Synthesis of Thiodisaccharides by Ring Opening of Epoxides from Unsaturated Sugars

OSCAR VARELA; VERÓNICA ELENA MANZANO; MARÍA LAURA UHRIG

Whistler, British Columbia, Canada

Simposio; XXIIIrd International Carbohydrate Symposium; 2006

International Carbohydrate Organization (ICO)

Thiodisaccharides are considered useful tools in inhibition studies of glycoside hydrolases due to their high stability in comparison to their naturally occurring counterparts. We have reported a straightforward synthesis of 3-deoxy-4-thiodisaccharides by reaction of sugar-derived dihydropyranones with isothiouronium salts of aldoses.1 We describe here the epoxidation of unsaturated derivatives of sugars and the opening of the oxirane ring by 1-thioaldoses as an approach for the construction of the interglycosidic linkage of thiodisaccharides. The double bond of the sugar enone 1 was oxidized with t-BuOOH/DBU to give highly diastereoselectively 2, the product having the oxirane ring on the face opposite to the anomeric substituent (ratio 2:3 >10:1). Similarly, epoxidation of 2-hydroxy-3-enopyranoside 4, obtained from 1, with an excess of m-CPBA in CHCl3 afforded selectively the epoxide 5 in 75% yield. In contrast, no appreciable stereoselectivity was observed for the epoxidation of 7, the acetylated derivative of 4. In this case, the epoxides 8 and 9 were obtained in a ~1:1 ratio. Nucleophilic attack of 1-thioaldopiranoses 10 or 11 to the oxirane ring of 2, in the presence of Et3N, led respectively to the glycosides of 3-S-glycopyranosyl-3-thiohex-3-enopyranosid-2-ulose 12 or 13. The ring opening reaction was followed by b-elimination, in order to restore the a,b-unsaturated system. On the other hand, treatment of 4 and 10 in a solution of NaOMe-MeOH, followed by acetylation, led to the thiodisaccharides 14 and 15 (~10:1 ratio), analogs of Glc(1-3)Glc (laminarabiose) and Glc(1-4)Gul.