40 新規フォスフォリパーゼC阻害物質Hispidospermidinの構造決定(口頭発表の部)

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In our screening program for new phospholipase C (PLC) inhibitors of microbial origin, we discovered a novel PLC inhibitor hispidospermidin (1) from the culture broth of Chaetosphaeronema hispidulum (Cda) Moesz NR7127. Hispidospermidin (1) was isolated by Amberlite IRC-50 and Diaion HP-21 column chromatography and solvent extraction. The molecular formula was determined to be C_<25>H_<47>N_3O by HREI-MS and NMR spectral data. Its structure was elucidated as a cage compound with a trimethylspermidine side chain based on various 2D NMR studies. The trans relation between 8a-H and C-10 was established from the coupling constant ^3J C10-H8a=5Hz obtained by the J C-H resolved 2D spectroscopy. The cis relations between 6-CH_3 and 10-Hβ and between 11-H and 3-CH_3 were determined by the NOE experiments on 1. The absolute configuration of 1 was elucidated by the modified Mosher's method on the (R)- and (S)-MTPA amides of a derivative (4) of 1. 1 inhibits rat brain PLC with an IC_<50> of 16μM, whereas the primary amine 4 does not at concentrations up to 7.4mM. Since spermine (IC_<50>=59μM) and spermidine (IC_<50>=1.2mM) also inhibit the PLC weakly, it is suggestive that the polyamine moiety in 1 is essential for the inhibitory activity, and the hydrophobic substituents in 1 potentiate the inhibitory activity.
天然有機化合物討論会の論文
1993-09-10