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

Article abstract of DOI:10.1016/S0040-4039(99)00327-5

(2'R,3S,4S,5R)-(-)-Homoharringtonine 2 was synthesized by direct esterification of cephalotaxine, using the activated forms of suitably substituted tetrahydropyrancarboxylic acids as sterically compact chiral side-chain precursors, 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 α-hydroxyalkylation of the suitably substituted ethylenic α-ketoester 7 followed by acidic cyclisation, or by resolving the corresponding racemic mixture via formation of diastereomers with (-)quinine. Racemic cephalotaxine, as well as both its enantiomers, were prepared from natural - partially racemized - (-)- cephalotaxine 1.