Total synthesis of the proposed structure of talarolide A

• Published in: Organic & biomolecular chemistry Vol. 16; no. 29; pp. 5286 - 5293
• Main Authors: Zhang, Shengping, Rodriguez, Luis M. De Leon, Huang, Renjie, Leung, Ivanhoe K. H., Harris, Paul W. R., Brimble, Margaret A.
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 25.07.2018; Royal Society of Chemistry
• Subjects: Chemistry; Chemistry, Organic; Glycine; Magnetic resonance spectroscopy; Natural products; NMR spectroscopy; Peptide synthesis; Peptides; Physical Sciences; Protecting groups; Science & Technology; Structural analysis; Synthesis; Synthetic products; Two dimensional analysis; DEPSIPEPTIDE; PEPTIDES; HYDROXAMIC ACIDS; ALPHA-AMINO-ACIDS; INHIBITORS; AMYCOLATOPSIS SP; DERIVATIVES; N-HYDROXYLATION
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c8ob01230j

The proposed structure of talarolide A, a cycloheptapeptide featuring a hydroxamate moiety within the peptide backbone, was successfully synthesized. An initial attempt to synthesize a linear peptide precursor containing a C-terminal N-benzyloxy glycine residue was problematic due to an unreported on-resin reduction of N-benzyloxy glycine to glycine. After repositioning the peptide cyclization point, a new linear peptide sequence was successfully prepared using Fmoc-solid-phase peptide synthesis. Subsequent solution-phase cyclization and removal of protecting groups furnished the synthetic talarolide A in good yield. Despite the mismatch of the NMR data between the synthetic talarolide A and the natural product, a detailed structural analysis using 2D NMR spectroscopy, together with re-synthesis of the same synthetic material using two additional cyclization sites, confirmed that our synthetic product has the reported structure of talarolide A.