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Synlett 2006(11): 1711-1714  
DOI: 10.1055/s-2006-947338
LETTER
© Georg Thieme Verlag Stuttgart · New York

New Oligosaccharide Analogues: Non-Glycosidically Linked Thioether-­Bridged Pseudodisaccharides

Ian Cumpstey*
Department of Organic Chemistry, Stockholm University, The Arrhenius Laboratory, 106 91 Stockholm, Sweden
Fax: +46(8)154908; e-Mail: cumpstey@organ.su.se;
Further Information

Publication History

Received 24 March 2006
Publication Date:
04 July 2006 (online)

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Abstract

The synthesis of six disaccharide analogues is reported. The pseudodisaccharides each consist of two monosaccharide residues linked non-glycosidically via a thioether functionality; both C 2-symmetric and unsymmetrically substituted examples are described. The synthesis was achieved by first introducing an acetate-protected sulfur into partially protected carbohydrates by SN2 displacement of sulfonate esters by thioacetate. Deacetylation of the sulfur was followed by treatment with another carbohydrate sulfonate derivative, and a second SN2 displacement gave the pseudodisaccharide products.

Key words

carbohydrates - sulfur - stereoselective synthesis - coupling - pseudodisaccharides

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Typical Data - (Methyl 3- O -Benzyl-4,6- O -benzylidene-2-deoxy-β-d-mannopyranos-2-yl) (Methyl 2,3,4-Tri- O -benzyl-6-deoxy-α-d-mannopyranos-6-yl) Sulfane ( 12). A colourless oil; [α]D 23 -2.0 (c 0.5 in CHCl3). 1H NMR (400 MHz, CDCl3): δ = 2.98 (1 H, m, H-6a), 3.27-3.32 (2 H, m, H-5b, H-6′a), 3.34, 3.47 (6 H, 2 × s, 2 × OCH3), 3.55 (1 H, dd, J 1,2 = 1.5 Hz, J 2,3 = 4.4 Hz, H-2b), 3.76-3.88 (6 H, m, H-2a, H-3a, H-4a, H-5a, H-3b, H-6b), 4.07 (1 H, at, J = 9.4 Hz, H-4b), 4.28 (1 H, dd, J 5,6 ′ = 4.8 Hz, J 6,6 ′ = 10.4 Hz, H-6′b), 4.48 (1 H, d, H-1b), 4.60, 4.93 (2 H, ABq, J AB = 11.1 Hz, PhCH2), 4.60 (2 H, s, PhCH2), 4.69-4.80 (5 H, m, H-1a, 2 × PhCH2), 5.58 (1 H, s, PhCH), 7.21-7.48 (25 H, m, Ar-H). 13C NMR (100 MHz, CDCl3): δ = 36.1 (t, C-6a), 53.0 (d, C-2b), 55.0, 57.2 (2 × q, 2 × OCH3), 67.9 (d, C-5b), 68.8 (t, C-6b), 72.2, 72.4, 73.0, 75.2 (4 × t, 4 × PhCH2), 72.5, 75.0, 77.2, 78.1, 80.5 (5 × d, C-2a, C-3a, C-4a, C-5a, C-3b), 80.0 (d, C-4b), 99.0 (d, C-1a), 101.6 (d, PhCH), 103.2 (d, C-1b), 126.2, 127.7, 127.7, 127.8, 127.9, 128.0, 128.3, 128.4, 128.5, 129.0 (10 × d, Ar-CH), 137.7, 138.5, 138.5, 138.7, 138.5 (5 × s, 5 × Ar-C). MS (MALDI): m/z = 874 [M + K+], 858 [M + Na+].

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Typical Procedure for the Formation of Thioether-Bridged Pseudodisaccharides.
Thioacetate 7-9 (0.1-0.4 mmol) was dissolved in MeOH (3 mL) and the solution was degassed and put under argon. MeONa (3 equiv) was added, and the mixture was stirred at r.t. After complete conversion to the thiol, as shown by TLC (approx 1 h), the mixture was poured into NH4Cl (30 mL of a sat. aq solution) and extracted with CH2Cl2 (2 × 20 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. Sulfonate 1-3 (1.5 equiv) was dissolved in DMF (4 mL) and added to the crude thiol. NaH (60% in oil, 2 equiv) was added, and the mixture stirred at 50 °C under argon. After TLC showed the complete disappearance of thiol (approx. 30 min), the mixture was poured into NH4Cl (25 mL of a sat. aq solution) and extracted with Et2O (3 × 25 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (pentane, EtOAc) to afford the thioether-linked pseudodisaccharide 10-15 (see Table [1] ).