Formation of by-products during sodium–liquid ammonia reduction in peptide chemistry

Sodium-liquid ammonia reduction in peptide chemistry

“…(c) Similarly to the cleavage of the S-methyl group, the rate of salt formation of the carboxamide group is slower by approximately 1-2 orders of magnitude than that of the neutralization of the ammonium ion. [29][30][31] The salt formation of the carboxamide group is competitive with its reduction to the alcohol derivative.31 Both of these reactions can be prevented if sodium is not used in an excess during the deprotections.…”

“…Our studies in the field of sodium-liquid ammonia reductions resulted in three practical applications, (a) The first is the optimization of the reduction in the synthesis of biologically active peptides.198 (b) Recognizing the competitiveness of the salt formation and the reduction of the carboxamide group to an alcohol derivative, [29][30][31]195,196 we developed two theoretically equivalent methods for the complete conversion of the carboxamide group to an alcohol derivative. It must be stressed that because of this competitiveness no complete reduction can be reached, no matter how large is the sodium excess.…”

ChemInform Abstract: STUDIES ON PEPTIDES. CXIII. SYNTHESIS OF THE HEPTACOSAPEPTIDE AMIDE CORRESPONDING TO THE ENTIRE AMINO ACID SEQUENCE OF CHICKEN SECRETIN

“…The solvent was evaporated and the product was purified by procedure B, followed by recrystallization from MeOH and AcOEt; (12.80 g, 18.1 mmol) was treated with TFA-anisole (30 ml-9.8 ml) and the NQdeprotected peptide isolated as usual was dissolved in DMF (1 50 ml) and the solution was neutralized with Et,N. The desired eluates (Rf, 0.82) were concentrated and the residues were treated with ether to afford a solid; yield 10 The solvent was evaporated and the residue was dissolved in AcOEt.…”

“…Presence of the Met residue seems one of the structural features of chicken secretin, since the porcine hormone possesses no sulfur-containing amino acid. The sodium in liquid ammonia deprotecting procedure (9) which they employed is known to involve various and inevitable side reactions, as recently reexamined in detail by Schon et al (10). We have synthesized the heptacosapeptide amide corresponding t o the entire amino acid sequence of this newly found secretin from avian origin by a method different to the one reported preliminarily by Mochizuki et al (8).…”

Re-examination of a versatile hydantoins synthesis

“…as precursors to α-amino acid and pyruvic acid derivatives. [1][2][3][4] Hydantoins, originally observed as undesired by-products in the synthesis of peptides, [5][6][7] and they present a broad range of biological activity. [8][9][10][11][12][13][14][15][16][17][18] Hydantoins substituted at C-5 are important medicinal compounds.…”