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Asymmetric Synthesis of the β-Methyl-Substituted Analogues of (+)-Tanikolide and (–)-Malyngolide

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Asymmetric Synthesis of Bioactive Lactones and the Development of a Catalytic Asymmetric Synthesis of α-Aryl Ketones

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Abstract

The asymmetric synthesis of all 4 diastereomers of β-methyl analogues of the marine natural products (+)-tanikolide, which displays antifungal activity, and (−)-malyngolide, which displays antimicrobial activity, has been successfully carried out. The final two diastereomers were synthesised in this Ph.D. project in a 9-step synthesis in 24.9 and 10.8 % overall yields, respectively. Key steps in the synthetic route included Sharpless asymmetric epoxidation and ZrCl4-catalysed intramolecular acetalisation as the key steps. The β-methyl substituted analogues were designed to probe the effect the β-methyl group would have on the bioactivity of these compounds. The biological testing of these compounds revealed that none of these analogues showed any antifungal activity however, one of the analogues of malyngolide showed promising activity against MRSA with an MIC of 12.5 μg/mL.

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  1. Department of Chemistry, Imperial College London, London, UK

    Robert Doran

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  1. Robert Doran
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Doran, R. (2015). Asymmetric Synthesis of the β-Methyl-Substituted Analogues of (+)-Tanikolide and (–)-Malyngolide. In: Asymmetric Synthesis of Bioactive Lactones and the Development of a Catalytic Asymmetric Synthesis of α-Aryl Ketones. Springer Theses. Springer, Cham. https://doi.org/10.1007/978-3-319-20544-1_2

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