Cyclic peptides from linear unprotected peptide precursors through thiazolidine formation
Cyclic peptides from linear unprotected peptide precursors through thiazolidine formation
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DOI：
10.1021/ja954278g
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发表时间：
1996-10-23
影响因子：
15
通讯作者：
Tam, JP
中科院分区：
文献类型：
--
作者：
Botti, P;Pallin, TD;Tam, JP
我们描述了一种通过从线性、未受保护的肽前体形成分子内噻唑烷来制备环肽的通用方法。该前体含有来自 N 末端半胱氨酸的受保护的 1,2-氨基硫醇和作为掩蔽醛的 1,2-氨基醇或 1,2-二醇。通过用高碘酸钠氧化1，2-氨基醇或1，2-二醇得到醛，然后将掩蔽的1，2-氨基硫醇脱保护，从而形成噻唑烷。环化可以在高达 20 mM 的浓度下进行，并且不产生任何聚合副产物。如此高的大环化效率可能归因于有利于大环噻唑烷环的开链氨基醛前体的环链互变异构。噻唑烷的形成被进一步用作捕获装置，将 N 和 C 末端共价地靠近在一起，然后通过新型三环收缩进行邻近驱动的 O 到 N 酰基转移，产生全酰胺、端到端的环状内酰胺。这些大环化方法已应用于含有5至26个氨基酸的环肽的合成。
We describe a general method for the preparation of cyclic peptides by intramolecular thiazolidine formation from linear, unprotected peptide precursors. The precursors contain a protected 1,2-aminothiol from an N-terminal cysteine and a 1,2-amino alcohol or 1,2-diol as a masked aldehyde. Thiazolidine formation was effected by oxidation of the 1,2-amino alcohol or 1,2-diol by sodium periodate to give an aldehyde, followed by deprotection of the masked 1,2-aminothiol. The cyclization could be effected at concentrations as high as 20 mM and was free from any polymerized side products. Such high efficiency of macrocyclization may be attributed to the ring-chain'' tautomerism of the open chain amino-aldehyde precursor that favors a macrocyclic thiazolidine ring. Thiazolidine formation was further exploited as a capture device to position the N and C termini covalently close together and then to allow a proximity-driven O to N acyl transfer through a novel tricyclic ring contraction to yield an all amide, end-to-end cyclic lactam. These macrocyclization methods have been applied to the synthesis of cyclic peptides containing 5 to 26 amino acids.