| 摘要 |
<p>Process for the preparation of optical antipodes of 14-oxo-E-homo-eburnane derivs. of formulae (Ia) and (Ib) and their acid addition salts (where R1 is 1-6C alkyl). Several of the cpds. are new including:- i) (Ia), (+)-14-oxo-E-homo- eburnane (3beta,16alpha) is specifically claimed. ii) 14-Hydroxy- deshydro-E-homo-eburnane-5-carboxylic acid derivs. of formula (VII), 14-oxo-deshydro-E-homo-eburnane-5-carboxylic acid derivs. (VIII), (IXa), (IXb), (Xa), (Xb), (XI), (XII), (XIII), (IV) (except when R2 is a 3C atom alkyl) and (V) (except when R2 is a 3C atom alkyl) all as the separate optical antipodes are claimed as new cpds.. Prepn. of Ia/Ib comprises reacting ester deriv. of tryptophan (II) as optical antipode with alkyl valeric acid halide (III) in presence of acid fixing agent to give halogenopentanoyl tryptophan (IV) which is subjected to dehydrating cyclisation with weak base to give hexahydro indoloquinolizinium salt (V) which opt. converted to another salt, is reacted with acrolein in the presence of alkali metal tert. alcoholate catalyst to give hydroxy deshydro E homo eburnane carboxylic acid ester (VII) that is oxidised to give oxo-deshydro-E-homo eburnane carboxylic acid ester (VIII) that is selectively reduced and opt. sepd. into cis and trans isomers of 14-oxo-E-homo eburnane carboxylic acid esters (IXa)/(IXb) followed by hydrolysis to carboxyethyloctahydro indoloquinolizine carboxylic acids (Xa) (Xb) as separate optical antipodes which reacted with mineral oxyhalide and selectively reduced to give Ia and Ib to can be oxidised to give 14-oxo deshydro-E-homo eburnane (XI) as optical antipode. In the formulae R1, R2, R3 are 1-6C alkyl, A is acid residue, X1 and X2 are halo; X3, X4, X5 are acid residue. (Ib) are known cpds. useful as intermediates for preparing cerebral vasodilators, such as vincamine and ethyl (+)-apovincaminate (Cavinton).</p> |
