20 微生物の生産する新規キチン合成酵素阻害剤Guanofosfocin類の単離と構造決定(口頭発表の部)

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In our screening program for chitin synthase(CHS) inhibitor, we isolated novel nucleotide inhibitors, guanofosfocin A (1), produced by a Streptmyces sp., and guanofosfocins B (2) and C (3), produced by Trichoderma sp. Though it was very difficult to isolate the pure compound without degradation, because of its instability, we could isolate and determine their structures utilizing the radical scavenger, n-propyl gallate, during the isolation and the NMR experiments to prevent the degradation. We isolated 50mg of 1, 164mg of 2 and 15mg of 3 from each broth filtrate using a series of column chromatography. The molecular formula(C_<17>H_<25>N_5O_<17>P_2) of 1 was determined based on HRFAB-MS, ^1H-NMR^<13>C NMR and ^<31>P NMR spectra data. The characteristic UV absorption of 1 suggested the presence of purine base moiety like guanine. We detremined the structure of 1, except for the base moiety and the cyclic linkage, from the analysis of the ^1H, ^<13>C, ^<31>P NMR, HMBC, HOHAHA and selective COSY experiments. The presence of a D-mannose and 8-hydroxyguanocine substructure was comfirmed by the comparison with the authentic sample and the cyclic linkage between the two was determined by 2D NMR experiments and by comparing NMR and UV spectra of 1 with those of related compound. The structure of 2 (C_<16>H_<23>N_5O_<17>P_2)was identified as demethyl derivative of 1 with comparing UV, ^1H, ^<13>C, ^<31>P NMR and we determined the structure of 3 (C_<29>H_<43>N_9O_<26>P_2) based on the amino acid analysis, UV,^1H,^<13>C,^<31>P NMR, HMBC, pH shift experiments of ^<13>C NMR. The absolute configuration at the acetal position of 1 was suggested to be [s] by the NOESY experiments and interatomic distanse of S and R isomers calculated by molecular dynamics calculation(NEMESIS). Guanofosfosins A, B and C show potent inhibitory activity against Candida albicans CHS 2 with 0.025, 0.026 and 0.008μM, respectively.
天然有機化合物討論会の論文
1996-09-02

20 微生物の生産する新規キチン合成酵素阻害剤Guanofosfocin類の単離と構造決定(口頭発表の部)

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