96(P16) 強力な鎮痛作用を有するダフナンジテルペン、レジニフェラトキシンのエナンチオ選択的全合成(ポスター発表の部)
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概要
- 論文の詳細を見る
Resiniferatoxin (RTX, 1), a structurally unique daphnane-type diterpene, was identified in the latex of three species of Euphobia (E. resinifera, E. poissonii, and E. unispina) on the basis of its extraordinary irritant activity. Structurally, RTX is similar to phorbol-related diterpenes. Unlike the most active phorbol myristate acetate (2) however, RTX is not a tumor promoter and does not compete for the phorbol ester binding site on protein kinase C. RTX also displays structural similarity to capsaicin (3), the major active constituent of common red pepper showing potent irritant and nociceptive properties. Indeed, RTX acts as a superpotent capsaicin analog and displays 10^3 to 10^5 times greater potency than 3 for many of these biological responses. Herein we detail a convergent and enantioselective synthesis of tricycle 6, a general precursor to the daphnanes, and the first total synthesis of RTX, using 6. The synthesis of tricycle 6 has been achieved through a 21-step sequence in 9% overall yield. The key strategy employed in this approach involves: (i) an intramolecular [5C+2C] oxidopyrilium-alkene cycloaddition for BC-ring annulation and (ii) a zirconocene promoted cyclization for A-ring annulation. This synthetic strategy should permit the practical and reliable construction of the daphnanes and a variety of analogs. Completion of the synthesis of RTX required: (i) installation of the quaternary center at C13; (ii) B-ring modification; (iii) phenylacetyl orthoester formation; (iv) A-ring modification; and (v) attachment of the C20 homovanillyl side chain. The seven stereogenic centers were synthesized in a highly controlled manner. Thus the first synthesis of RTX, identical in all respects to the natural material, has been achieved in 23 steps from tricycle 6.
- 天然有機化合物討論会の論文
- 1996-09-02
著者
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WENDER Paul
スタンフォード大・化学
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Wender Paul
スタンフォード大
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田村 典一
武田薬品工業(株)
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中平 博之
住友製薬(株)
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上野 能秀
住友製薬(株)
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Jesudason Cynthia
スタンフォード大
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