Abstract

The synthesis of seco acid 41 of the macrolactone part of 15-epi-exiguolide, containing a bis-pyran subunit and a trans double bond, is described. Key features of the synthetic strategy include a Feringa–Minnaard asymmetric organocuprate addition to unsaturated ester 17 to set the stereocenter at C15. The derived acid 8 (C9–C16 fragment) was ideally suited for combination with aldehyde 9 (C17–C21 fragment) via an aldol strategy leading to β-lactone 25 which upon thermal decarboxylation provided alkene 26. Chain extension led to propargylic alcohol 7. Treatment of 7 with a LAu⁺ catalyst promoted a Meyer–Schuster rearrangement to enone 30 that led to cis-tetrahydropyran 31 via intramolecular oxa-Michael reaction. The second pyran ring was prepared from alkoxy ketone 5 by reductive cyclization. The further steps toward macrolactone 43 were hampered by the epimeric mixture at C5.

The synthesis of seco acid 41 of the macrolactone part of 15-epi-exiguolide, containing a bis-pyran subunit and a trans double bond, is described. Key features of the synthetic strategy include a Feringa–Minnaard asymmetric organocuprate addition to unsaturated ester 17 to set the stereocenter at C15. The derived acid 8 (C9–C16 fragment) was ideally suited for combination with aldehyde 9 (C17–C21 fragment) via an aldol strategy leading to β-lactone 25 which upon thermal decarboxylation provided alkene 26. Chain extension led to propargylic alcohol 7. Treatment of 7 with a LAu⁺ catalyst promoted a Meyer–Schuster rearrangement to enone 30 that led to cis-tetrahydropyran 31 via intramolecular oxa-Michael reaction. The second pyran ring was prepared from alkoxy ketone 5 by reductive cyclization. The further steps toward macrolactone 43 were hampered by the epimeric mixture at C5.

中文翻译：

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15-表-Exiguolide核心结构的探讨。

摘要

描述了包含双-吡喃亚基和反式双键的15-表-exiguolide大内酯部分的癸二酸41的合成。合成策略的关键特征包括在不饱和酯17中添加Feringa-Minnaard不对称有机铜酸酯，以将立体中心设定在C15。衍生的酸8（C9–C16片段）非常适合与醛9（C17–C21片段）通过醛醇缩合策略形成β-内酯25结合，后者在热脱羧后可提供烯烃26。扩链导致炔丙醇7。LAu治疗7⁺催化剂促进了Meyer-Schuster重排至烯酮30，通过分子内的oxa-Michael反应导致了顺式四氢吡喃31。第二吡喃环通过还原环化由烷氧基酮5制备。朝向大内酯43的进一步步骤受到C5的差向异构体混合物的阻碍。

描述了包含双-吡喃亚基和反式双键的15-表-exiguolide大内酯部分的癸二酸41的合成。合成策略的关键特征包括在不饱和酯17中添加Feringa-Minnaard不对称有机铜酸酯，以将立体中心设定在C15。衍生的酸8（C9–C16片段）非常适合与醛9（C17–C21片段）通过醛醇缩合策略形成β-内酯25结合，后者在热脱羧后可提供烯烃26。扩链导致炔丙醇7。LAu治疗7⁺催化剂促进了Meyer-Schuster重排至烯酮30，通过分子内的oxa-Michael反应导致了顺式四氢吡喃31。第二吡喃环通过还原环化由烷氧基酮5制备。朝向大内酯43的进一步步骤受到C5的差向异构体混合物的阻碍。