PARTIAL SYNTHESIS OF HARRINGTONINE
摘要
The partial synthesis of harringtonine from cephalotaxine has been described. A key intermediate, 5, 5-dimethyl-2-hydroxytetrahydrofuran-2-carboxylic acid (Ⅴ), prepared from 4-methyl-1, 4-valerolactone, was dehydrated smoothly to give 5, 5-dihydrofuran-2-carboxylic acid (Ⅵ). Through its sodium salt, Ⅵ was converted into the corresponding acyl chloride Ⅷ. which reacted with cophalotaxine in the presence of pyridine to give ester Ⅸ. After being treated width hydrichloric-acetic acid, ester Ⅸ underwent Reformatsky reaction to give a mixture (ⅩⅣ)of harringtonine and its diastereoisomer (epiharringtonine) as the final product which was purified either by countereurrent distribution or column chromatography on neutral alumina. The amounts of the two epimers in the mixture shown by TLC were roughly equal.