The first semi-synthesis of enantiopure homoharringtonine via anhydrohomoharringtonine from a preformed chiral acyl moiety

(2'R,3S,4S,5R)-(-)-Homoharringtonine 2 was synthesized by direct esterifica tion of cephalotaxine, using the activated forms of suitably substituted te trahydropyrancarboxylic acids as sterically compact chiral side-chain precu rsors, followed by selective ring opening of the resulting (2'R,3S,4S,5R)-( -)-anhydrohomoharringtonine 6. Both enantiomers of the anhydro acyl moiety were prepared either by asymmetric alpha-hydroxyalkylation of the suitably substituted ethylenic alpha-ketoester 7 followed by acidic cyclisation, or by resolving the corresponding racemic mixture via formation of diastereome rs with (-)quinine. Racemic cephalotaxine, as well as both its enantiomers, were prepared from natural -partially racemized- (-)-cephalotaxine 1. (C) 1999 Elsevier Science Ltd, All rights reserved.