Stereoselective synthesis of (-)-cephalotaxine and C-7 alkylated analogues.
A total asymmetric synthesis of (-)-cephalotaxine is reported. The chemistry of alpha,beta-unsaturated gamma-lactams was used to access the 1-azaspiro[4.4]nonane skeleton in enantiomerically pure form via a stereocontrolled semipinacolic rearrangement of an alpha-hydroxyiminium ion. This spiro compound was transformed into (-)-cephalotaxine without any racemization or epimerization by following the racemic synthesis reported by Kuehne. We thus performed a total synthesis of (-)-cephalotaxine in 98.7% ee with an overall yield of 9.8% over a 16 steps sequence. This synthetic process was adaptable to the access of some alkylated analogues.
Planas
Loïc
L
UMR 8638 (CNRS-Université Paris-5), Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Pérard-Viret
Joëlle
J
Royer
Jacques
J
D000478:Alkylation; D001372:Aza Compounds / Q000737:chemistry; D006248:Harringtonines / Q000138:chemical synthesis*; D000077863:Homoharringtonine; D007097:Imines / Q000737:chemistry; D007769:Lactams / Q000737:chemistry; D015394:Molecular Structure; D013141:Spiro Compounds / Q000737:chemistry; D013237:Stereoisomerism
D001372:Aza Compounds; D006248:Harringtonines; D007097:Imines; D007769:Lactams; D013141:Spiro Compounds; D000077863:Homoharringtonine