Tailored Approaches towards the Synthesis of L-S-(Trifluoromethyl)cysteine- and L-Trifluoromethionine-Containing Peptides
Tailored Approaches towards the Synthesis of L-S-(Trifluoromethyl)cysteine- and L-Trifluoromethionine-Containing Peptides
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DOI：
10.1002/ejoc.201601318
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发表时间：
2017-01-10
影响因子：
2.8
通讯作者：
Brigaud, Thierry
中科院分区：
文献类型：
--
作者：
Gadais, Charlene;Saraiva-Rosa, Nathalie;Brigaud, Thierry
在氟化的非规范氨基酸中，1-三氟甲硫氨酸（TFM）和1-S-（三氟甲基）半胱氨酸（TfmCys），甲硫氨酸和半胱氨酸的氟化类似物，由于其局部增加肽的疏水性的能力而特别令人感兴趣。我们在此报告的叔丁氧羰基/苄基保护的TFM和TfmCys的合成通过使用廉价和用户友好的自由基三氟甲基化的方法。这些含氟氨基酸的苄基保护基可以通过氢解方便地除去，从而避免了麻烦的皂化反应。首次通过液相或固相肽合成将TfmCys插入肽序列中。最后，在二硫键桥接肽上使用Togni试剂的晚期三氟甲基化策略也有效地将TFM或TfmCys掺入N-末端和内部位置。
Among the fluorinated noncanonical amino acids, l-trifluoromethionine (TFM) and l-S-(trifluoromethyl)cysteine (TfmCys), fluorinated analogues of methionine and cysteine, are of particular interest because of their ability to locally increase the hydrophobicity of peptides. We report herein the synthesis of tert-butoxycarbonyl/benzyl-protected TFM and TfmCys by using a cheap and user-friendly radical trifluoromethylation approach. The benzyl protecting group of these fluorinated amino acids could be conveniently removed by hydrogenolysis, which circumvented troublesome saponification reactions. For the first time, TfmCys was inserted into a peptide sequence by liquid- or solid-phase peptide synthesis. Finally, a late trifluoromethylation strategy with the use of Togni's reagent on disulfide-bridged peptides was also efficient to incorporate TFM or TfmCys at both N-terminal and internal positions.