Carboxylic acids, azides preparation peptide synthesis with

Unfortunately, A-(9-fluorenylmethoxycarbonyl)aziridine-2-carboxylic acid cannot be used in peptide synthesis, since N-deprotection of the respective peptides with secondary amines leads to oxazoline or dehydroamino acid side products. Similarly, N-(tert-butoxy-carbonyl)aziridine-2-carboxylic acid is inappropriate due to the instability of the aziridine moiety to TFA treatment. Attempts to convert A-tritylaziridine-2-carboxylic acid into homogenous and stable active esters as useful intermediates in peptide synthesis leads to positive results only in the case of the pentafluorophenyl ester. 47 Consequently, this active ester seems to be the method of choice for acylating peptides. The related Abhydroxysuc-cinimide and A-3-hydroxy-4-oxo-3,4-dihydro-l,2,3-benzotriazine ester could not be isolated in pure form and have therefore been used as crude products. 47 Access to 2-carbonylazir-idine peptides is also possible by carbodiimide-mediated coupling. Additionally, alkylamides of A-tritylaziridine-2-carboxylic acid are prepared by the azide method,1 5 yet this method fails in peptide coupling steps. 85 ... 

Carboxylic acid azides give rise to three different reactions under different conditions. Azide coupling (equation 9) was the earliest method in peptide synthesis and is still one of the most important in fragment condensation and preparation of cyclic peptides due to its almost complete lack of racemization. At elevated temperatures a frequent side reaction is the Curtius rearrangement. Trapping of the intermediate isocyanate with amines (equation 10) gives urea derivatives and with carboxylic acids rearranged amides are obtained (equation 11). ... 

The mono-esters thus prepared have been used by Bolm et al. for selective synthesis of two-stranded peptidic structures with parallel arrangement of the peptide strands [12]. They also enable easy access to unnatural /i-amino acids in enan-tiomerically pure form. The latter reaction sequence involves conversion of the carboxyl group to an acyl azide and subsequent Curtius degradation [11, 13, 14]. 

Esterification at room temp, with tetrachloroaluminic acid ether complex has been described The alcoholysis of a-mono-alkylacetoacetates to the corresponding esters and alkyl acetates has been accomplished with excellent yields A new modification of the Curtius degradation avoids the prepn. of acid chlorides by using in their place carboxylic alkoxyformic anhydrides intermediates well-known in peptide chemistry. Among recent developments in this latter field are the use of mixed anhydrides prepared with diphenylketene an improved peptide synthesis via azides prepared with nitrosyl chloride or butyl nitrite instead of aq. sodium nitrite and a rapid synthesis directly from acid hydrazides with N-bromosuccinimide Oligopeptides and /5-lactams have been synthesized from simple starting materials and isonitriles,... 

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