Cyclic Peptides from Linear Unprotected Peptide Precursors through Thiazolidine Formation

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• 作者：Paolo Botti ; T. David Pallin ; and James P. Tam
• 刊名：Journal of the American Chemical Society
• 出版年：1996
• 出版时间：October 23, 1996
• 年：1996
• 卷：118
• 期：42
• 页码：10018 - 10024
• 全文大小：165K
• 年卷期：v.118,no.42(October 23, 1996)
• ISSN：1520-5126

文摘

We describe a general method for the preparation of cyclicpeptides by intramolecular thiazolidine formationfrom linear, unprotected peptide precursors. The precursorscontain a protected 1,2-aminothiol from an N-terminalcysteine and a 1,2-amino alcohol or 1,2-diol as a masked aldehyde.Thiazolidine formation was effected by oxidationof the 1,2-amino alcohol or 1,2-diol by sodium periodate to give analdehyde, followed by deprotection of the masked1,2-aminothiol. The cyclization could be effected atconcentrations as high as 20 mM and was free from anypolymerized side products. Such high efficiency ofmacrocyclization may be attributed to the ring-chain"tautomerismof the open chain amino-aldehyde precursor that favors a macrocyclicthiazolidine ring. Thiazolidine formation wasfurther exploited as a capture device to position the N and C terminicovalently close together and then to allow aproximity-driven O to N acyl transfer through a novel tricyclic ringcontraction to yield an all amide, end-to-endcyclic lactam. These macrocyclization methods have been applied tothe synthesis of cyclic peptides containing 5to 26 amino acids.