Synthesis of D-Galactopyranosides of trans-4-Hydroxy-L-proline Utilizing the Sulfoxide Glycosylation Method

Abstract

Phenyl 1-thio-β-D-galactopyranoside (1) was converted into two sulfoxide glycosyl donors: phenyl (2,3,4,6-tetra-O-benzyl)-1-thio-β-D-galactopyranoside S-oxide (3) and phenyl (2,3,4,6-tetra-O-pivaloyl)- 1-thio-β-D-galactopyranoside S-oxide (5). These glycosyl donors were then each reacted with Na- fluorenylmethoxycarbonyl-trans-4-hydroxy-L-proline allyl ester (7). The glycosylation reactions were conducted at -70°C with triflic anhydride as promotor, in the presence of 2,6-di-tert-butyl-4-methylpyridine. In the case of the perbenzylated sulfoxide donor (3), the major product was Na-fluorenylmethoxycarbonyl-trans-4-hydroxy- 4-O-[(2,3,4,6-tetra-O-benzyl)-a-D-galactopyranosyl]-L-proline allyl ester (8a). In dichloromethane, the a-to-β ratio was 3 : 1 and in toluene this improved to 5 : 1, with a combined yield of 41%. In the case of the perpivaloylated sulfoxide donor (5), Na-fluorenylmethoxycarbonyl-trans-4-hydroxy-4-O-[(2,3,4,6-tetra-O-pivaloyl)-β-D- galactopyranosyl]-L-proline allyl ester (9) was obtained as the sole glycoside product in 46% yield.