Total synthesis of guanacastepene a: a route to enantiomeric control.
[reaction: see text] The goal of the total synthesis of guanacastepene A served as a focus to bring together several chemical inquiries. One involved the synthesis of fused 5,7-hydrazulenones (see structure 20). Another issue had to do with the mechanistic intermediates in reductive cyclizations (see 17 to 18 and 19). The total synthesis required a mastery of an intramolecular Knoevenagel condensation of a beta,gamma-unsaturated ketone (see compound 41). Actually, cyclization was best accomplished when the terminal double bond of 41 was first converted to an epoxide. Further issues related to the stereochemistry at C5 and, rather surprisingly, the propensity for beta-face acetoxylation at C13. Crystallographic verification of the assigned beta-stereochemistry at C13 is provided. Finally, a route to optically active material is provided (see compound 20). A key element in this construction was an enantioselective addition of isopropenyl cuprate to 2-methylcyclopentenone (see compound 99).
Mandal
Mihirbaran
M
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, Box 106, New York, New York 10021, USA.
Yun
Heedong
H
Dudley
Gregory B
GB
Lin
Songnian
S
Tan
Derek S
DS
Danishefsky
Samuel J
SJ
D003461:Crystallography; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
D004224:Diterpenes; C454620:guanacastepene A