Efficient method of circumventing insolubility problems with fully protected peptide carboxylates via in situ direct thioesterification reactions
Efficient method of circumventing insolubility problems with fully protected peptide carboxylates via in situ direct thioesterification reactions
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DOI：
10.1002/psc.1181
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发表时间：
2009-11-01
影响因子：
2.1
通讯作者：
Flemer, Stevenson, Jr.
中科院分区：
文献类型：
--
作者：
Flemer, Stevenson, Jr.
提出了一种简单方便的方案，用于对通过 Fmoc 策略合成的完全保护的肽 C 末端羧酸盐进行直接硫酯化。该方法特别用于通过在新裂解的 1% TFA/DCM 羧酸酯溶液上进行原位反应来克服这些完全受保护的羧酸酯分离物在硫酯化过程中经常出现的不溶性问题。探索了许多易不溶的肽系统的直接硫酯化，并与一些对照系统进行比较，以便于转化为相应的硫酯。结果表明，尽管完全保护的羧酸盐在使用经典方法进行的硫酯化反应中确实不同程度地不溶，但使用原位方法可以保持完全溶解并且完全转化是明显的。该方案旨在消除通过直接方法制备肽硫酯时常见的绊脚石，从而可以轻松进入以前通过该方法传统上无法接近的困难系统。版权所有 (C) 2009 欧洲肽协会和 John Wiley & Sons, Ltd.
A straightforward and convenient protocol is presented for the direct thioesterification of fully protected peptide C-terminal carboxylates synthesized by Fmoc strategy. This methodology specifically serves to overcome the frequent insolubility problem of these fully protected carboxolate isolates during the thioesterification process by carrying out the reaction as an in situ procedure on the freshly cleaved 1% TFA/DCM solution of carboxylate. The direct thioesterification of a number of insolubility prone peptide systems is explored and compared with some control systems for ease of conversion to the corresponding thioesters. It is shown that although the fully protected carboxylates are indeed insoluble to varying degrees in the thioesterification reactions carried out using the classical approach,full dissolution is maintained and complete conversion is evident using the in situ methodology. This protocol serves to remove a frequent stumbling block in the preparation of peptide thioesters via the direct approach, allowing for facile entry into previously difficult systems traditionally unapproachable through this method. Copyright (C) 2009 European Peptide Society and John Wiley & Sons, Ltd.