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

摘要

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.