Dipartimento di Scienze Farmaceutiche, Università della Calabria, Via Ponte P. Bucci Cubo 15/C, I-87036 Arcavacata di Rende (CS), Italy.
J Org Chem. 2010 Mar 5;75(5):1386-92. doi: 10.1021/jo901643f.
In this paper we describe a simple and efficient solution-phase synthesis of N-methyl-N-nosyl-alpha-amino acids and N-Fmoc-N-methyl-alpha-amino acids. This represents a very important application in peptide synthesis to obtain N-methylated peptides in both solution and solid phase. The developed methodology involves the use of N-nosyl-alpha-amino acids with the carboxyl function protected as a phenacyl ester and the methylating reagent diazomethane. An important aspect of this synthetic strategy is the possibility to selectively deprotect the carboxyl function or alternatively both amino and carboxyl moieties by using the same reagent with a different molar excess and under mild conditions. Furthermore, the adopted procedure keeps unchanged the acid-sensitive side chain protecting groups used in Fmoc-based synthetic strategies.
在本文中，我们描述了一种简单有效的 N-甲基-N-硝酰基-α-氨基酸和 N-Fmoc-N-甲基-α-氨基酸的溶液相合成方法。这在肽合成中是一个非常重要的应用，可以在溶液相和固相都得到 N-甲基化的肽。所开发的方法学涉及使用 N-硝酰基-α-氨基酸，其羧基功能被保护为苯甲酰酯，以及甲基化试剂重氮甲烷。该合成策略的一个重要方面是可以通过使用不同摩尔过量的相同试剂并在温和条件下选择性地脱保护羧基功能或替代地同时脱保护氨基和羧基部分。此外，所采用的方法保持了 Fmoc 基合成策略中使用的酸敏感侧链保护基不变。
