SYNTHESIS OF ISOHARRINGTONINE AND SEPARATION OF THE ISOMERS

Isoharringtonine (1), one of the four cephalotaxine esters exhibiting antitumor activity was synthesized by first treating the cephalotaxine ester of keto acid with α-benzyloxy-α-bromoacetic acid ester instead of the classical α-bromoacetic acid in the Reformatsky reaction to give a mixture of four stereoisomers. The mixture could only be separated into two parts A and B by chromatotron. A and B were hydrogenated separately with Pd/C. The reaction products obtained were separated on chromatotron to give A_H1, A_H2 and B_H1, B_H2 correspondingly. The m p, α and various spectra of B_H1 are indentical with those of the natural isoharringtonine. The configurations of the rest three isomers were postulated based upon their NMR spectra in combination with comformational analysis.