The first total synthesis of the cytotoxic marine macrolide enigmazole A has been completed in 22 steps (longest linear sequence). The sensitive, densely functionalized 2,4-disubstituted oxazole fragment was constructed using an efficient Negishi-type coupling of an oxazol-2-ylzinc reagent formed directly from the parent ethyl 2-iodooxazole-4-carboxylate by zinc insertion. Other key steps include a hetero-Diels-Alder cycloaddition to form the central embedded pyran ring, a Wittig reaction to unite Eastern and Western hemispheres, and a ring size-selective Keck macrolactonization.

Three new omega-halogenated long-chain 2H-azirines were isolated from the sponge Dysidea fragilis. Their structures revealed heterogeneity in both the composition of the terminal 1,1-dihalo-vinyl group and enantiomeric ratios at C2 of the azirine-2-carboxylate ester terminus. Azirine-2-carboxylate esters were shown to racemize spontaneously. A hypothesis is proposed for the biosynthesis of the azirinecarboxylate family of natural products that involves enzyme-catalyzed free radical halogenation followed by elimination of hydrohalic acid.

Rhizochalins C and D ( 1, 2), new representatives of two-headed glycosphingolipids, were isolated from the sponge Rhizochalina incrustata. Rhizochalin D is an unexpected C 29 homologue of the canonical C 28 dimeric sphingolipid structures. Their structures including absolute configurations were established using spectroscopic data, micromolar-scale Baeyer-Villiger oxidation, and LCMS interpretation of the products. Application of the latter method leads to a revision of the structure of oceanapiside and placement of the keto group at C-18 rather than C-11.