Propylphosphonic Anhydride (T3P®) as Coupling Reagent for Solid-Phase Peptide Synthesis
Propylphosphonic Anhydride (T3P®) as Coupling Reagent for Solid-Phase Peptide Synthesis
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DOI：
10.1002/slct.202100123
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发表时间：
2021-02-16
期刊：
影响因子：
2.1
通讯作者：
Albericio, Fernando
中科院分区：
文献类型：
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作者：
Al Musaimi, Othman;Wisdom, Richard;Albericio, Fernando
酰胺化是制药环境中的主要反应，并且由于对治疗肽的需求增加，它正吸引更多的关注。肽的高治疗功效和安全性特征已经将这些分子置于药物竞技场内的主要位置，这反映在这些分子每年从各种管理机构获得若干批准。在这种情况下，对开发用于肽合成的有效策略的需求也有所上升。丙基膦酸酐（T3P（R））是一种新型的绿色偶联试剂，在溶液中表现出良好的偶联性能，但在固相肽合成（SPPS）中还没有应用。在这里，我们测试T3P（R）用于SPPS。采用温和的活化方案获得了令人满意的产率。测试了各种绿色溶剂，并证明与该偶联剂相容。几种常用试剂会引起过敏反应，或在某些条件下容易爆炸。为了克服这些问题，我们提出T3P（R）作为SPPS中潜在的替代偶联试剂。
Amidation is the predominant reaction within the pharmaceutical setting, and it is attracting greater attention due to the increased demand for therapeutic peptides. The high therapeutic efficacy and safety profile of peptides have placed these molecules in prime position within the pharmaceutical arena, which is reflected by these molecules receiving several approvals from various regulatory agencies each year. In this context, the demand for developing efficient strategies for peptide synthesis has also risen. Although propylphosphonic anhydride (T3P (R)), which has been recently proposed as a green coupling reagent, has shown good performance in solution, it has never been applied to solid-phase peptide synthesis (SPPS). Here we test the use of T3P (R) for SPPS. Satisfactory yields were achieved with a mild activation protocol. Various green solvents were tested and proved to be compatible with this coupling reagent. Several commonly used reagents cause allergic reactions or are susceptible to explosion under certain conditions. To overcome these issues, we propose T3P (R) as a potential alternative coupling reagent in SPPS.