著者

錦部 健人 鴇田 百栄 滝 直人 西川 慶祐 森本 善樹

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

vol.59, pp.195-200, 2017

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In the past, through enantioselective total synthesis, our laboratory has found that isodehydrothyrsiferol (5), a marine squalene-derived triterpene polyether isolated from the red alga <I>Laurencia viridis</I>, shows partial enantiodivergency in that six asymmetric centers in the ABC ring system (a dioxabicyclo[4.4.0]decane ring system with an attached bromine-containing tetrahydropyranyl ring that forms the core structure of the triterpene polyethers produced from the genus <I>Laurencia</I>) are enantiomeric to those of other members of the thyrsiferol family.<SUP>1)</SUP> In this presentation, our laboratory performed the total syntheis of aplysiol B and 22-hydroxy-15(28)-dehydrovenustatriol whose absolute configurations have never been determined to research the partial enantiodivergency in the thyrsiferol family in depth.Aplysiol B, a member of the thyrsiferol family isolated from the sea hare <I>Aplysia dactylomela</I>, possesses feeding-deterrent and ichthyotoxic properties. However, the proposed structures 6a<SUP>2)</SUP> and 6b<SUP>3)</SUP> were in contradiction to the biogenetic hypothesis. Therefore, we reconsidered the biogenetic pathway of aplysiol B and synthesized the reasonable structure 6c through a key Shi epoxidation<SUP>12)</SUP> followed by a 5-<I>exo</I> cyclization and a subsequent 6-<I>endo</I> bromoetherification using BDSB.<SUP>13)</SUP> The spectral data and the optical rotation of synthetic 6c were in agreement with those reported for the natural sample.<SUP>2)</SUP> As a result, the first total synthesis of aplysiol B was accomplished, and the reported structures 6a and 6b were revised to 6c.The planar structure of 22-hydroxy-15(28)-dehydrovenuatatriol was determined by NMR analysis.<SUP>6)</SUP> The stereostructure of the ABC ring system was elucidated by comparing the NMR data with those of dehydrothyrsiferol (4), whose absolute structure was known. However, the stereochemical relationship between the ABC ring system and D ring due to the intervening methylene chain and the absolute configuration has not been determined to date. Our laboratory synthesized the proposed structure 8a <I>via</I> a key Suzuki-Miyaura cross-coupling between the BC ring system 19 and D ring 20. However, the NMR spectra of synthetic 8a did not match with those of the reported data.<SUP>6)</SUP> We also synthesized 8b, a possible diastereomer of 8a, and the proposed structure 8a was revised to 8b. Moreover, we observed that the ABC ring system of 8b has the same absolute configuration as that of isodehydrothyrsiferol (5).Considering an enantiodivergent phenomenon in the common skeleton of the thyrsiferol family, based on the biogenesis of the squalene-derived thyrsiferol family suggested by the Fernández group,<SUP>4)</SUP> we propose the biogenesis of 6c and 8b <I>via</I> the bromocation-initiated epoxide-opening cascade reaction of squalene pentaepoxide 37.