Straightforward synthesis of modified 4-thiodisaccharides

MARíA LAURA UHRIG; VERóNICA ELENA MANZANO; OSCAR VARELA

Glasgow, Reino Unido

Simposio; 22nd International Carbohydrate Symposium; 2004

International Carbohydrate Organization (ICO)

Thiooligosaccharides constitute an important class of modified sulfur analogs of naturally occurring oligosacharides. These thiosugars are gaining attention because of their potentialities in glycotherapy, and they have been used as convenient probes for enzyme-inhibition studies. As previous works from our and other laboratories have shown that the Michael addition of a sulfur nucleophile to a sugar-derived enone was very efficient and highly diastereoselective, we employed this approach for the synthesis of thiodisaccarides 6, 7, 12 and 13. The sugar enone (1) was obtained with an excellent yield by the tin(IV) chloride-promoted glycosylation of 2-acetoxy-3,4,6-tri-O-acetyl-D-galactal. The 1-thiosugar derivatives 2 and 8 were synthesized by means of the well-known procedure based on the preparation of the isothiouronium salt from the glycosyl bromide, followed by treatment with sodium carbonate. Michael addition of 2 or 8 to 1 led respectively to the alkyl 3-deoxy-4-S-(tetra-O-acetyl-â-D-glycopyranosyl)-4-thio-á-D-threo-hexopyranosid-2-uloses (3 and 9). The formation of the sulfur-containing interglycosidic linkage was highly diastereoselective, and took place from the side of the molecule opposite to the anomeric substituent. The reduction of the carbonyl group of 3 and 9 led to the acetylated derivatives of thiodisaccharides 4, 5 and 10, 11, respectively. The selectivity of this reaction was affected by the reducing agent employed (i.e., NaBH4 reduction of 9 gave 10 and 11 in ~3:1 ratio; whereas such a ratio was ~1:3, when K-selectride was used). The O-deacetylation of 4, 5 and 10, 11 led respectively to the corresponding thiodisaccharides 6, 7 and 12, 13. Enzyme studies (inhibitory activity of glycosidases) have been conducted.