Solid-Phase Synthesis of NMe-IB-01212, a Highly N-Methylated Cyclic Peptide

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• 作者：Eleonora Marcucci ; Judit Tulla-Puche ; Fernando Albericio
• 刊名：Organic Letters
• 出版年：2012
• 出版时间：January 20, 2012
• 年：2012
• 卷：14
• 期：2
• 页码：612-615
• 全文大小：259K
• 年卷期：v.14,no.2(January 20, 2012)
• ISSN：1523-7052

文摘

N-Methylation of peptides is an important synthetic tool in peptide-based medicinal chemistry. Herein, an optimized strategy for solid-phase synthesis of small but highly N-methylated cyclic peptides is described. The proposed route addresses several problems associated with the synthesis of peptides containing several sequential N-methyl-amino acids, such as in situ N-methylation, difficulty of acylation, epimerization, diketopiperazine formation, and stability at the NMe sites under trifluoroacetic acid exposure. The resulting NMe-IB-01212 exhibits micromolar activity and considerable stability.