63 Aphidicolinの生合成とaphidicolane誘導体の生物活性

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Aphidicolin (1) was first isolated as an antiviral antibiotic from Cepharosporium aphidicola and later it has been recognized as a specific inhibitor of DNA-polymerase α. The biosynthetic scheme which includes 9β-8β hydride shift was proposed by Dalziel et al, and later supported by the incorporation experiments with (1,2-^<13>C_2)acetate and (3-^<13>C,4-^2H_2)mevalonate by Bu'Lock et al and Hanson et al (Scheme 1). Effectiveness of ^<13>C^2H_3COONa as a tracer in the terpenoid biosynthesis was tested for aphidicolin. The proton and deuterium decoupled ^<13>C-NMR spectrum of (1) biosynthesized by Nigrospora sacchari in the presence of ^<13>C^2H_3COONa clearly showed ^2H-^<13>C signals in the upfield of corresponding ^1H-^<13>C signals (Fig.2). The presence of β-shifted signal(0.088ppm) at C-9 supported the 1,2-hydride shift which took place in the biosynthesis of (1). The similar analysis of ^1H,^2H-decoupled ^<13>C-NMR spectrum of ergosterol (3) biosynthesized by yeast with ^<13>C^2H_3COONa indicated the presence of β-shifted signals at C-17, 13 and C-24 (Fig.3). These results clearly demonstrated the usefulness of ^<13>C^2H_3COONa in terpenoid biosynthesis, since it gives informations not only on the origin of each carbon atom but also on the 1,2-hydride shifts associated with biosynthesis. The structure of a new aphidicolane (2) isolated from N. sacchari in the course of biosynthetic experiments was established to be 3-deoxy-6β-hydroxyaphidicolin (Fig.4) by X-ray crystallographic analysis. The inhibitory activity of some aphidicolane derivatives (6)-(11) (Fig.5) against Hela DNA-polymerase α is listed in Table 3.
天然有機化合物討論会の論文
1985-09-07

63 Aphidicolinの生合成とaphidicolane誘導体の生物活性

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