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. 2025 Mar 14;27(10):2284-2288.
doi: 10.1021/acs.orglett.5c00209. Epub 2025 Mar 6.

Synthesis of Leiodolide A Macrolactone

David R Williams  1 , Fese M Okha  1 , Sarah A Ward  1
Affiliations

Synthesis of Leiodolide A Macrolactone

David R Williams et al. Org Lett. .

Abstract

A convergent route toward the synthesis of leiodolide A (1) is described. Our studies explored reactions of the indium chloride-induced transmetalation of allylic stannane 32 for nucleophilic addition with nonracemic aldehyde 15. The stereoselective formation of the all-syn stereotriad was rationalized by an in situ isomerization to produce the Z-allylindium reagent for subsequent anti-Felkin addition. The inversion of C17 stereochemistry led to an effective π-allyl Stille cross coupling utilizing Z-alkenylstannane 11b. The Horner-Wadsworth-Emmons reaction provides macrolactone 37 which exhibits discrepancies as compared with reported NMR data for the purported leiodolide A.

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References

    1. Sandler JS; Colin PL; Kelly M Fenical W. Cytotoxic Macrolides from a New Species of the Deep-Water Marine Sponge Leiodermatium, J. Org. Chem. 2006, 71, 7245–7251. - PubMed
    1. Williams DR; Okha FM; Ward SA Studies Toward the Synthesis of Leiodolide A, Org. Lett. 2025, preceding paper. - PMC - PubMed
    1. Larivée A; Unger JB; Thomas M; Wirtz C; Dubost C; Handa S; Fürstner A The Leiodolide B Puzzle, Angew. Chem. Int. Ed. 2011, 50, 304–309. - PubMed

    1. Other reports that describe synthetic studies toward leiodolides include:Chellat MF; Proust N; Lauer MG; Stambuli JP Synthesis of Key Fragments of Leiodelide A, Org. Lett. 2011, 13, 3246–3249. Zhang X; Liu J; Sun X; Du Y An Efficient cis-Reduction of Alkyne to Alkene in the Presence of a Vinyl Iodide: Stereoselective Synthesis of the C22–31 Fragment of Leiodolide A, Tetrahedron, 2013, 69, 1553–1558.Ren R-G; Li M; Si C-M; Mao Z-Y; Wei B-G Studies Toward Asymmetric Synthesis of Leiodelide A, Tetrahedron Lett. 2014, 55, 6903–6906.Lee J; Panek JS Synthesis of the C13–C29 Fragment of Leiodolide A: Allylic Asymmetric Induction on the Stereochemical Course of Iodolactonization, Tetrahedron Lett. 2015, 56, 6868–6871.Wullschleger CW; Li A; Edenharter A; Altmann K-H Studies Towards the Synthesis of Leiodolide A, Synlett 2016, 27, 2726–2730.

    1. Gao Y; Hanson RM; Klunder JM; Ko SY; Masamune H; Sharpless KB Catalytic Asymmetric Epoxidation and Kinetic Resolution: Modified Procedures Including in Situ Derivatization, J. Am. Chem. Soc. 1987, 109, 5765–5780.
    2. Shao H; Zhu Q; Goodman M A New Asymmetric Synthesis of α-Methylcysteines via Chiral Aziridines, J. Org. Chem. 1995, 60, 790–791.

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