P-35 淡水産渦鞭毛藻Peridinium polonicumの生産する魚毒成分ポロニカムトキシンA、B、Cの構造と合成(ポスター発表の部)
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概要
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Polonicumtoxins A(1), B(2), and C(3), isolated from the freshwater dinoflagellate Peridinium polonicum by Oshima et al. in 1989, exhibit high ichthyotoxic and mouse lethal activities. The probable structures of these natural products were elucidated. However, the availability of only small quantities of these natural products as well as their instability prevented further confirmation of the olefin geometry and detailed investigation of their biological activity. We have completed the syntheses of 1, 2, and 3, and describe here the results. For the formation of a cyclic imine, two methods were applied. One relied on the nucleophilic addition of the appropriate alkyllithium reagent to N-TMS-lactam (6), as developed by Hua et al. While this reaction sequence was successful, the key coupling reaction gave the desired imine (7) only in low yield. We subsequently constructed 7 in a much better yield from keto-azide (15) by triphenylphosphine mediated aza-Wittig cyclization. The key step was a zinc azide mediated Mitsunobu Substitution, and it enabled us to prepare 7 in one-pot from keto-alcohol 14. THP group in 7 was cleaved under mild conditions to afford 3. Esterification of the hydroxy-azide 16 followed by aza-Wittig cyclization successfully yielded compounds 1 and 2. The NMR, MS, and IR data of synthetic 1, 2, and 3 were identical to those of the natural ones, thus unambiguously confirming the assigned structure. The olefin geometry was further confirmed by NOE experiments on the synthetic samples, and all signals on ^<13>C NMR spectra of 1, 2 and 3 were assigned on the basis of ^<13>C decoupled HMQC and HMBC spectra. The ichthyotoxicities of synthesized 1, 2 and 3 were matched those of naturally derived.
- 天然有機化合物討論会の論文
- 1995-09-01