Method of preparing vincristine

In the chromic oxide-acetic acid oxidation of vinblastine to vincristine, the improvement which comprises employing tetrahydrofuran as the solvent for VLB base.

The method of preparing a compound of the formula ##STR3## wherein, R is OH or acetoxy, R.sup.4 is CHO, and when taken singly, one of R.sup.1 and R.sup.2 is H or OH and the other is C.sub.2 H.sub.5 and R.sup.3 is H and, when taken together, R.sup.2 and R.sup.3 with a bridging oxygen atom represent an .alpha.-epoxide and R.sup.1 is C.sub.2 H.sub.5 ;

• which comprises dissolving a compound according to Formula II, in which R.sup.4 is CH.sub.3 and R, R.sup.1, R.sup.2 and R.sup.3 have the same significance as before, in tetrahydrofuran and contacting said solution with an aqueous chromate-sulfuric acid solution at a reaction temperature in the range from about -80.degree. C. to about -50.degree. C.

A process for preparing VCR and formylleurosine which comprises oxidizing a tetrahydrofuran solution of the crude dimeric indole-dihydroindole alkaloids obtainable by extraction from the leaves of Vinca rosea in which VLB and leurosine are the predominant alkaloids with an aqueous chromate-sulfuric acid oxidizing solution at a temperature in the range about -80.degree. C. to about -50.degree. C. until substantially all the VLB and leurosine initially present are converted to vincristine and formylleurosine respectively, optionally reformylating any 1-desformyl congeners present, and then separating vincristine and formylleurosine therefrom by chromatography.