Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Published in: Beilstein journal of organic chemistry Vol. 15; no. 1; pp. 577 - 583
• Main Authors: Lang, Jan Hendrik, Lindel, Thomas
• Format: Journal Article
• Language: English
• Published: Germany Beilstein-Institut zur Föerderung der Chemischen Wissenschaften 28-02-2019; Beilstein-Institut
• Subjects: Alcohol; Aluminum; Amino acids; Chemical industry; Chemistry; Cytotoxicity; Full Research Paper; Jasplakinolide; L-Alanine; Labeling; marine natural products; Natural products; Negishi coupling; Peptides; polyketides; Propylene oxide; stereoselective synthesis; Threonine; Negishi coupling; marine natural products; polyketides; jasplakinolide; stereoselective synthesis
• ISSN: 1860-5397; 2195-951X; 1860-5397
• DOI: 10.3762/bjoc.15.53

The synthesis of the polyketide section present in the potently cytotoxic marine cyclodepsipeptide jasplakinolide and related natural products, geodiamolides and seragamides, is reported. The key step is a Negishi cross coupling of (
)-(3-methoxy-2-methyl-3-oxopropyl)zinc(II) bromide and an (
)-iodoalkene that was synthesized via an aluminium ester enolate attack at (
)-propylene oxide. The overall synthesis comprises nine steps with an overall yield of 21%. It proved to be possible to liberate the free 8-hydroxynonenoic acid and to couple it with a protected tripeptide composed of L-alanine,
-dimethyl-D-iodotyrosine, and TIPS-protected L-threonine, which occurs as partial structure of seragamide A. The tripeptide section of seragamide A was assembled by solution-phase synthesis and an open-chain analogue of the natural product was obtained.