SOLID-PHASE SYNTHESIS OF N-METHYLAMIDES AND N-ETHYLAMIDES OF PEPTIDES USING PHOTOLYTICALLY DETACHABLE ((3-NITRO-4-((ALKYLAMINO)METHYL)BENZAMIDO)METHYL)POLYSTYRENE RESIN

A convenient method for the solid-phase synthesis of C-terminal peptide N-alkylamides using a photolytically detachable ((3-nitro-4-((alkylamino)methyl)benzamido)methyl)polystyrene support is described. The method involves prior incorporation of an alkylamine moiety into the i(3-nitro-4-(bromomethyl)benzamido)methyl)-polystyrene resin, on which the peptides were assembled and subsequently cleaved in the form of the peptide N-alkylamides by photolysis. The N-alkylamino group acts as an anchoring function for the peptide as well as a latent reagent function for the C-terminal modification of the attached peptide. The method is particularly useful if the peptide contains Asp or Glu with a benzyl ester side chain protecting group. The synthetic applicability of the method is illustrated with the solid-phase synthesis of N-alkylamides of a few model peptides in 70-77% yields and analogues of the luteinizing hormone-releasing hormone in 48-56% yield. © 1990, American Chemical Society. All rights reserved.