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



We 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)