Peptide hydrobromides peptides

The above mentioned peptide salts include, for instance, hydrochlorides, hydrobromides, acetates, fluoroacetates, such as trifluoroacetate, and chloroacetates such as dichloroacetate. 

The treatment of a N-substituted hydrazine hydrobromide successively with the a,a-dicyano-epoxide 91 and with TV-methyl hydrazine results in the racemic a-hydrazino hydrazide 92 (Scheme 29)/111 Repeating the above two reactions allows the elongation of 92 into the racemic (hydrazide) peptide 93/1121 A derived procedure, with ClCH2COCl instead of 91, is applied to the synthesis of the first (hydrazide) cyclotripeptide 94 (R1 = 4-C1C6H4 or 4-MeQlLi) (Scheme 30), by coupling of the N-terminal chloroacetyl and C-terminal hydrazine groups/113 It has been later extended to the synthesis of linear (hydrazide) polypeptides/114 It is noteworthy that the a-carbon is racemic in all of the above cases. 

On a preparative scale the primary amides gave products different from the lactones obtained from the allylglycine peptides. They were originally thought to be iminolactone hydrobromides (Craig, 1952), however, their... 

A saturated soln (50 g) of dry HBr in glacial AcOH (36%) was added to the Z-protected amino acid or peptide derivative (10 g) in a reaction flask protected with a CaCb tube. Immediate formation of CO2 begins in some cases in markedly exothermic manner. The mixture was allowed to stand at rt with occasional shaking for Ih, then dry Et20 was added to precipitate the amine hydrobromide. The supernatant liquid was decanted and the solid triturated with Et20, filtered, and washed with Et20. 

M8. Maskaleris, M. L., Sevendal, E. S., and Kibrick, A. C., Carbobenzoxy derivatives of amino acids and peptides Instant thin-layer chromatography as hydrobromides. J. Chromalog. 23, 403-409 (1966). 

By using active peptide esters with high molecular ester components, inter-molecular aminolysis can be suppressed. — E Glycyl glycine cross-linked poly-(4-hydroxy-3-nitrostyrene) ester hydrobromide suspended in dimethylformamide, neutralized with triethylamine, allowed to stand 12 hrs. at room temp., and the resulting poly-4-hydroxy-3-nitrostyrene removed by filtration diketo-piperazine. Y 75%. F. e. and ester components s. M. Fridkin, A. Patchornik, and E. Katchalski, Am. Soc. 87, 4646 (1965) peptides s. T. Wieland and G. Birr, Ang. Gh. 78, 303 (1966) with active a-aminocarboxylic acid polyphenolesters s. M. Fridkin, A. Patchornik, and E. Katchalski, Am. Soc, 88, 3164 (1966). 

In another method, the free amino groups in the peptide-resin are converted to the corresponding hydrochloride or hydrobromide by reaction with the respective pyridinium halide (Dorman and Love, 1969 Losse and Ulbrich, 1971 Losse, 1971). The halide ion is then displaced from the resin by triethylamine and measured titrimetrically. The speed and sensitivity of the method has been improved (Hancock et al., 1973) by using pyridineH Cl, which enables the released chloride to be determined by measurement of radioactivity and which allows the method to be automated. Just as the free amino groups in the resin can be converted into their hydrochlorides, salt formation with other radiolabeled acids, e.g., l-[ K ]chloroacetic acidor [ S] sulfuric acid (Beyerman tz/., 1973), has been used to determine the amino group content of the resin. 

Isobutyl chloroformate added at —5° to a soln. of benzyloxycarbonyl-L-proline and triethylamine in dry chloroform, stirred 0.5 hr., L-leucine p-nitrophenyl ester hydrobromide added followed by gradual addition of a soln. of triethylamine in chloroform over a period of 15 min., kept 3 hrs. at 0-10° and 1 hr. at room temp., then glycine ethyl ester hydrochloride and triethylamine added with stirring, and kept 2 days at room temp. -> benzyloxycarbonyl-L-prolyl-L-leucylglycine ethyl ester. Y 84%.—The difunctionality of aminoacid active esters and the different reaction rates at the amino and ester ends allow the direct synthesis of tripeptides by two consecutive reactions. F. e., also isolation of intermediates, s. M. Goodman and K. G. Stueben, Am. Soc. 81, 3980 (1959). Peptide synthesis... 

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