A stereoselective synthesis of the polyene fragment C(53)-C(67) of amphidinol 3 is described using a sequence of reduction, benzoylation, and reductive elimination for the stereospecific preparation of the polyene motif as key steps starting from acetylenic precursors.

As part of a project directed toward the total synthesis of the tetracyclic diterpene 3α‐hydroxy‐15‐rippertene, a constituent of the defense secretion of higher termites, a fast access to two advanced hydroazulene key intermediates has been achieved by starting from (–)‐isopulegol. A regio‐ and diastereoselective formal hydromethallylation and a regioselective ring expansion served as the key steps in the formation of the seven‐membered ring. Completion of the bicyclic title compounds was then achieved by cyclopentene annulation through diastereoselective conjugate addition of organocuprates and subsequent intramolecular aldol condensations.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

The C53-C67 and C53-C65 polyene fragments of amphidinols have been synthesized in an efficient and convergent fashion from sorbic acid in good overall yields (30-31%) by employing a chemoselective cross-metathesis of a Weinreb amide and a Julia-Kocienski olefination as the key steps.

The C18-C30 fragment of amphidinol 3 has been synthesized in a convergent fashion by employing two asymmetric Sharpless dihydroxylations, a Julia-Kocienski olefination and a Wittig reaction as the key steps.

The diastereoselective synthesis of the C17-C30 fragment of amphidinol 3 (AM3) 1 was achieved from the enantio-enriched aldehyde 20, Weinreb amide 14 and 2-bromo-3-(trimethylsilyl)propene, which was used as a bifunctional conjunctive reagent. The absolute configuration of the stereogenic centers, in both aldehyde 20 and Weinreb amide 14, were efficiently controlled by using (+)-(R)-methyl-p-tolylsulfoxide as the unique source of chirality.