The revised structure, total synthesis, and absolute configuration of streptophenazine A.

A total synthesis of both diastereomers of the originally proposed structure for streptophenazine A (1) has been achieved. However, both synthetic compounds are different from the natural product. Re-examination of NMR data reported for streptophenazine A and a concise total synthesis of both diastereomers of 17 (17a and 17b) led to the structural revision of streptophenazine A to 17b. Asymmetric synthesis of (-)-streptophenazine A was also conducted, and its absolute configuration was determined to be 1'S,2'R.

CT2108A and B: New fatty acid synthase inhibitors as antifungal agents.

A systematic screen for new natural products that displayed antifungal activity by inhibition of fungal fatty acid synthase (FAS) led to the discovery of two new fungal metabolites, designated CT2108A (1) and CT2108B (2). The metabolites were produced by Penicillium solitum (Westling) strain CT2108 and were classified as azaphilones. The structures of these new metabolites were determined using a variety of 1D and 2D NMR experiments, including COSY, HMQC, and HMBC. The chemical conversion of CT2108A to CT2108B was effected using WCl(6). The related metabolite, patulodin (3), was also isolated from the fermentation culture of this P. solitum isolate. Both new compounds inhibited fungal FAS, and neither was found to significantly inhibit human FAS activity.

Biotransformations of the cardiovascular drugs mexrenone and canrenone.

Microbial transformation studies of the cardiovascular drugs mexrenone (1) and canrenone (2) were conducted. Thirty-nine biotransformations of mexrenone and 84 biotransformations of canrenone were analyzed. Metabolism of the substrate was observed in the majority of these cases. Several monohydroxylated derivatives were detected by HPLC-MS-UV and subsequently identified. Two new mexrenone derivatives, 11alpha- (3) and 12beta-hydroxymexrenone (4), and the known metabolite 6beta-hydroxymexrenone (5) were isolated as major products produced by the Beauveria bassiana ATCC 13144 bioconversion (3) and the Mortierella isabellina bioconversion (4 and 5), respectively. Single-elimination products were also sought; however, only the production of the known metabolite Delta(1,2)-mexrenone (6) by several bacteria was confirmed. One new monohydroxylated derivative of canrenone, 9alpha-hydroxycanrenone (7), was isolated as a major product from the Corynespora cassiicola bioconversion. Structure elucidation of all metabolites was based on NMR and HRMS analyses.

R176502, a new bafilolide metabolite with potent antiproliferative activity from a novel Micromonospora species.

During the course of a screening program intended to identify new antiproliferative agents, a new bafilolide metabolite was discovered. R176502 (1) was isolated from the liquid fermentation cultures of a novel Micromonospora species found in African river bottom sediment. It was purified from ethyl acetate extracts using a series of countercurrent chromatographic steps. The structure was determined using 1- and 2-D NMR experiments. Three previously described bafilomycins (bafilomycins A1 (2), B1 (3), and B2 (4)) were also isolated (from other microbial strains). R176502 exhibited potency for inhibition of tumor cell proliferation in the nM range of concentrations.

Phomacins: Three Novel Antitumor Cytochalasan Constituents Produced by a Phoma sp.

Three novel cytochalasans, phomacins A, B and C, were isolated from a fermentation broth of the fungus Phoma sp. and purified by HSCCC (high speed countercurrent chromatography) followed by HPLC. The structures were determined by 1D and 2D NMR techniques. All three compounds have shown potent inhibitory activity against the HT29 colonic adenocarcinoma cell line.