METHOD OF SYNTHESIS OF PEPTIDEAMIDE DERIVATIVES OR THEIR PHYSIOLOGICALLY COMPATIBLE ACETATES OR HYDROCHLORIDES Russian patent published in 1995 - IPC

FIELD: peptide chemistry. SUBSTANCE: product: derivatives of peptideamides of the formula (I) (X)_n-A-NH₂ where X - Ac-L (or D)-(Hal), p-Cl-L (or D)-Phe, L (or D)-Ser, L (or D)-Tyr, L (or D)-Trp, L (or D)-Ser(α-L-Phe), L (or D)-Leu, L (or D)-Arg, L (or D)-Pro, p-Slu, His, D-Ser(t-Bu); n = 3-10; A - azaglycine, or their biologically compatible acetates or hydrochlorides. Reagent 1: compound of the formula (II) where Y₁-Y₅ - hydrogen; C₁-C₄-alkoxy-group; -(CH₂)_m-C(O)-OH [radicals are similar or different but at least one of their is (CH₂)_n-C(O)-OH]; m = 1-3; R₁ - hydrogen; 4-methoxyphenyl. Reagent 2: silyling agent of the group: tert.-butyldimethylsilyl chloride, tert.-butylphenylsilyl chloride, trimethylchlorosilane, bis-trimethylsilylacetamide. Reaction conditions: process is carried out in the medium of solvent following by treatment of silylated compound with chloroformic acid derivative. Compounds of the formula (III) R₂ were prepared where Y₁-Y₅ and R₁ - as indicated above; R₂ - halogeno (or nitro)-phenyl. These compounds were treated with hydrazide hydrochloride R₃-protected with corresponding α-amino acid (X meaning) where R₃, Fmoc Bpoc, BOC - are protective groups, in the medium of solvent with formation of compound of the formula (IV) . Protective group -BOC- is removed by hydrogenation on the Pt-catalyst. Before the further reaction protective group is conversed to the Fmoc- or BOC-protective group. Then compounds of the formula (IV) (at meaning R₃ - Fmoc, Bpoc-urethane-protective group) were copulated using usual peptide reagent (through -(CH)_n-C(O)-OH-grouping on the resin), protective group R₃ is split, and then step by step Fmoc- or Bpoc-protected α-amino acids (in some cases in the form of activated derivatives) were joined. After synthesis termination of peptide of the formula (I) the latter is released from resin by treatment with moderate force acid. Simultaneously or using conventional procedures temporarily added side chain protective groups were split. EFFECT: improved method of synthesis.