多様な分枝鎖ポリケタイドの発見

Org. Lett., 2012, 14 (21), pp 5456–5459  /    , DOI: 10.1021/ol302539s ,

Structural Diversity of New C13-Polyketides Produced by Chaetomium mollipilium Cultivated in the Presence of a NAD+-Dependent Histone Deacetylase Inhibitor

Teigo Asai*, Shuntaro Morita, Naoki Shirata, Tohru Taniguchi, Kenji Monde, Hiroaki Sakurai§, Tomoji Ozeki§ and Yoshiteru Oshima*

Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-yama, Aoba-ku, Sendai 980-8578, Japan, Faculty of Advanced Life Science, Frontier Research Center for Post-Genome Science and Technology, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, Japan, §Department of Chemistry and Materials Science, Tokyo Institute of Technology, 2-12-1-H-63 O-okayama, Meguro-ku, Tokyo 152-8551, Japan

Cultivation of Chaetomium mollipilium with nicotinamide, a NAD+-dependent HDAC inhibitor, stimulated its secondary metabolism, leading to the isolation of structurally diverse new C13-polyketides, mollipilin A–E (1–5) as well as two known compounds (6 and 7). Spectroscopic methods, X-ray single crystal diffraction analysis, and VCD elucidated the absolute configurations of structures 1–6, and plausible biosynthetic pathways for 1–7 were proposed based on structural relationships. Mollipilins A (1) and B (2) exhibited moderate growth inhibitory effects on HCT-116 cells.