Unson C G, Erickson B W
Int J Pept Protein Res. 1983 Jul;22(1):50-6. doi: 10.1111/j.1399-3011.1983.tb02067.x.
Synthesis and characterization of a dozen derivatives of ornithine and arginine bearing 2-methyl or 2-carboxymethyl substituents are described. These substituents were introduced by dilithiation of 3-(4-methoxybenzylidineamino)-2-piperidinone with lithium diisopropylamide followed by regiospecific alkylation at C-3 with iodomethane or ethyl bromoacetate. 2-Methyl-D,L-ornithine was obtained in three steps from 3-amino-2-piperidinone in 68% overall yield, and 2-carboxymethyl-D,L-ornithine was isolated in 56% overall yield. 2-Methyl- and 2-carboxymethyl-D,L-arginine were obtained by mild acid hydrolysis to remove the 4-methoxybenzylidine group, N-acylation with 4-toluenesulfonyl chloride, mild alkaline hydrolysis of the lactam ring and the ester group, guanidination of the 5-amino group with O-methylisourea, and strong acid hydrolysis to remove the 4-tolunenesulfonyl group. Several of these compounds are inhibitors of carboxypeptidase B.
本文描述了十二种带有2-甲基或2-羧甲基取代基的鸟氨酸和精氨酸衍生物的合成与表征。这些取代基是通过用二异丙基氨基锂将3-(4-甲氧基亚苄基氨基)-2-哌啶酮双锂化，然后在C-3位用碘甲烷或溴乙酸乙酯进行区域特异性烷基化引入的。2-甲基-D,L-鸟氨酸由3-氨基-2-哌啶酮经三步反应制得，总收率为68%；2-羧甲基-D,L-鸟氨酸的总收率为56%。通过温和酸水解以除去4-甲氧基亚苄基基团、用对甲苯磺酰氯进行N-酰化、对内酰胺环和酯基进行温和碱性水解、用O-甲基异脲对5-氨基进行胍基化以及用强酸水解以除去对甲苯磺酰基团，从而得到2-甲基-D,L-精氨酸和2-羧甲基-D,L-精氨酸。这些化合物中的几种是羧肽酶B的抑制剂。
