Structures of TMC-95A−D:  Novel Proteasome Inhibitors from Apiospora m ontagnei Sacc. TC 1093

• Published in: Journal of organic chemistry 2000-02, Vol.65 (4), p.990-995
• Main Authors: Kohno, Jun, Koguchi, Yutaka, Nishio, Maki, Nakao, Kazuya, Kuroda, Masataka, Shimizu, Ryo, Ohnuki, Tetsuo, Komatsubara, Saburo
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo991375+

Four novel proteasome inhibitors, TMC-95A−D (1−4) have been isolated from the fermentation broth of Apiospora montagnei Sacc. TC 1093, isolated from a soil sample. All of the molecular formulas of 1−4 were established as C33H38N6O10 by high-resolution FAB-MS. Their planar structures were determined on the basis of extensive analyses of 1D and 2D NMR, and degradation studies. Compounds 1−4 have the same planar structures to each other, and are unique highly modified cyclic peptides containing l-tyrosine, l-aspargine, highly oxidized l-tryptophan, (Z)-1-propenylamine, and 3-methyl-2-oxopentanoic acid units. The absolute configuration at C-11 and C-36 of 1−4 was determined based on chiral TLC and HPLC analyses of their chemical degradation products. The ROESY analysis along with 1H−1H coupling constants clarified the absolute stereochemistry at C-6, -7, -8, and -14 of the cyclic moieties. These studies revealed the relationships of 1−4 to be diastereomers at C-7 and C-36.