N- PROTECTED AMINO ACIDS AND PEPTIDES

摘要

1368401 N-protected amino acids and peptides ELI LILLY & CO 14 April 1972 [15 April 1971] 17373/72 Heading C2C Novel compounds III in which R is H, Cl, C 6 H 5 or phenyl substituted by 1-4 C alkyl, 1-4 C alkoxy or halo; R 1 is H or 1-4 C alkyl; R 2 is 1-4 C alkyl or R 1 and R 2 together with the C to which they are attached form a 5-7 membered carbocyclic ring; R 4 and R 6 are H or 1-4 C alkyl; R 5 and R 7 are H, 1-4 C alkyl, hydroxy-1-4 C alkyl, protected hydroxy-1-4 C alkyl, amino-1-4 C alkyl, protected amino 1-4 C alkyl, mercapto- 1-4 C alkyl, protected mercapto-1-4 C-alkyl, 1-4 C alkylthio alkyl, carboxy-1-4 C alkyl, protected carboxy-1-4 C alkyl, guanidino-1-4 C alkyl, protected guanidino-1-4 C alkyl, guanidino-oxy-1-4 C alkyl, imidazolylmethyl, protected imidazolylmethyl, indolylmethyl, protected indolylmethyl, phenyl, 4-hydroxyphenyl or protected 4-hydroxyphenyl; R 8 is OH, OCH 3 , OC 2 H 5 , O-C(CH 3 ) 3 , Cl 3 CCH 2 O, succinimido-oxy, phenoxy, benzyloxy, 4-nitrobenzyloxy, 2,4,5-trichlorophenoxy, pentachlorophenethoxy, or pentafluorophenoxy and the acid addition, alkali or alkaline earth metal, ammonium and amine salts; m and n are 0 or 1-4; and p is 0 or 1-14; are prepared by conventional methods of peptide synthesis. The protecting group R-C#C-C(R 1 )(R 2 )-OCO- may be removed by catalytic hydrogenolysis at neutral pH under mild conditions to yield the corresponding N-unprotected peptides or amino acids. 1 - Phenyl - 3 - methyl - 1 - butyn - 3 - yl phenyl carbonate is prepared by reaction of the butyn- 3-ol with phenyl chloroformate. 3-Methyl-1- butyn - 3 - yl 2,4,5 - trichlorophenyl carbonate and 3 - methyl - 1 - pentyn - 3 - yl 2,4,5 - trichlorophenyl carbonate are similarly prepared. 3 - Methyl - 1 - butyn - 3 - oxycarbonyl chloride and 1 - ethynyl - 1 - cyclohexanyloxycarbonyl chloride are prepared by reaction of the appropriate alcohol with SOCl 2 .