N-Methyl-N-nosyl-3-amino Acids

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• 作者：Emilia Belsito ; Maria L. Di Gioia ; Antonella Greco ; Antonella Leggio ; Angelo Liguori ; Francesca Perri ; Carlo Siciliano ; Maria C. Viscomi
• 刊名：Journal of Organic Chemistry
• 出版年：2007
• 出版时间：June 22, 2007
• 年：2007
• 卷：72
• 期：13
• 页码：4798 - 4802
• 全文大小：73K
• 年卷期：v.72,no.13(June 22, 2007)
• ISSN：1520-6904

文摘

N-Methyl-³-amino acids are important building blocks in the synthesis of biologically active molecules.A very simple and efficient approach to transform natural -amino acids into their corresponding N-methyl-³-amino acids is here presented. In the method, the key intermediates N-methyl-N-nosyl--aminoacyldiazomethanes are prepared in only one step, by a simple treatment of the corresponding N-nosyl--aminoacyl chlorides with diazomethane. The synthetic route takes advantage from the use of the nosylgroup. This N-masking moiety activates the NH function, and the N-methylation can directly occur duringthe acylation step of diazomethane, rendering useless a second step that instead is shown to be necessaryin all the classical procedures already reported for the preparation of N-methyl-³-amino acids. The Wolffrearrangement of N-methyl-N-nosyl--aminoacyldiazomethanes provides the corresponding N-methyl-N-nosyl-³-amino acids with total retention of the chiral configuration of the starting -amino acids. Noepimerization of the chiral carbon atom is observed also when N-methyl-N-nosyl-³-amino acids aretransformed into chlorides and coupled with -amino acid methyl esters to achieve model scaffolds forbiologically important modified peptides.