A total synthesis of spirastrellolide A methyl ester.

A concise total synthesis of spirastrellolide A methyl ester (1 a, R(1) =Me) as the parent compound of a series of highly cytotoxic marine macrolides is disclosed, which exploits and expands the flexibility of a synthesis plan previously developed by our group en route to the sister compound spirastrellolide F methyl ester (6 a, R(1) =Me). Key to success was the masking of the signature Δ(15,16) -bond of 1 a as a C16-carbonyl group until after the stereogenic center at C24 had been properly set by a highly selective hydrogenation of the C24 exo-methylene precursor 66. Conformational control over the macrocyclic frame allowed the proper stereochemical course to be dialed into this reduction process.

Total synthesis of a noricumazole A library and evaluation of HCV inhibition.

The total synthesis of 16 new ion channel inhibitors derived from noricumazole A, a secondary metabolite from the myxobacterium Sorangium cellulosum, is reported. Particular focus of library design is put on stereochemical permutations in the central region (C9 and C11), the oxazole moiety and the side chain at C4 of the isochromanone moiety. Noricumazole A and all new noricumazole derivatives were tested in an assay system with inhibitory effect on the hepatitis C virus (HCV) life cycle.