myxothiazol and oudemansin

This review summarizes the chemoenzymatic synthesis of the biologically active natural products based on a combination of chemical diastereoselectivity and enzymatic enantioselectivity using biocatalyst. Asymmetric reduction of 2-methyl-3-keto ester with yeast gave the optically active syn-2-methyl-3-hydroxy ester, which was converted to natural product such as (-)-oudemansin B. Asymmetric hydrolysis of 3-acetoxy-2-methy esters possessing syn- or anti-structure afforded the optically active 3-hydroxy-2-methyl esters and 3-acetoxy-2-methy esters corresponding to the starting material. One of these optically active 3-hydroxy-2-methyl esters was converted to aglycone of macrolide, venturicidins A and B possessing 10 chiral centers. Both primary alcohols possessing a chiral center at β-position of hydroxyl group and secondary alcohols were subjected to the lipase-assisted acylation in the presence of acyl donor to afford the optically active esters and the optically active alcohols corresponding to the starting material. These optically active compounds were converted to the biologically active natural products such as bisabolane type sesquiterpenes, decaline type diterpenes or triterpenes, nikkomycin B, (+)-asperlin, (-)-chuangxinmycin, (-)-indolmycin, cystothiazoles melithiazols, myxothiazols and piericidins possessing antifungal and cytotoxicic activities, inhibition of NADH oxidation, etc. Reaction of primary alcohol and glucose using immobilized β-glucosidase gave alkyl β-glucosides in high yield. Pentaacetate of allyl β-glucoside was subjected to Mizoroki-Heck type reaction with phenylboronic acid derivatives to give phenylpropenoid β-D-glucopyranosid congeners.

Topics: Acrylates; Biological Products; Biotransformation; Dipeptides; Enzymes; Indoles; Methacrylates; Nucleosides; Pyridines; Stereoisomerism; Thiazoles

Topics: Acrylates; Animals; Antifungal Agents; Fatty Acids, Unsaturated; Humans; Methacrylates; Strobilurins; Thiazoles

New antibiotic compounds, melithiazols, were isolated from the culture broth of strains of the myxobacteria Melittangium lichenicola, Archangium gephyra, and Myxococcus stipitatus. The compounds belong to the group of beta-methoxyacrylate (MOA) inhibitors and are related to the myxothiazols. The melithiazols show high antifungal activity, but are less toxic than myxothiazol A and its methyl ester in a growth inhibition assay with mouse cell cultures. The melithiazols inhibit NADH oxidation by submitochondrial particles from beef heart. Melithiazol A blocks the electron transport within the bc1-segment (complex III) and causes a red shift in the reduced spectrum of cytochrome b.

Topics: Acrylates; Animals; Antifungal Agents; Cell Respiration; Cytochrome b Group; Drug Evaluation, Preclinical; Energy Metabolism; Fatty Acids, Unsaturated; Fermentation; Humans; Infant; Inhibitory Concentration 50; Methacrylates; Mice; Microbial Sensitivity Tests; Mitochondria, Heart; Myxococcales; NAD; Strobilurins; Structure-Activity Relationship; Thiazoles

Topics: Acrylates; Alkenes; Animals; Antifungal Agents; Antimycin A; Cattle; Cytochrome b Group; Cytochromes; Cytochromes c1; Electron Transport; Fatty Acids, Unsaturated; Methacrylates; Spectrum Analysis; Strobilurins; Structure-Activity Relationship; Submitochondrial Particles; Thiazoles; Valerates