PT72242A - Process for the preparation of apovincaminic acid ester derivatives - Google Patents

Abstract

Prepn. of halo-vincaminic acid esters (Ia) and halo-apovincaminic acid esters (Ib), i.e. 9,10 -X, R1 esters with the ethyl group opt. replaced by a gp. R2, (where R1,R2 are 1-6C alkyl and X is halo) and their acid addn. salts and optical antipodes, by treatment of a 14-oxo-15-hydroxy-E-homoeburnane (II), its epimers, optical antipodes or acid addn. salts, with an oxidising agent to give a 14,15-dioxo-E-homo-eburnane, (III). (III) or a 14-oxo-15-hydroxyimino-E-homo-eburnane deriv., (IV), formed by reaction of (III) with hydroxylamine or its salts) or their salts or optical isomers is reacted with the alcohol R1-OH in the presence of an alkaline agent to form the halo-vincaminic acid ester (Ia). (Ia) may be converted to an acid addn. salt, resolved or hydrolysed to give the free acid, (V). (V) or (IV), or its acid addition salt or optical isomers, may be treated with the alcohol R1-OH in the presence of a dehydrating conc. acid to form (Ib), which may be converted to its acid addn. salts or resolved. Useful as anti-hypoxia and cerebral protecting agents, which increase cerebral oxygenation improving mental alertness etc. Unlike known preparations, the present process allows production of (Ia) and (Ib) from easily prepared starting materials, by simple processes, giving good yields and purity.