96(P40) 糸状菌由来の新規プロテアソーム阻害物質TMC-95の単離,構造決定(ポスター発表の部) [in Japanese] 96(P40) Structures of TMC-95, Novel Proteasome Inhibitors from Apiospora montagnei [in Japanese]
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In the course of our screening for proteasome inhibitors, four novel compounds, TMC-95 A〜D (1〜4) have been isolated from the fermentation broth of Arthrinium state of Apiospora montagnei Sacc. TC 1093, isolated from a soil sample. All of the molecular formulas of 1〜4 were established as C_<33>H_<38>N_6O_<10> by high-resolution FAB-MS. The UV and IR spectra of 1〜4 closely resemble to each other. The IR spectra showed absorption bands at 3380-3400, 1720, 1660 and 1515〜4510 cm^<-1> suggesting the presence of the hydroxyl, carbonyl and amide groups. Their structures including the partial absolute stereochemistry were determined by the extensive analyses of 1D and 2D NMR, along with degradation studies. The DQF-COSY and HMBC experiments of 1 revealed the presence of five partial structures (A)〜(E) as shown in Fig. 2. Finally, the key ^1H-^<13>C long range correlations including from four amide protons to corresponding adjacent carbonyl carbons disclosed the connectivity of (A)〜(E), giving us the gloss structures of 1. Comparison of the ^1H and ^<13>C NMR data of 1〜4 revealed the relationships of 1〜4 to be diastereoisomers at C-7 and C-36. The absolute stereochemistry at C-6, 7, 8, 11 and 14 was determined based on the degradation studies by 6N HCl, and NOE analysis along with ^1H-^1H coupling constants. TMC-95A (1) and B (2) strongly inhibited the activity of proteasome.