During this decade, the enantio- and stereoselective synthesis of natural products has been actively explored in the author's laboratory. In this account, the author outlines practical syntheses of the polycyclic substructures of two novel structurally formidable antibiotics, namely, the trans-fused octahydronaphthalene moiety of versipelostatins and the A/B/C-tricyclic decahydrofluorene moiety of GKK1032s. Both syntheses have been achieved with remarkable regio- and stereoselectivity via intramolecular Diels–Alder reactions using well-designed enantiomeric substrates.

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)