Improved solid phase synthesis of luteinizing hormone releasing hormone analogues using 9-fluorenylmethyloxycarbonyl amino acid active esters and catalytic transfer hydrogenation with minimal sidechain protection and their biological activities.

Using mainly 9-fluorenylmethyloxycarbonyl amino acid 2, 4, 5-trichlorophenyl esters in the presence of 1-hydroxybenzotriazole and the solid support p-alkoxybenzyl alcohol resin, synthesis of luteinizing hormone releasing hormone analogues was carried out with minimal side-chain protection. Catalytic transfer hydrogenation was employed for removal of NO2 and Z-groups from Arg and < Glu respectively avoiding the use of HF and this led to good yields. An aromatic, hydrophilic amino acid, D-(p-hydroxyphenyl) glycine was incorporated into luteinizing hormone releasing hormone molecule along with other modifications. The agonistic as well as antagonistic activities of all the peptides have been studied.

New analogues of leucine-methionine-enkephalin.

Nine analogues of the opioid pentapeptides leucine-/ methionine-enkephalinamide, involving replacement of amino acid at position 5 or amino acids at positions 2 and 5, have been synthesized by the solid phase method using mainly 9-fluorenylmethyloxycarbonyl amino acid trichlorophenyl esters in the presence of 1-hydroxybenzotriazole, the solid support being the Merrifield resin. All the analogues were effective in inhibiting the electri cally stimulated contractions of the guinea pig ileum (in vitro) and one of them, tyrosyl-Dnorvalyl- glycyl-phenylalanyl-methioninamide was found to be about 82 times more active than morphine. They also exhibited analgesic activity as well as antidiarrhoeal activity in mice (in vivo).