Comparative study of methods to couple hindered peptides.
Comparative study of methods to couple hindered peptides.
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受阻肽偶联方法的比较研究。
DOI：
10.1111/j.1399-3011.1992.tb00303.x
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Goodman,M
中科院分区：
文献类型：
--
作者：
Spencer,JR;Antonenko,VV;Delaet,NG;Goodman,M
对Boc保护的氨基酸衍生物与N-末端α，α-二烷基化和N-甲基化二肽的现代偶联反应进行了比较研究。使用等摩尔量的氨基和活化的羧基组分或过量的活化的羧基组分进行偶联反应。比较目标三肽Boc-Phe-Xaa-Phe-OBzl（Xaa =（NMe）Ala、（NMe）Alb或（NMe）α Ac 5c）的产率。当Xaa =（NMe）Aib和（NMe）α cAc 5c时，从利用新戊酰基混合酸酐、五氟苯基酯或酰氟活化的方法获得小于10%的产物。在室温下，从使用过量HBTU试剂（O-苯并三唑-1-基-N，N，N′，N′-四甲基脲鎓六氟磷酸盐）、PyBroP试剂（溴-三-吡咯烷基-鏻六氟磷酸盐）或Boc-Phe-NCA（Boc-保护的苯丙氨酸N-羧酸酐）的反应中获得了这两种产物的显著产率。此外，当在延长的反应时间内或在升高的温度下使用时，Boc-Phe-NCA方法是上级的。
A comparative study of modern coupling reactions involving Boc‐protected amino acid derivatives and dipeptides withN‐terminal α,α–dialkylation andN‐methylation was carried out. The coupling reactions were run using either equimolar amounts of the amino and activated carboxyl components or an excess of the activated carboxyl component. Yields of the target tripeptide Boc‐Phe‐Xaa‐Phe‐OBzl (Xaa = (NMe)Ala, (NMe)Alb, or (NMe)αAc5c) were compared. Less than 10% of the product was obtained from methods utilizing pivaloyl mixed anhydride, pentafluorophenyl ester or acyl fluoride activation when Xaa = (NMe)Aib and (NMe)αcAc5c. At room temperature, significant yields of these two products were obtained from reactions which utilized an excess of the HBTU reagent (O‐benzotriazol‐1‐yl‐N,N,N′,N′‐tetramethyluronium hexafluorophosphate), the PyBroP reagent (bromo‐tris‐pyrrolidino‐phosphonium hexafluorophosphate) or Boc‐Phe‐NCA (Boc‐protected phenylalanineN‐carboxyanhydride). Moreover, the Boc‐Phe‐NCA method was superior when used over a prolonged reaction time or at elevated temperature.