APPLICATION OF RADICAL CYCLISATION/IODINE ATOM-TRANSFER TO THE CHIRAL SYNTHESIS OF (-)-METHYLENOLACTOCIN

Methylenolactocin, an antitumour antibiotic, has been synthesised through an efficient radical cyclisation process on a chiral iodo acetylenic ester, Chiral iodohydrins may be formed by regioselective opening of a chiral epoxy ester, prepared by Sharpless epoxidation. C-2 opening is achieved with TMSCl-NaI and C-3 attack with MgI2. Subsequent esterification of the 2-iodo compound by reaction with substituted propynoyl triflates gives the key iodo acetylenic esters. This route is highly adaptable to the synthesis of analogues.