Enantioselective synthesis of the larger fragment of pamamycin-607

The enantiomerically pure methyl ester of the complete larger hydroxy acid (C(1)C(18)) of the macrodiolide antibiotic pamamycin-607 has been synthesized using a general sultone route to actic acids and analogs. The requisite N,N-dimethylamino moiety was introduced by Mitsunobu inversion with hydrazoic acid followed by a reaction cascade involving hydrogenation and double reductive methylation.