Stereoselective Synthesis of (−)-Cephalotaxine and C-7 Alkylated Analogues
- 1 April 2004
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 69 (9) , 3087-3092
- https://doi.org/10.1021/jo049884l
Abstract
A total asymmetric synthesis of (−)-cephalotaxine is reported. The chemistry of α,β-unsaturated γ-lactams was used to access the 1-azaspiro[4.4]nonane skeleton in enantiomerically pure form via a stereocontrolled semipinacolic rearrangement of an α-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.Keywords
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