Total synthesis of (-)-heptemerone B and (-)-guanacastepene E.
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.
Miller
Aubry K
AK
Department of Chemistry, University of California-Berkeley, Berkeley, CA 94720-1460, USA.
Hughes
Chambers C
CC
Kennedy-Smith
Joshua J
JJ
Gradl
Stefan N
SN
Trauner
Dirk
D
D003500:Cyclization; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D004224:Diterpenes; C409194:guanacastepene; C516934:heptemerone B