Partial synthesis of harringtonine.

The partial synthesis of harringtonine from cephaltotaxine 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 cephalotaxine in the presence of pyridine to give ester IX. After being treated with hydrichloric-acetic acid, ester IX unerwent Reformatsky reaction to give a mixture (XIV) of harringtonine and its diastereoisomer (epiharringtonine) as the final product which was purified either by countercurrent distribution or column chromatography on neutral alumina. The amounts of the two epimers in the mixture shown by TLC were roughly equal.