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Asymmetric Total Synthesis of (+)-Apovincamine and a Formal Synthesis of (+)-Vincamine. Demonstration of a Practical “Asymmetric Linkage” between Aromatic Carboxylic Acids and Chiral Acyclic Substrates

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    Asymmetric Total Synthesis of (+)-Apovincamine and a Formal Synthesis of (+)-Vincamine. Demonstration of a Practical “Asymmetric Linkage” between Aromatic Carboxylic Acids and Chiral Acyclic Substrates
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    Department of Chemistry, Rensselaer Polytechnic Institute, Troy, New York 12180-3590
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    The Journal of Organic Chemistry

    Cite this: J. Org. Chem. 1997, 62, 5, 1223–1229
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    https://doi.org/10.1021/jo961603p
    Published March 7, 1997
    Copyright © 1997 American Chemical Society
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    Abstract

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    Asymmetric syntheses of (+)-apovincamine (1a) and (+)-vincamine (2) are described. Construction of the pentacyclic diene lactam 14, a pivotal intermediate for synthesis of the cis-fused vincane-type alkaloids, began by Birch reduction−alkylation of the chiral benzamide 3 to give the 6-ethyl-1-methoxy-4-methyl-1,4-cyclohexadiene 4. Conversion of 4 to 2,5-cyclohexadienone 5 (92% overall yield from 3) and HPLC analysis of 5 demonstrated the diastereomeric purity resulting from the Birch reduction−alkylation to be >100:1. Dienone 5 was converted to butyrolactone 9 (47% overall yield from 3), and 9 was coupled with tryptamine (10) to give the amide 11a. Amido keto aldehyde 13 was obtained from 11a, and acid-catalyzed tricyclization and subsequent base-induced elimination of MeOH provided the desired cis-fused pentacyclic diene lactam 14. Examination of the two-step process 13 → 14 revealed a novel base-induced epimerization at C(21) which served to interconvert 14 and 17, possibly by the involvement of a homoenolate. Diene lactam 14 was converted to (+)-apovincaminal 20a, an intermediate in the synthesis of (+)-apovincamine (1a) reported by Winterfeldt and co-workers. A new procedure for conversion of 20a to 1a involves conversion of 20a to the acetal 20b and treatment of 20b with NBS/AIBN in CCl4. The conversion of 1a to vincamine (2) has been reported by Oppolzer and co-workers.

    Copyright © 1997 American Chemical Society

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     Abstract published in Advance ACS Abstracts, February 1, 1997.

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    38. A. G. SCHULTZ, W. P. MALACHOWSKI, Y. PAN. ChemInform Abstract: Asymmetric Total Synthesis of (+)‐Apovincamine and a Formal Synthesis of (+)‐Vincamine. Demonstration of a Practical “Asymmetric Linkage” Between Aromatic Carboxylic Acids and Chiral Acyclic Substrates.. ChemInform 1997, 28 (30) https://doi.org/10.1002/chin.199730200
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    The Journal of Organic Chemistry

    Cite this: J. Org. Chem. 1997, 62, 5, 1223–1229
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jo961603p
    Published March 7, 1997
    Copyright © 1997 American Chemical Society
    Request reuse permissions

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