Oudemansin A

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.

Valuable natural compounds produced by a variety of microorganisms can be used as lead molecules for development of new agrochemicals. Furthermore, high-throughput in vitro screening systems with specific modes of action can increase the probability of discovery of new fungicides. In the current study, a rapid assay tested with various microbes was developed to determine the degree of respiratory inhibition of Saccharomyces cerevisiae in two different liquid media, YG (containing a fermentable carbon source) and NFYG (containing a non-fermentable carbon source). Based on this system, we screened 100 fungal isolates that were classified into basidiomycetes, to find microbial secondary metabolites that act as respiratory inhibitors. Consequently, of the 100 fungal species tested, the culture broth of an IUM04881 isolate inhibited growth of S. cerevisiae in NFYG medium, but not in YG medium. The result is comparable to that from treatment with kresoxim-methyl used as a control, suggesting that the culture broth of IUM04881 isolate might contain active compounds showing the inhibition activity for respiratory chain. Based on the assay developed in this study and spectroscopic analysis, we isolated and identified an antifungal compound (-)-oudemansin A from culture broth of IUM04881 that is identified as Oudemansiella venosolamellata. This is the first report that (-)-oudemansin A is identified from O. venosolamellata in Korea. Taken together, the development of this assay will accelerate efforts to find and identify natural respiratory inhibitors from various microbes.

The first synthesis of 9-methoxystrobilurin-type beta-substituted MOAs was successfully achieved. A chiral oudemansin-type beta-substituted MOA was also synthesized utilizing Mukaiyama's asymmetric aldol reaction. Antifungal activities of the synthesized compounds against several representative fungi were examined by disk-diffusion assay. As a result, unique and superior antifungal properties of 9-methoxystrobilurin-type beta-substituted MOAs compared with those of oudemansin-type analogue were clearly revealed.