83(P69) 新規微小管作用物質WS9885B(ポスター発表の部)

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In the course of screening for novel cell cycle inhibitors, WS9885B(1), C_<24>H_<32>O_5, was isolated from the fermentation broth of Streptomyces sp. No9885. During the NMR measurements, the decomposition of 30% of 1 took place. This instability and ^1H signal overlap made the structure determination difficult. The sample recovered was acetylated to give WB9885B-Ac-1(3) and -2(2). The molecular formula of 2 was established as C_<28>H_<36>O_7, indicating 2 was diacetate of 1. An unprecedented hexacyclic structure was elucidated, but the instability of 2 hindered further structural analysis. In contrast to 1 and 2, 3 was stable in solution. The molecular formula of 3 was determined to be C_<28>H_<36>O_8, one more oxygen than that of 2. The planar structure of 3 was determined by H-H, C-H COSY and HMBC data. The relative configuration of 3 was assumed by a combination of NOE's and vicinal coupling constants as shown in Fig. 4. Finally, X-ray crystallographic analysis of 3 confirmed the structure. In CD_2Cl_2 solution, 2 decomposed gradually and ^1H signals newly generated were superimposable with those of 3. The transformation of 2 to 3 can be explained by epoxidation of the strained double bond. This finding established the structure of 2 and also the structure of 1. The absolute stereochemistry of 1 is now under investigation. WS9885B showed broad antitumor activities in vitro (Table 2) as strong as Taxol and exhibited no antimicrobial activities in vitro (Table 3). WS9885B arrested the cell cycle of HT29 at G2/M phase and promoted assemblies of tublins in vitro. These results showed that WS9885B may have a microtubule-stabilizing activity like Taxol. It is intriguing to note that the stable epoxide 3 is devoid of the antitumor activities.
天然有機化合物討論会の論文
1998-08-31

83(P69) 新規微小管作用物質WS9885B(ポスター発表の部)

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