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A Flexible Asymmetric Approach to Methyl 5-Alkyltetramates and Its Application in the Synthesis of Cytotoxic Marine Natural Product Belamide A

Authors

  • Dr. Hong-Qiao Lan,

    1. Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (P.R. China), Fax: (+86) 592-2186400
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  • Dr. Jian-Liang Ye,

    1. Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (P.R. China), Fax: (+86) 592-2186400
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  • Dr. Ai-E Wang,

    1. Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (P.R. China), Fax: (+86) 592-2186400
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  • Prof. Yuan-Ping Ruan,

    1. Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (P.R. China), Fax: (+86) 592-2186400
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  • Prof. Dr. Pei-Qiang Huang

    Corresponding author
    1. Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (P.R. China), Fax: (+86) 592-2186400
    2. State Key Laboratory of Bioorganic and Natural Products Chemistry, 354 Fenglin Lu, Shanghai 200032 (P. R. China)
    • Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (P.R. China), Fax: (+86) 592-2186400
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Abstract

By using a methyl tetramate derivative (R)- or (S)-9 as a novel chiral building block, a direct, flexible, and highly enantioselective approach to methyl (R)- or (S)-5-alkyltetramates (2) is disclosed. Among the synthesized methyl 5-alkyltetramates 2, methyl 5-methyltetramate (2 a) is found in cytotoxic mirabimide E (4) and dysideapyrrolidone (5), and methyl 5-benzyltetramate (2 g) is a substructure in the potent antineoplastic dolastatin 15 (3). On the basis of this method, the first asymmetric synthesis of the antimitotic tetrapeptide belamide A (7) has been achieved in seven steps from (S)-9, with an overall yield of 23.8 %. Not only have the structure and absolute configuration of (+)-belamide A (7) been confirmed, but also the solvent used for recording the 13C NMR spectrum, the 13C NMR spectrum data correlation, and optical rotation data of natural belamide A (7) have been revised.

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