Skwarczynski Mariusz, Kiso Yoshiaki
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto, Japan.
Curr Med Chem. 2007;14(26):2813-23. doi: 10.2174/092986707782360123.
The O-N intramolecular acyl migration, also named as an acyl shift or acyl transfer reaction, is well-known in organic and peptide chemistry as a simple rearrangement which proceeds under very mild aqueous conditions. Despite a long history with this reaction, its application in medicinal chemistry has only lately been proposed. In the last decade, this reaction has been intensively studied and several applications of this rearrangement in medicinal chemistry have appeared. O-N Intramolecular acyl migration has been employed in "no auxiliary, no byproduct" prodrug strategies (prodrugs of paclitaxel and other taxoids, prodrugs of HIV protease inhibitors), for the synthesis of peptides containing difficult sequences via "O-acyl isopeptide method", including Alzheimer's disease related amyloid beta peptide (Abeta) 1-42, and in the design of pH-, photo- or enzyme-triggered click peptides, as a potential powerful tool for identifying the pathological functions of amyloid beta peptides in Alzheimer's disease. This review summarized recent advances in the application of O-N intramolecular acyl migration with special focus on medicinal chemistry.
O-N分子内酰基迁移，也被称为酰基转移或酰基转移反应，在有机化学和肽化学中是一种广为人知的简单重排反应，它能在非常温和的水性条件下进行。尽管该反应历史悠久，但其在药物化学中的应用直到最近才被提出。在过去十年中，人们对该反应进行了深入研究，并出现了这种重排在药物化学中的一些应用。O-N分子内酰基迁移已被用于“无辅助、无副产物”的前药策略（紫杉醇和其他紫杉烷类的前药、HIV蛋白酶抑制剂的前药），通过“O-酰基异肽法”合成含有困难序列的肽，包括与阿尔茨海默病相关的淀粉样β肽（Aβ）1-42，以及在pH、光或酶触发的点击肽的设计中，作为识别阿尔茨海默病中淀粉样β肽病理功能的一种潜在有力工具。本文综述了O-N分子内酰基迁移应用的最新进展，特别关注药物化学领域。
