Mauger A B, Stuart O A
Medlantic Research Foundation, Washington, D.C.
Int J Pept Protein Res. 1989 Sep;34(3):196-9. doi: 10.1111/j.1399-3011.1989.tb00230.x.
The N,O-acyl shift was investigated as a method for the synthesis of an O-peptide or peptide lactone from a linear or cyclic peptide respectively. Protected derivatives of glycyl-L-threonine could be converted to O-peptides by the action of HCl/dioxane at room temperature and N-acylated under conditions which precluded a reverse O,N-acyl shift. For effecting N,O-acyl shift in cyclo(Thr-D-Val-Pro-Sar-MeAla) this reagent was unsatisfactory and p-toluenesulfonic acid in dioxane at 80 degrees was used instead. The resulting crystalline peptide lactone p-toluenesulfonate salt was N-acylated with 3-benzyloxy-4-methyl-2-nitrobenzoyl chloride to afford a known intermediate in the synthesis of 5,5'-MeAla actinomycin D. This approach constitutes a novel synthetic route to actinomycins and potentially to other peptide lactone antibiotics.
研究了N，O-酰基转移反应，以此作为分别从线性肽或环肽合成O-肽或肽内酯的一种方法。甘氨酰-L-苏氨酸的保护衍生物在室温下可通过HCl/二氧六环的作用转化为O-肽，并在防止O，N-酰基转移逆转的条件下进行N-酰化。对于在环（苏氨酸-D-缬氨酸-脯氨酸-肌氨酸-甲基丙氨酸）中实现N，O-酰基转移，该试剂并不理想，因此改用80℃下二氧六环中的对甲苯磺酸。所得的结晶肽内酯对甲苯磺酸盐用3-苄氧基-4-甲基-2-硝基苯甲酰氯进行N-酰化，得到合成5,5'-甲基丙氨酸放线菌素D中的一种已知中间体。该方法构成了一条合成放线菌素以及潜在地合成其他肽内酯抗生素的新颖合成路线。
