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Synlett 2023; 34(17): 2017-2021
DOI: 10.1055/a-2099-6389
letter

Synthetic Studies toward the C1–C12 Fragment of Amphidinolide U

Ismaila Ciss
a   BioCIS, Université Paris-Saclay, CNRS, 91400, Orsay, France
b   Laboratoire de Chimie Organique et Chimie Thérapeutique, FMPO-UCAD Université Cheikh Anta-Diop, Dakar, Senegal
,
Matar Seck
b   Laboratoire de Chimie Organique et Chimie Thérapeutique, FMPO-UCAD Université Cheikh Anta-Diop, Dakar, Senegal
,
Bruno Figadère
a   BioCIS, Université Paris-Saclay, CNRS, 91400, Orsay, France
,
Laurent Ferrié∗
a   BioCIS, Université Paris-Saclay, CNRS, 91400, Orsay, France
› Author AffiliationsI.C. thanks the Ministère français des affaires étrangères for providing a French–Senegalese cooperation fellowship.
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Abstract

Amphidinolide U is a cytotoxic marine macrolide isolated from Amphidinium sp., sharing 75% of the amphidinolide C backbone. We report here a synthetic study of the C1–C12 fragment of amphidinolide U. The C6–C12 pattern was built using consecutive regioselective ring opening of epoxides, a directed reaction to control newly formed stereogenic centers. In parallel, the C1–C5 moiety was constructed by taking advantage of a symmetrical diol. Attempts to cross-couple the C1–C5 and C6–C12 fragments by using a Suzuki cross-coupling reaction led to poor conversion rates. The same transformation on a close substrate model used during past studies on the total synthesis of amphidinolides F and C2 was successful. These contrasting results could be explained by a presumed steric hindrance of the protecting group adjacent to the vinyl function involved in the cross-coupling reaction. Our investigations will stimulate the optimization of C(sp2)–C(sp3) cross-coupling reactions with bulky substrates, with the aim of achieving a total synthesis of amphidinolide U.

Key words

amphidinolides - polyketides - total synthesis - Suzuki cross-coupling - epoxides - protecting groups

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2099-6389.
  • Supporting Information


Publication History

Received: 30 April 2023

Accepted after revision: 24 May 2023

Accepted Manuscript online:
24 May 2023

Article published online:
06 July 2023

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