Diphenyl Phosphorazidate peptide synthesis

The procedure described is essentially that of Shioiri and Yamada. Diphenyl phosphorazidate is a useful and versatile reagent in organic synthesis. It has been used for racemlzatlon-free peptide syntheses, thiol ester synthesis, a modified Curtius reaction, an esterification of a-substituted carboxylic acld, formation of diketoplperazines, alkyl azide synthesis, phosphorylation of alcohols and amines,and polymerization of amino acids and peptides. - Furthermore, diphenyl phosphorazidate acts as a nitrene source and as a 1,3-dipole.An example in the ring contraction of cyclic ketones to form cycloalkanecarboxylic acids is presented in the next procedure, this volume. 

Another cycloamidation reagent which has found wide use is diphenyl phosphorazidate (DPPA)J9 In their synthesis of K-13 (9), Boger and co-workers used DPPA to form the 17-membered cyclic peptide 13 (Scheme 3) J4,5 ... 

Yamada S, Ikota N, Shioiri T. Diphenyl phosphorazidate (DPPA) and diethyl phosphorocyanidate (DEPC). Two new reagents for solid-phase peptide synthesis and their application to the synthesis of porcine motilin. J. Am. Chem. Soc. 1975 97 7174-7175. 

Ikota N, Shioiri T, Yamada S, Tachibana S. Amino acids and peptides. XXXI. Phosphorus in organic synthesis. XVIII. Synthesis of porcine motilin by the solid-phase method us- 41. ing diphenyl phosphorazidate (DPPA) and diethyl phosphoro-cyanidate (DEPC). Chem. Pharm. Bull. 1980 28 3347-5336. 

Diethyl phosphorocyanidate continues to be exploited for the purposes of conventional organic synthesis. Reported applications of the compound include a new conversion of carboxylic acids into esters or amides and also a ring-expansion reaction of 1,3-thiazoles in the penicillin series. Diphenyl phosphorazidate has been employed in a modified Curtius reaction/ in peptide synthesis, and for... 

The use of diphenyl phosphorazidate in modified Curtius reactions in the synthesis of peptides has been described... 

Use of diphenyl phosphorazidate and diethyl phosphorocyanidate as coupling agents for solid-phase peptide synthesis. 

General. Diphenyl phosphorazidate is a readily available, nonexplosive, and relatively stable azide widely used as a reagent in peptide synthesis, " and as a versatile reagent in a wide array of organic transformations. DPPA has been successfully utilized in the synthesis of a-amino acids and o-aryl carboxylic acids direct preparation of thiol esters from carboxylic acids and thiols the stereospecific preparation of alkyl azides and the phosphorylation of alcohols and amines The application of DPPA in a modified Curtius reaction permits a simple one-step conversion of carboxylic acids to urethanes under mild reaction conditions. DPPA acts as a nitrene source, and can undergo 1,3-dipolar cycloaddition reactions. The Curtius degradation of carboxylic acids in the presence of f-butanol gives the Boc-protected amine directly (eq 1). 

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