Diethyl phosphorocyanidate peptides

In addition to the most common methods for cyclization of linear peptides (vide supra), alternative coupling reagents have been used with varying success such as BOP-Cl, 140-142 norborn-5-ene-2,3-dicarboximido diphenyl phosphate (NDPP),119-143-144 pentafluorophenyl diphenylphosphinate (FDPP),1145-148 diethyl phosphorocyanidate (DEPC), 138-149 or T3P.197-1501... 

More than a decade ago, Yamada and coworkers [70] developed two efficient reagents, diphenylphosphoryl azide (DPPA) and diethyl phosphorocyanidate (DEPC), for peptide done construction. The exact mechanism still remains speculative. For example, in the case of DPPA, the intermediacy of the carboxylic acid azide is tentative, but it seems attractive to consider a concerted process as shown in Figure 2 [70 a]. 

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. 

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... 

Shioiri, T., Yokoyama, Y, Kasai, Y, andYamada. S.. Phosphorus in organic synthesis. Part 11. Amino acids and peptides. Part 21. Reaction of diethyl phosphorocyanidate (DEPC) with carboxylic acids. A new synthesis of carboxylic esters and amides. Tetrahedron. 32. 2211. 1976. 

The MTX y-peptide (VIII.239), in which the y-carboxyl is joined to 4-ami-nobutyric acid, has been synthesized [352] as a de(carboxy) analogue of MTX -I- G,. Condensation of a-benzyl L-glutamate with MeAPA by the diethyl phosphorocyanidate procedure gave a 94% yield of a-benzyl MTX, which on reaction with methyl 4-aminobutyrate in the presence of diphenylphosphoryl azide and subsequent ester hydrolysis with Ba(OH)2 was converted to (VIII.239) in 50% overall yield. 

Another peptide derivative of MTX was prepared [362] with the aim of covalently attaching it to antibodies. Condensation of oxidized glutathione tetraethyl ester with 4-amino-4-deoxy-A °-methylpteroic acid with the aid of diethyl phosphorocyanidate afforded the tetraethyl ester (VIII.262) (47% yield). Hydrolysis of the ester groups with Ba(OH)2 followed by ion-exchange chromatography in the presence of 2-mercaptoethanol gave a crude product which was assumed to be the reduced tripeptide. On further purification by gel filtration without 2-mercaptoethanol, this compound underwent spontaneous oxidation to disulphide (VIII.263). In a model experiment, an IgG, monoclonal antibody directed against human transferrin receptor was activated by reaction with A-succinimidyl-3-(2-pyridyldithio)propionate, and con-... 

Solid-phase peptide synthesis. Both diethyl phosphorocyanidate and the related diphenylphosphoryl azide have been shown to be useful in solid-phase peptide synthesis. They have been used successfully for synthesis of porcine motilin (composed of 22 amino acids). 

PEPTIDES Benzotriazolyloxytris(dimethylamino)-phosphonium hexafluorophosphate. Diethyl phosphorocyanidate. Diphenylphosphinyl chloride. 4,6-Diphenylthienol3,4-dJ-dioxol-2-one-5,S-dioxide. Thioglycolic add. 

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

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