Pallai P V, Richman S, Struthers R S, Goodman M
Int J Pept Protein Res. 1983 Jan;21(1):84-92. doi: 10.1111/j.1399-3011.1983.tb03081.x.
Partial retro-inverso modification of biologically active peptides is described as a topochemical alteration of the backbone to prevent enzymatic degradation. The preparation of gem-diaminoalkyl residues from peptide amides using the reagent [bis(trifluoroacetoxy)iodo]benzene (TIB) is discussed. Treatment of N-t-butyloxycarbonyl tyrosine and N-t-butyloxycarbonyl tryptophan with this reagent led to decomposition of the protected amino acids. Protecting the tyrosine and tryptophan residues by t-butyl ether and Nin-formyl groups, respectively, prevented decomposition and led to good yields of the desired products. Racemic 2-alkylmalonyl diastereomers were found to be separable by HPLC. The chiral stability of peptides containing optically active malonyl residues was investigated under simulated physiological conditions. Synthetic considerations for the incorporation of gem-diaminoalkyl and 2-alkylmalonyl residues into larger peptides to yield partially modified retro-inverso peptide analogs are presented.
生物活性肽的部分反向修饰被描述为骨架的拓扑化学改变，以防止酶促降解。讨论了使用试剂[双（三氟乙酰氧基）碘]苯（TIB）从肽酰胺制备偕二氨基烷基残基。用该试剂处理N-叔丁氧羰基酪氨酸和N-叔丁氧羰基色氨酸导致受保护氨基酸的分解。分别用叔丁基醚和N-甲酰基保护酪氨酸和色氨酸残基可防止分解，并得到所需产物的良好产率。发现外消旋2-烷基丙二酰非对映异构体可通过HPLC分离。在模拟生理条件下研究了含有光学活性丙二酰残基的肽的手性稳定性。提出了将偕二氨基烷基和2-烷基丙二酰残基掺入更大的肽中以产生部分修饰的反向肽类似物的合成考虑因素。
