Synthesis of Functionalized Thiodisaccharides by Conjugate Addition

Abstract

Oligosaccharides containing thioglycosidic linkages are resistant to enzyme-catalysed hydrolysis and therefore interesting material for studies of carbohydrate hydrolases. Some of these were shown to be competitive inhibitors for several glycanases such as α-amylase,¹ cellobiohydrolase I and II,² and for α-l-fucosidase,³ a glycosidase. Thio-oligosaccharides have also been used to prepare column material for affinity chromatography to isolate carbohydrate hydrolases. In contrast, affinity material containing normal O-glycosidic bonds was hydrolysed and led to column deterioration. By employing this approach, affinity materials containing 1,4-dithiocellobiose and 1,4,4′-trithiocellotriose could be used successfully to separate the cellobiohydrolases of Trichoderma reesei.²

Notes

Typical procedure: The saccharide acceptor (0.5 mmol) and the thioglucose (1, 200 mg, 0.57 mmol) were stirred in chloroform (10 mL) at room temperature and triethylamine (2 μL) was added. Stirring was continued for 30 min, the solvent evaporated and the raw material purified by crystallisation or chromatography.

Representative physical data: (3) mp 161–164 °C, [α]_D ²⁰ −125° (c 1, chloroform), ¹H NMR (400 MHz, CDCl₃): δ 5.14 (s, 1 H, H-1), 4.59 (d, 1 H, J_1′,2′ = 10.2 Hz, H-1′), 3.98–4.06 (m, 2 H, H-6endo and H-6exo), 3.58 (m, 1 H, H-4), 3.09 (dd, 1 H, J_3eq.4 = 8.1 Hz, J_gem = 17.8 Hz, H-3eq), 2.04 (dd, 1 H, J_3ax,4 = 1.5 Hz, H-3ax). (5) mp 56 °C, [α]_D ²⁰ +43° (c 1, chloroform), ¹H NMR (400 MHz, CDCl₃). δ 4.99 (d, 1 H, J_1,2 = 4.4 Hz, H-1), 4.65 (d, 1 H, J_1′.2′ = 10.1 Hz, H-1′), 4.11 (dd, J_5.6a = 1.9 Hz, H-5), 3.43 (s, 3 H, OMe), 3.41 (dd, 1-H, J_gem = 9.2 Hz, H-6a), 3.32 (dd, 1 H, H-6b), 3.25 (dt, 1 H, J_2.3ax = 8.2 Hz, H-2), 2.61 (m, 2 H, H-3ax and H-3eq); (7) ¹H NMR (400 MHz, CDCl₃): δ = 5.16 (dd, 1 H, J_1,2ax = 12.2 Hz, J_1.2eq = 3.1 Hz, H-1), 4.65 (d, 1 H, J_1,2 = 9.6 Hz, H-1′), 4.38 (d, 1 H, J_4.5 = 10.2 Hz, H-4), 4.06 (dd, 1 H, J_5.6a = 5.6 Hz, J_gem = 10.2 Hz, H-6a), 3.94 (dd, 1 H, J_5.6b = 10.2 Hz, H-6b), 3.59 (ddd, 1 H, H-5), 2.80 (dd, 1 H, J_gem = 14.8 Hz, H-2ax), 2.71 (dd, 1 H, H-2eq), 1.52 (s, 3 H, CH₃), 1.50 (s, 3H, CH₃).