SYNTHESIS OF 18-O-METHYL MYCALAMIDE-B

Metallated dihydropyran 9 and the dihydropyranone 10 previously used i n a synthesis of the insect toxin pederin were adapted to the synthesi s of 18-O-methyl mycalamide B, the most potent derivative of the anti- tumour agents isolated from a sponge, Key steps in the synthesis inclu de the oxidation of enol silane 11 from the more hindered face using d imethyldioxirane to introduce the hydroxy group at C-12 and the acylat ion of 6-lithio-3,4-dihydro-2N-pyran 9 with oxalamide 8 to forge the N -(1-alkoxy-1-alkyl)amide bridge. Biological tests in human tumour cell lines confirm the potent anti-proliferative effect of 18-O-methyl myc alamide B in pM concentrations.