STUDIES ON THE SYNTHESIS OF AUREOLIC ACID ANTIBIOTICS - HIGHLY STEREOSELECTIVE SYNTHESIS OF ARYL 2-DEOXY-BETA-GLYCOSIDES VIA THE MITSUNOBU REACTION AND SYNTHESIS OF THE OLIVOMYCIN A-B DISACCHARIDE

The Mitsunobu reaction of phenols and 1,2-cis-2-thiophenyl-alpha-D-gly copyranoses or 1,2-cis-2-selenophenyl-alpha-D-glycopyranoses is a very effective method for the highly stereoselective synthesis of aryl 2-d eoxy-beta-D-glycosides. The equatorial 2-thiophenyl or 2-selenophenyl- substituents are easily removed by Bu(3)SnH reduction following the g lycosidation reaction to provide the aryl 2-deoxy-beta-D-glycosides in good to excellent yield. The aryl beta-D-glycosides are obtained with 6.5:1 selectivity in the least selective case(Table 1) and up to >20: 1 selectivity in others. The reaction appears to be S-N(2)-like in cha racter (see 30), in that the beta:alpha reaction stereoselectivity cor relates well with the alpha:beta anomeric composition of the pyranose starting material. The equatorial 2-thiophenyl or 2-selenophenyl subst ituents play an important role by increasing the alpha:beta anomer rat io of the pyranose starting materials. The reactions do not appear to proceed by way of free oxonium ions such as 17, since several reaction s in which 17 was deliberately generated (e.g., TMS-OTf promoted react ions of glycosyl acetate 14, BF3 . Et(2)O catalyzed reactions of imida te 15) gave at best 1:1 mixtures of alpha- and beta-glycosides, and in several cases gave alpha-glycosides with >10:1 selectivity. These dat a also rule out the involvement of episulfonium ion 18 as a kineticall y significant intermediate in reactions that proceed by way of oxonium ion 17. A short and highly effective synthesis of reducing disacchari de 53 from D-fucal was developed. This functionalized disaccharide rea dily undergoes Mitsunobu glycosidation with 2-naphthol, providing the model naphthyl A-B disaccharide 5 with 11:1 beta,alpha:alpha,alpha sel ectivity. Finally, olivin precursor 63 has also been glycosylated with 53, providing the advanced synthetic intermediate 6 with excellent di astereoselectivity.