Edgar Forche

Biosynthesis of Myxothiazol Z, the Ester-analog of Myxothiazol A in Myxococcus fulvus☆

Abstract Among myxobacteria only strains of Myxococcus fulvus are able to produce in addition to the well known myxothiazol A (1) an analog, myxothiazol Z (2), with an ester-type β-methoxyacrylate pharmacophore. Feeding experiments with labeled precursors established its biosynthesis from the amide (1) presumably via an O-methyl imidate (3).

Isolation, biological activity evaluation, structure elucidation, and total synthesis of eliamid: a novel complex I inhibitor.

Eliamid is a secondary metabolite isolated from two bacterial strains. This molecule features a linear polyketide backbone terminated by a tetramic acid amide moiety. Among other biological activities, eliamid shows a high and specific cytostatic action on human lymphoma and cervix carcinoma cell lines. The 2,4-anti relative configuration of the C-2,C-4-dimethyl substituted amide fragment was assigned by means of Breits rule. The absolute configuration of all stereocenters was determined by a combination of degradation methods, structural similarity analysis and total synthesis. The stereogenic centers were introduced by vinylogous Mukaiyama aldol reaction and two consecutive Myers alkylations. The use of pentafluorophenyl ester as acylation agent allowed the efficient formation of tetramic acid amide. The longest linear sequence in the synthesis consist of 13 steps and proceeds with 12% overall yield. Differential spectroscopy experiments with beef heart submitochondrial particles established that eliamid is a potent inhibitor of the NADH-ubiquinone oxidoreductase complex. Additionally, biosynthesis of eliamid was investigated by feeding experiments with (13)C-labeled precursors.