Department of Chemistry, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka, 558-8585, Japan.
Japan Food Research Laboratories, Ibaraki-shi, Osaka, 567-0085, Japan.
Chemistry. 2017 Jul 18;23(40):9535-9545. doi: 10.1002/chem.201701475. Epub 2017 Jun 9.
The enantioselective total syntheses of lepadiformine marine alkaloids, azatricyclic natural products isolated from marine tunicates, were completed. These alkaloids have a unique chemical structure characterized by the trans-1-azadecalin (AB ring system) fused with the spirocyclic ring (AC ring system). Here we found that a cycloisomerization reaction from functionalized linear substrates to a 1-azaspiro[4.5]decane framework corresponding to the AC ring in lepadiformines is promoted by a catalytic amount of mercury(II) triflate (Hg(OTf) ). The total syntheses of (-)-lepadiformines A and B were achieved in 28 % and 21 % overall yields, respectively, through the novel cycloisomerization reaction. The syntheses of (+)- and (-)-lepadiformine C hydrochloride salts also enabled us to determine the absolute configuration of natural lepadiformine C. It has been found that a phenomenon of enantiodivergence occurs in lepadiformine alkaloids from a single species of marine tunicate, Clavelina moluccensis. The cytotoxic activities of synthesized lepadiformine hydrochloride salts and their synthetic intermediates were evaluated.
已完成海洋被囊动物来源的非对映选择性全合成脂蟾肽海洋生物碱，这类生物碱具有独特的化学结构，特征为反-1-氮杂双环[4.5]癸烷（AB 环系统）与螺环（AC 环系统）稠合。在此，我们发现功能化线性底物经汞(II)三氟甲磺酸酯（Hg(OTf) ）催化的环异构化反应可得到脂蟾肽骨架的 1-氮杂螺[4.5]癸烷（AC 环）。通过新颖的环异构化反应，(-)-脂蟾肽 A 和 B 的总收率分别达到 28%和 21%。(+)-和(-)-脂蟾肽 C 盐酸盐的合成也使我们能够确定天然脂蟾肽 C 的绝对构型。从单一海洋被囊动物 Clavelina moluccensis 中发现脂蟾肽生物碱存在对映体发散现象。评估了合成的脂蟾肽盐酸盐及其合成中间体的细胞毒性活性。
