mg Hg(CN)2 (0.84 mmol), 30 mg HgBr2 (0.084 mmol), and
3
ꢁ
Ê
4.0 g molecular sieves (4 A) in 12 cm 1:1 toluenenitromethane was stirred at 60 C. After 1 h, a
solution of 424 mg tetra-O-acetyl-ꢁ-D-galactopyranosyl bromide 5 (1.03 mmol) in 6 cm3
nitromethane was added dropwise over a period of 2 h. The mixture was stirred at 60ꢁC for further
18 h. TLC (toluene/acetone, 2:1) indicated complete disappearance of 4. The molecular sieve was
®ltered off. The solution was diluted with dichloromethane and washed three times with saturated
aqueous NH4Cl solution. The organic layer was separated, dried (MgSO4), and concentrated.
Puri®cation by column chromatography (toluene/acetone, 3:1! 1:1) gave 124 mg 6 (45%) and
72 mg 7 (17%) as colorless crystals.
6: TLC (ethyl acetate): Rf ˆ 0.35; m.p.: 56±57ꢁC; [ꢁ]D20 ˆ ‡67.73 (c ˆ 0.75, CH2Cl2); IR:
ꢃ ˆ 3369.9, 2929.6, 2155.5, 1750.8 cmꢂ1; 1H NMR (400 MHz): ꢂ ˆ 5.84 (m, 2H, H200, NHAc), 5.40
0
00
0
0
0
0
0
0
(dd, 1H, J4 ,5 ˆ 0.62, H4 ), 5.30 (m, 2H, H3 ), 5.14 (t, 1H, J2 ,3 ˆ 9.97, H2 ), 5.00 (dd, 1H,
0
0
0
0
0
J3 ,4 ˆ 3.33, H3 ), 4.805 (d, 1H, J1 ,2 ˆ 9.96, H1 ), 4.795 (d, 1H, J1,2 ˆ 3.95, H1), 4.26 (m, 3H, H2,
H5, H100), 4.07 (m, 3H, H3, H60b, H60a), 4.00 (m, 1H, H100), 3.88 (m, 1H, H50), 3.59 (d, 1H,
JOH,3 ˆ 7.68, OH), 3.41 (dd, 1H, J3,4 ˆ 3.73, J4,5 ˆ 1.66, H4), 3.35 (dd, 1H, J5,6a ˆ 8.51,
J6a,6b ˆ 13.91, H6a), 3.17 (dd, 1H, J5,6b ˆ 4.35, H6b), 2.10 (s, 6H, COCH3), 2.00 (s, 6H, COCH3),
1.91 (s, 3H, COCH3) ppm; 13C NMR (100 MHz): ꢂ ˆ 172.56, 170.35, 170.16, 170.14, 169.90, 132.70
(C200), 119.04 (C300), 111.98 (-SCN), 96.38 (C1), 85.03 (C10), 74.55 (C50), 71.57 (C30), 71.54 (C3),
69.05 (C5), 68.65 (C100), 67.68 (C20), 67.29 (C40), 61.62 (C60), 52.61 (C4), 51.43 (C2), 36.29 (C6),
23.22, 20.77, 20.68, 20.64, 20.50 ppm; MALDI MS (16 kV): m/z ˆ 687.3 (M‡K, 100%).
7: TLC (ethyl acetate): Rf ˆ 0.50; m.p.: 100±102ꢁC; [ꢁ]D20 ˆ ‡53.44 (c ˆ 0.90, CH2Cl2); IR:
ꢃ ˆ 2934.4, 2155.3, 1751.2 cmꢂ1
;
1H NMR (400 MHz): ꢂ ˆ 5.90 (m, 1H, H2000), 5.51 (d, 1H,
0
00
0
0
00 00
JNH,2 ˆ 9.7, NHAc), 5.42 (dd, 1H, J4 ,5 ˆ 0.75, H4 ), 5.41 (dd, 1H, J4 ,5 ˆ 1.1, H4 ), 5.29 (m, 2H,
H30a00, H3e000), 5.14 (dd, 1H, J2 ,3 ˆ 9.8, H2 ), 5.11 (dd, 1H, J2 ,3 ˆ 10.6, H2 ), 5.00 (d, 1H,
0
00
0
0
00 00
00 00
0
0
00
0
0
0
0
J1 ,2 ˆ 10.6, H1 ), 5.00 (dd, 1H, J3 ,4 ˆ 3.3, H3 ), 4.98 dd, 1H, J3 ,4 ˆ 3.7, H3 ), 4.76 (d, 1H,
00
00 00
J1,2 ˆ 3.9, H1), 4.64 (d, 1H, J1 ,2 ˆ 7.9, H1 ), 4.60 (dd, 1H, J2,3 ˆ 10.6, H2), 4.27 (dd, 1H,
J6 a,6 b ˆ 11.4, H6a00), 4.27 (ddd, 1H, J5,6a ˆ 8.3, J5,6b ˆ 4.4, H5), 4.24 (m, 1H, H1000), 4.17 (dd, 1H,
00
00
J6 a,6 b ˆ 11.0, H60b), 4.09 (dd, 1H, H60a), 4.03 (dd, 1H, H60b0), 4.00 (m, 1H, H1000), 3.95 (ddd, 1H,
0
0
J5 ,6 b ˆ 6.5, J5 ,6 a ˆ 7.0, H50), 3.91 (ddd, 1H, J5 ,6 b ˆ 5.9, J5 ,6 a ˆ 6.9, H500), 3.90 (dd, 1H,
J3,4 ˆ 3.6, H3), 3.58 (dd, 1H, J4,5 ˆ 1.8, H4), 3.28 (dd, 1H, J6a,6b ˆ 14.2, H6a), 3.17 (dd, 1H, H6b),
2.21 (s, 3H, COCH3), 2.14 (s, 3H, COCH3), 2.14 (s, 3H, COCH3), 2.03 (s, 3H, COCH3), 2.02 (s, 3H,
COCH3), 2.01 (s, 3H, COCH3), 1.97 (s, 3H, COCH3), 1.96 (s, 3H, COCH3), 1.95 (s, 3H, COCH3)
ppm; 13C NMR (100 MHz): ꢂ ˆ 171.04, 170.28, 170.14, 170.10, 170.06, 170.05, 169.06, 168.81,
132.83 (C2000), 119.24 (C3000), 112.01 (-SCN), 102.59 (C100), 97.04 (C1), 84.01 (C10), 78.62 (C3),
74.20 (C50), 72.25 (C30), 71.52 (C500), 70.48 (C300), 68.85 (C5), 68.80 (C1000), 68.54 (C200), 67.13
0
0
0
0
00 00
00 00

ꢀ-(1!4)-Linked Thiodisaccharides
1143
(C20), 66.99 (C40,C400), 61.40 (C60), 60.99 (C600), 50.86 (C4), 48.40 (C2), 36.16 (C6), 23.50, 20.69,
20.68, 20.65, 20.58, 20.55, 20.50, 20.49, 20.46 ppm; MS (FI, 7 kV, 3 mA, 230ꢁC) m/z (rel.
intensity) ˆ 979.7 (75), 590.4 (100), 331.2 (80).
Methyl S-(2,3,4,6-tetra-O-acetyl-ꢀ-D-galactopyranosyl)-(1!4)-2,3-di-O-acetyl-4,6-dideoxy-4-
thio-6-thiocyanato-ꢁ-D-galactopyranoside (10; C26H35NO15S2)
Compound 8 (60 mg, 0.19 mmol), 48 mg Hg(CN)2 (0.19 mmol), 7 mg HgBr2 (0.019 mmol) and 2.0 g
3
ꢁ
Ê
molecular sieves (4 A) in 6 cm 1:1 toluene/nitromethane were stirred at 60 C for 1 h. Then, 95 mg
tetra-O-acetyl-ꢁ-D-galactopyranosyl bromide 5 (0.23 mmol) in 2 cm3 nitromethane were added
dropwise. After stirring for 20 h at 60ꢁC the mixture was ®ltered (Celite) and concentrated.
Puri®cation by column chromatography (toluene/acetone, 6:1) gave 71 mg 9 (56%) as colorless
crystals and 12 mg recovered starting material 8 (20%).
TLC (toluene/acetone, 3:1): Rf ˆ 0.51; m.p.: 70±71ꢁC; [ꢁ]D20 ˆ ‡97.70 (c ˆ 1.00, CH2Cl2); IR:
1
0
ꢃ ˆ 2917.9, 2154.0, 1743.5 cmꢂ1; H NMR (400 MHz): ꢂ ˆ 5.38 (dd, 1H, J4 ,5 ˆ 0.98, H4 ), 5.32
0
0
0
0
0
(dd, 1H, J3,4 ˆ 4.43, H3), 5.12 (t, 1H, J2 ,3 ˆ 9.85, H2 ), 5.03 (dd, 1H, J2,3 ˆ 10.83, H2), 4.96 (dd,
0
0
0
1H, J3 ,4 ˆ 3.44, H3 ), 4.90 (d, 1H, J1,2 ˆ 3.93, H1), 4.37 (ddd, 1H, J5,6b ˆ 3.93, J5,6a ˆ 8.86, H5),
4.33 (d, 1H, J1 ,2 ˆ 10.34, H1 ), 4.12 (dd, 1H, J6 b,6 a ˆ 11.32, H60b), 4.05 (dd, 1H, H6a0 ), 3.80 (dt, 1H,
0
0
0
0
0
J5 ,6 b ˆ 5.41, J5 ,6 a ˆ 6.89, H50), 3.64 (dd, 1H, J4,5 ˆ 1.47, H4), 3.45 (s, 3H, OCH3), 3.37 (dd, 1H,
J6a,6b ˆ 14.28, H6a), 3.16 (dd, 1H, H6b), 2.15 (s, 3H, COCH3), 2.07 (s, 3H, COCH3), 2.075 (s, 3H,
COCH3), 2.085 (s, 3H, COCH3), 2.095 (s, 3H, COCH3), 1.96 (s, 3H, COCH3) ppm; 13C NMR
(100 MHz): ꢂ ˆ 170.40, 170.19, 170.12, 170.09, 169.98, 169.53, 111.90 (-SCN), 97.29 (C10), 85.26
(C1), 74.90, 71.47, 70.02, 68.57, 67.95, 67.69, 67.20, 61.79 (C60), 55.80 (OCH3), 50.44 (C4), 36.26
(C6), 20.83, 20.78, 20.73, 20.69, 20.64, 20.51 ppm; MS (FI, 7 kV, 3 mA, 200ꢁC): m/z (rel intensity)
666.2 (70), 630.4 (100).
0
0
0
0
Methyl S-(2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl)-(1!4)-4,6-dideoxy-4-thio-6-thiocyanato-
ꢁ-D-galactopyranoside (12; C22H31NO13S2) and Methyl O-(2,3,4,6-tetra-O-acetyl-
ꢀ-D-glucopyranosyl)-(1!2)-(S-(2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl)-(1!4))-
4,6-dideoxy-4-thio-6-thiocyanato-ꢁ-D-galactopyranoside (13; C36H49NO22S2)
Compound 10 (80 mg, 0.36 mmol), 93 mg Hg(CN)2 (0.37 mmol), 13 mg HgBr2 (0.036 mmol) and
3
ꢁ
Ê
2.8 g molecular sieves (4 A) in 7 cm 1:1 toluene-nitromethane were stirred at 60 C for 1 h. Then,
161 mg tetra-O-acetyl-ꢁ-D-glucopyranosyl bromide 11 (0.39 mmol) in 1.5 cm3 nitromethane were
added dropwise over a period of 40 min. The mixture was stirred at 60ꢁC for further 2 h. Then, 91 mg
Hg(CN)2 (0.36 mmol), 13 mg HgBr2 (0.036 mmol), and 80 mg 11 (0.19 mmol) in 1 cm3 nitromethane
were added, and stirring was continued for 14 h. The mixture was ®ltered (Celite) and concentrated.
Puri®cation by column chromatography (toluene/acetone, 3:1!2:1) gave 40 mg 12 (19%) and
33 mg 13 (10%) as colorless crystals.
12: TLC (toluene/acetone, 3:1): Rf ˆ 0.06; m.p.: 81±82ꢁC; [ꢁ]D20 ˆ ‡62.50 (c ˆ 1.30, CH2Cl2);
1
IR: ꢃ ˆ 3468.4, 2941.2, 2155.7, 1753.8 cmꢂ1; H NMR (400 MHz) ꢂ ˆ 5.18 (t, 1H, J3 ,4 ˆ 9.36,
0
0
H30), 5.03 (t, 1H, J4 ,5 ˆ 9.84, H4 ), 4.94 (t, 1H, J2 ,3 ˆ 9.35, H2 ), 4.77 (d, 1H, J1 ,2 ˆ 10.34, H1 ),
0
0
0
0
0
0
0
0
0
4.75 (d, 1H, J1,2 ˆ 3.44, H1), 4.28 (ddd, 1H, J5,6b ˆ 3.94, J5,6a ˆ 8.37, H5), 4.22 (dd, 1H,
J6 b,6 a ˆ 12.31, H60b), 4.13 (dd, 1H, H60a), 4.01 (m, 1H, H2 or H3), 3.68 (ddd, 1H, J5 ,6 b ˆ 1.96,
0
0
0
0
J5 ,6 a ˆ 4.92, H50), 3.62 (m, 1H, H2 or H3), 3.48 (s, 3H, OCH3), 3.46 (dd, 1H, J3,4 ˆ 3.94,
J4,5 ˆ 1.48, H4), 3.30 (dd, 1H, J6a,6b ˆ 13.78, H6a), 3.17 (dd, 1H, H6b), 2.10 (s, 3H, COCH3), 2.05 (s,
3H, COCH3), 2.00 (s, 3H, COCH3), 1.98 (s, 3H, COCH3) ppm; 13C NMR (100 MHz), ꢂ ˆ 170.54,
170.05, 169.49, 169.34, 112.03 (-SCN), 99.44 (C10), 83.63 (C1), 76.02, 73.56, 70.71, 70.68, 70.64,
68.95, 68.12, 61.77 (C60), 55.98 (OCH3), 51.78 (C4), 36.18 (C6), 20.76, 20.68, 20.54 ppm; MS (FI,
7 kV, 3 mA, 190ꢁC) m/z (rel intensity) ˆ 581.2 (80), 331.1 (84), 224.0 (100).
0
0

1144
I. Wenzl et al.
13: TLC (toluene/acetone, 3:1): Rf ˆ 0.19; IR: ꢃ ˆ 2916.9, 2156.8, 1752.9, 1654.4 cmꢂ1
;
1H
NMR (400 MHz): ꢂ ˆ 5.30±4.70 (m, 9H), 4.31 (m, 1H), 4.25±3.96 (m, 5H), 3.73±3.62 (m, 3H), 3.43
(s, 3H, OCH3), 3.42 (m, 1H), 3.30 (dd, 1H, J5,6a ˆ 8.86, J6a,6b ˆ 14.28, H6a), 3.13 (dd, 1H,
J5,6b ˆ 3.94, H6b), 2.62 (d, 1H, JOH,3 ˆ 4.43, OH), 2.10 (s, 3H, COCH3), 2.09 (s, 3H, COCH3), 2.07
(s, 3H, COCH3), 2.06 (s, 3H, COCH3), 2.02 (s, 3H, COCH3), 2.01 (s, 3H, COCH3), 2.00 (s, 3H,
COCH3), 1.98 (s, 3H, COCH3) ppm.
Methyl O-(2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl)-(1!2)-(S-(2,3,4,6-tetra-O-acetyl-ꢀ-D-
glucopyranosyl)-(1!4))-3-O-acetyl-4,6-dideoxy-4-thio-6-thiocyanato-ꢁ-D-galactopyranoside
(14; C38H51NO23S2)
Compound 13 (23 mg, 25.2 mmol) was dissolved in 1.0 cm3 pyridine and 0.2 cm3 acetic anhydride. A
catalytic amount of DMAP was added, and the solution was stirred for 4 h at room temperature.
Coevaporation of the solvent with toluene in vacuo and puri®cation by column chromatography gave
18 mg 14 (75%) as colorless crystals.
TLC (toluene/acetone, 3:1): Rf ˆ 0.37; m.p.: 84±86ꢁC; [ꢁ]D20 ˆ ‡38.30 (c ˆ 0.60, CH2Cl2); IR:
ꢃ ˆ 2941.9, 2156.0, 1755.1 cmꢂ1; 1H NMR (400 MHz): ꢂ ˆ 5.21 (dd, 1H, J3,4 ˆ 4.5, H3), 5.17 (t, 1H,
00
0
0
00
00 00
0
0
00 00
J3 ,4 ˆ 9.4, H3 ), 5.16 (t, 1H, J3 ,4 ˆ 9.5, H3 ), 5.05 (dd, 1H, J4 ,5 ˆ 10.1, H4 ), 5.00 (dd, 1H,
00
0
0
0
00 00
0
0
J4 ,5 ˆ 10.0, H4 ), 4.97 (dd, 1H, J2 ,3 ˆ 9.5, H2 ), 4.90 (dd, 1H, J2 ,3 ˆ 9.3, H2 ), 4.82 (d, 1H,
00
00 00
J1,2 ˆ 3.8, H1), 4.62 (d, 1H, J1 ,2 ˆ 7.9, H1 ), 4.36 (ddd, 1H, J5,6a ˆ 9.0, J5,6b ˆ 3.7, H5), 4.34 (d,
1H, J1 ,2 ˆ 10.0, H1 ), 4.22 (dd, 1H, J6 b,6 a ˆ 12.5, H60b), 4.19 (dd, 1H, J6 a,6 b ˆ 12.5, H6a00), 4.18
0
0
0
0
0
00
00
(dd, 1H, H60b0), 4.08 (dd, 1H, H60a), 3.71 (dd, 1H, J2,3 ˆ 10.4, H2), 3.67 (ddd, 1H, J5 ,6 a ˆ 5.4,
00 00
J5 ,6 b ˆ 2.6, H500), 3.59 (dd, 1H, J4,5 ˆ 1.8, H4), 3.57 (ddd, 1H, J5 ,6 a ˆ 5.6, J5 ,6 b ˆ 2.2, H50), 3.45
(s, 3H, OCH3), 3.33 (dd, 1H, J6a,6b ˆ 14.3, H6a), 3.13 (dd, 1H, H6b), 2.12 (s, 3H, COCH3), 2.11 (s,
3H, COCH3), 2.09 (s, 3H, COCH3), 2.08 (s, 3H, COCH3), 2.015 (s, 3H, COCH3), 2.01 (s, 3H,
COCH3), 2.00 (s, 3H, COCH3), 1.98 (s, 3H, COCH3), 1.98 (s, 3H, COCH3) ppm; 13C NMR
(100 MHz): ꢂ ˆ 168.74, 169.20, 169.30, 169.95, 170.09, 111.92 (-SCN), 101.40 (C100), 99.41 (C1),
84.45 (C10), 76.21 (C50), 75.51 (C2), 73.42 (C30), 72.72 (C300), 72.02 (C500), 71.51 (C200), 70.92
(C20), 70.78 (C3), 68.27 (C400), 68.08 (C40), 67.79 (C5), 61.84 (C600), 61.79 (C60), 55.91 (OCH3),
50.86 (C4), 36.27 (C6), 20.85, 20.78, 20.74, 20.71, 20.54 ppm; MS (FI, 7 kV, 3 mA, 220ꢁC): m/z (rel.
intensity) ˆ 953.6 (100), 894.7 (8), 331.2 (35), 218.1 (30).
00 00
0
0
0
0
Acknowledgements
È
This work was supported by the Jubilaumsfonds of the Austrian National Bank (Project Nos. 6011 to
(F.M.U.) and 4663 (to W.S.)).
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Received February 22, 1999. Accepted March 18, 1999