Pd-catalyzed asymmetric hydroalkoxylation of tertiary alcohol

Abstract

MasterMono- and oligosaccharides, containing tertiary alcohol at anomeric center, are core moieties of many naturally-occurring compounds exhibiting biological activity as antitumor agents. The synthesis of these oligosaccharides through classical glycosylation method has been a difficult task because of steric bulk arising from tertiary moiety and hence not a suitable candidates as glycosyl acceptors. Moreover, the stereoselective synthesis of β-anomer is thermodynamically unfavorable because of inherent preference for α-anomer due to anomeric effect. Therefore, the development of an efficient stereoselective synthetic route of oligosaccharides containing tertiary alcohol at anomeric position is important. In this thesis, we have demonstrated a novel stereoselective method to synthesize these sugars having tertiary alcohol at anomeric position by using strong base with the previously optimized palladium-catalyzed hydroalkoxylation conditions developed by Rhee’s group. Surprisingly, we observed the inversion of anomeric stereocenter of newly formed O,O-acetal bond, which is in contrast to results reported by Rhee’s group. Our initial goal is to synthesize Amicenomycin B, an antibiotic and antimicrobial agent, containing a trisaccharide attached via β-linked tertiary alcohol. Despite a number of useful biological applications, there are no reports on the synthesis of Amicenomycin B. The model studies towards the synthesis of Amicenomycin B is demonstrated in this thesis. We anticipate that this new protocol will inspire future endeavors in synthesizing and finding new bioactive oligosaccharides that contain tertiary alcohol at the anomeric center