SYNTHESIS OF [DSER(TBU)(6),DESGLY(1O)]GNRH-ET WITHOUT SIDE-CHAIN PROTECTION

A gonadoliberin superagonist, [DSer(tBu)(6),desGly(10)]GnRH-Et (5), w as obtained in solution by connecting segments, Glp-His-Trp-Ser-Tyr-N2 H3 (1) and Z-DSer(tBu)-Leu-Arg(AcOH)-Pro-NHEt (4) (Scheme 1), which we re produced without protecting their side-chain functions, in high yie ld and purity. Segment 1 was synthesized from DHis diastereoisomer-fre e Glp-His-Trp-N2H3 and Boc-Ser-Tyr-OMe. Segment 4 was prepared step-by -step from the C-terminus, with DCC/HOBt as the coupling reagent inclu ding HOBt as the guanidine protection simultaneously, with only purifi cation of the intermediates by edulcoration, and finally chromatograph ed on a silica gel short column. Z-Arg(H+)-NMe(2), reported by others as a si de-product of Z-Arg(H+)-Pro-NHEt synthesis in DMF, was not obs erved. The crude final peptide 5 was purified on a silica gel short co lumn.