Natural Product Synthesis Featuring Intramolecular Diels–Alder Approaches – Total Syntheses of Tubelactomicins and Spiculoic Acid A

Abstract

AbstractWe have recently accomplished the total syntheses of the antimicrobial tricyclic 16‐membered macrolides (+)‐tubelactomicin A, B, D, and E by common synthetic approaches based on intramolecular Diels–Alder (IMDA) reactions. These total syntheses established the relative and absolute configurations of three antibiotics – (+)‐tubelactomicins B, D, and E – for which only planar structures had been previously reported. In addition, we have very recently accomplished the total synthesis of a marine natural product, (+)‐spiculoic acid A, by an IMDA strategy. This Microreview summarizes our total syntheses of the four tubelactomicns and the total synthesis of (+)‐tubelactomicin A by Tatsuta et al. Both approaches were based on the use of stereoselective IMDA reactions for the construction of the lower‐half segments of the antibiotics. Total syntheses of the unnatural (–) and natural (+) enantiomers of spiculoic acid A, the former achieved by Baldwin and Lee's group and the latter achieved by the author's group, are also summarized. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)