The total syntheses of aflastatin A (1, AsA) and its C3–C48 degradation fragment (2a, R = H) have been accomplished. The syntheses feature several complex diastereoselective fragment couplings, including a Felkin-selective trityl-catalyzed Mukaiyama aldol reaction, a chelate-controlled aldol reaction involving soft enolization with magnesium, and an anti-Felkin-selective boron-mediated oxygenated aldol reaction. Careful comparison of the spectroscopic data for the synthetic C3–C48 degradation fragment to that reported by the isolation group revealed a structural misassignment in the lactol region of the naturally derived degradation product. Ultimately, the data reported for the naturally derived AsA C3–C48 degradation lactol (2a, R = H) was attributed to its derivative lactol trideuteriomethyl ether (2b, R = CD3). Additionally, the revised absolute configurations of six stereogenic centers (C8, C9 and C28–C31) were confirmed.

Total synthesis of aflastatin A

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.