Mauger A B, Stuart O A
Research Foundation of the Washington Healthcare Corporation, Washington, D.C.
Int J Pept Protein Res. 1987 Oct;30(4):481-8. doi: 10.1111/j.1399-3011.1987.tb03356.x.
The pentapeptide lactone Cbz-(Thr-D-Val-Pro-Sar-MeAla-) was synthesized in order to observe the behavior of the unprotected lactone resulting from its hydrogenolytic deprotection. Closely related peptide lactones have been reported as intermediates in total syntheses of actinomycin D and its analogues, despite the fact that unprotected and unprotonated O-peptides of serine and threonine are known to undergo rapid O,N-acyl shift. In the present study the peptide lactone was seen to undergo a slow O,N-acyl shift, in a matter of hours, to the known cyclic pentapeptide. This contrasted with the rapid rearrangement of a model O-peptide, O-hippuryl-L-threonine methyl ester. This slowness of an O,N-acyl shift in a cyclic system presumably results from higher energy barriers of conformational origin. It explains the suitability of unprotected peptide lactones for the syntheses of actinomycins and other peptide lactone antibiotics which have appeared in the literature.
合成了五肽内酯Cbz-(苏氨酸- D-缬氨酸-脯氨酸-肌氨酸-甲基丙氨酸-)，以观察其氢解脱保护后产生的未保护内酯的行为。尽管已知丝氨酸和苏氨酸的未保护且未质子化的O-肽会发生快速的O,N-酰基转移，但密切相关的肽内酯已被报道为放线菌素D及其类似物全合成中的中间体。在本研究中，观察到该肽内酯在数小时内缓慢地发生O,N-酰基转移，生成已知的环状五肽。这与模型O-肽O-马尿酸-L-苏氨酸甲酯的快速重排形成对比。环状体系中O,N-酰基转移的这种缓慢可能是由构象起源的较高能量屏障导致的。这解释了未保护的肽内酯适用于文献中出现的放线菌素和其他肽内酯抗生素的合成。
