Postulated Biogenesis-Guided Total Synthesis and Structural Revision of 2,18- seco-Lankacidinol A

Abstract

The macrocyclic structure of 2,18-seco-lankacidinol A, a newly isolated antitumor antibiotic, has been revised on the basis of a concise modular synthesis inspired by a reconsidered biosynthetic proposal. Notable features include (1) an acid-promoted intramolecular transacetalization of a N-lactoyl-O-methyl-N,O-acetal to construct the 4-oxazolidinone ring and (2) late-stage β-keto imide aldolizations that give rise to facile, stereodivergent access to all lactonic diastereomers.