Amino acids and processes for making peptides using same

A method of synthesizing a peptide by chain elongation from the C-terminus thereof, which method comprises

• subjecting an .alpha.-amino acid having the formula:
• ##STR53## to nitration conditions by forming a reaction mixture which includes said amino acid, concentrated sulfuric acid and concentrated nitric acid having at least about 2 moles of HNO.sub.3 for each mole of .alpha.-amino acid and maintaining said reaction mixture at a temperature of about 5.degree. C. or below to cause said nitration to occur predominantly at the 4-position,
• reacting said 4NO.sub.2 -substituted product with an appropriate reagent to add an amino-protecting group to said .alpha.-amino acid,
• treating said protected amino acid to hydrogenate said substituted nitro moiety and transform it to an amino moiety,
• dissolving said hydrogenated .alpha.-amino acid in a suitable solvent and reacting it with diphenylcyanocarbonimidate to form a cyanoguanidino intermediate,
• thereafter reacting said cyanoguanidino intermediate with hydrazine to create a 3-amino, 1,2,4 triazole moiety attached to the 4-position of the phenyl ring of the side chain of said .alpha.-amino acid,
• forming a peptide intermediate with a protected .alpha.-amino group at its N-terminus, and
• deprotecting the .alpha.-amino group of said peptide intermediate and reacting same to form an amide bond with said .alpha.-amino acid having said triazole side chain.

A method of synthesizing a peptide by chain elongation from the C-terminus thereof, which method comprises

• forming a peptide intermediate which includes the amino acid sequence Leu-Lys(Ipr)-Pro-D-Ala,
• causing a first reaction between the .alpha.-amino group of Leu at the N-terminus of said peptide intermediate with the .alpha.-carboxyl group of Boc-D-Aph(3-amino, 1,2,4 triazole) to elongate said peptide intermediate,
• removing said Boc protecting group from said elongated peptide intermediate,
• carrying out a second reaction with the e-carboxyl group of Boc-L-Aph(3-amino, 1,2,4 triazole) to further elongate said elongated peptide intermediate,
• removing said Boc protecting group and sequentially adding Boc-Ser, Boc-D-3PAL, Boc(4Cl)D-Phe and Boc-.beta.-D-2Nal to create a decapeptide intermediate,
• removing the Boc protecting group from the N-terminus of said decapeptide intermediate and acetylating said deprotected N-terminus, and
• removing any remaining protecting groups to provide the decapeptide Ac-.beta.-D-2NAL-(4Cl)D-Phe-D-3PAL-Ser-Aph(3-amino, 1,2,4 triazole)-D-Aph(3-amino, 1,2,4 triazole)-Leu-Lys(isopropyl)-Pro-D-Ala-NH.sub.2.