| 摘要 |
Two processes (1) and (2) are claimed for preparing aza-cyclohexapeptides of formula (I) or their acid addition salts. R = CH2CH2NH2 or CH2CONH2; R1 = 9-21C alkyl, 9-21C alkenyl, (1-10C) alkoxyphenyl, (1-10C) alkoxynaphthyl or (1-10C) alkoxyterphenyl; H, 1-4C alkyl, 3-4C alkenyl, (CH2)nOH or (CH2)nNR4R5; n = 2-4; R3 = H, 1-4C alkyl, 3-4C alkenyl, (CH2)nOH or (CH2)nNR4R5, or NR2R3 = pyrrolidino, piperidino, morpholino or piperazino; R4,R5 = H or 1-4C alkyl; Q = N or O. Process (1) comprises: (a) reacting a cyclic peptide of formula (II) with phenylboronic acid, p-methoxyphenylboronic acid or methaneboronic acid to give the bis-phenylboronyl derivative of formula (III); (b) reducing to the amine and hydrolysing to give the deboronated amine compound of formula (IV); (c) reacting with thiophenol in a solvent to give the phenylthio derivative of formula (V), and (d) stereoselectively converting (V) into (I) by displacement of the phenylthio group. Ring A = the re mainder of the (II) molecule. Process (2) comprises: (a) reacting (II) with thiophenol to give the phenylthio derivative of formula (VI); (b) reacting with phenylboronic acid, p-methoxyphenylboronic acid or methaneboronic acid to give the phenylthio-phenylboronyl derivative of formula (IIIa); (c) reducing to the amine and hydrolysing to give (V), and (d) stereoselectively converting (V) into (I) by displacement of the phenylthio group. Intermediates (III), (IIIa), (V) and (VI) are new compounds. |
