School of Chemical Sciences, The University of Auckland, 23 Symonds St, Auckland, 1142, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, 1142, New Zealand.
Org Biomol Chem. 2018 Jul 25;16(29):5286-5293. 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.
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.
塔洛尔内酯 A 的结构被提出，它是一种具有肽主链内羟胺部分的环庚七肽。最初尝试合成含有 C 末端 N-苄氧基甘氨酸残基的线性肽前体由于未报道的 N-苄氧基甘氨酸在树脂上还原为甘氨酸而出现问题。在重新定位肽环化点后，使用 Fmoc-固相肽合成成功制备了新的线性肽序列。随后的溶液相环化和保护基团的去除以良好的产率提供了合成的塔洛尔内酯 A。尽管合成的塔洛尔内酯 A 和天然产物的 NMR 数据不匹配，但使用二维 NMR 光谱进行的详细结构分析，以及使用另外两个环化位点对相同的合成材料进行重新合成，证实了我们的合成产物具有报道的塔洛尔内酯 A 的结构。
