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Total Synthesis of (−)-Heptemerone B and (−)-Guanacastepene E

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posted on 27.12.2006, 00:00 by Aubry K. Miller, Chambers C. Hughes, Joshua J. Kennedy-Smith, Stefan N. Gradl, Dirk Trauner
A concise, stereoselective, and convergent total synthesis of the unnatural enantiomer of the neodolastane diterpenoid heptemerone B has been completed. Saponification of (−)-heptemerone afforded (−)-guanacastepene E. The absolute stereochemistry of (−)-heptemerone B was thus established as 5-(S), the same as (−)-guanacastepene E. The longest linear sequence of the synthesis comprises 17 (18) steps from simple known starting materials. Our general synthetic approach integrates a diverse set of reactions, including an intramolecular Heck reaction to create one quaternary stereocenter and a cuprate conjugate addition for the establishment of the other. The central seven-membered ring was closed with an uncommon electrochemical oxidation, whereas the five-membered ring was formed through ring-closing metathesis. The absolute configuration of the two key building blocks was established through an asymmetric reduction and an asymmetric ene reaction.