The total synthesis of biosynthetically related monoterpene indole alkaloids

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Abstract

Total syntheses of the biosynthetically- related monoterpene indole alkaloids, (-)- rhazinilam, (-)- rhazinicine, (-)- mersicarpine, leuconodine B, melodinine E, and leuconoxine are described. Total synthesis of (-)- rhazinilam was achieved by each of two strategies; 1) regioselective 1,3- dipolar cycloaddition of an optically active münchnone intermediate prepared from D- aspartic acid dimethyl ester; 2) construction of the indolizinone core by a gold- catalyzed double cyclization cascade. The second generation synthetic route was also applied to the first asymmetric total synthesis of (-)- rhazinicine. In addition, the intramolecular gold- catalyzed double cyclization cascade was extended to a novel synthesis of substituted pyrroles, in which gold catalysts behaved as an auto- tandem catalyst, and played a dual role in activating terminal acetylenes both by forming gold acetylides and by π - coordination. A concise total synthesis of (-)- mersicarpine was achieved by an six- pot/nine- step sequence in 21% overall yield from commercially available 2- ethylcyclohexanone. An azepino[3,2- b]indole intermediate was synthesized via d'Angelo's asymmetric Michael addition, Fischer indole synthesis, and DIBALH- mediated reductive ring- expansion reaction. Finally, divergent total syntheses of leuconodine B, melodinine E, and leuconoxine were achieved. The crucial formation of the key [5.5.6.6]diazafenestrane intermediate was accomplished by oxidative cyclic aminal formation and regioselective ring- closing metathesis.

Original languageEnglish
Pages (from-to)1120-1129
Number of pages10
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume73
Issue number11
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Organic Chemistry

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