51(P11) 糸状菌の生産する新規protein farnesyltransferase阻害剤andrastin類に関する研究(ポスター発表の部)

概要

論文の詳細を見る
During our screening for protein farnesyltransferase (PFTase) inhibitors of microbial origin, we have found new compounds, andrastins A〜D (1〜4), from the cultured broth of Penicillium sp. FO-3929. The compounds 1〜4 were purified from EtOAc extracts by silica gel chromatography, ODS chromatography and HPLC. The molecular formulae of 1〜4 were elucidated by HR-FAB-MS to be C_<28>H_<38>O_7, C_<28>H_<40>O_7 C_<28>H_<40>O_6, and C_<26>H_<36>O_5, respectively. The structures of 1〜4 were elucidated by various NMR experiments. As 1〜4 had a ketoenol tautomer that made difficult to elucidate the structure, 2D-INADEQUATE experiments and ^<13>C-^<13>C decoupling experiments using ^<13>C-labeled 1 were carried out. The structure of 2〜4 were elucidated by NMR experiments comparing that of 1. The absolute configuration of a p-bromobenzoyl derivative of 1 was elucidated by X-ray crystallography. The X-ray crystallography was revealed that 1 has an ent-5α,14β-androstan skeleton. The configuration of 1 coincided with its NOE experiments. The biosynthetic studies of andrastins also employed ^<13>C-labeled 1. The results of ^<13>C-NMR spectra of 1 labeled with [2-^<13>C] acetate and [1,2-^<13>C] acetate suggested that andrastins were meroterpenoide that were synthesized from a farnesyl pyrophosphate and a tetraketide. The IC_<50> values of 1〜4 against protein farnesyltransferase from human THP-1 cells were 24.9, 47.1, 13.3, and 25.7μM, respectively.
天然有機化合物討論会の論文
1996-09-02

51(P11) 糸状菌の生産する新規protein farnesyltransferase阻害剤andrastin類に関する研究(ポスター発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク