Brzezinska Jolanta, Witkowska Agnieszka, Kaczyński Tomasz P, Krygier Dominika, Ratajczak Tomasz, Chmielewski Marcin K
Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznań, Poland.
Curr Protoc Nucleic Acid Chem. 2017 Mar 2;68:2.20.1-2.20.25. doi: 10.1002/cpnc.26.
Application of 2-pyridinyl thermolabile protecting groups (2-PyTPGs) for protection of hydroxyl, phosphate, and carboxyl functions is presented in this unit. Their characteristic feature is a unique removal process following the intramolecular cyclization mechanism and induced only by temperature rise. Deprotection rate of 2-PyTPGs is dependent on certain parameters, such as solvent (aqueous or non-aqueous medium), pH values, and electron distribution in a pyridine ring. The presented approach pertains not only to protecting groups but also to an advanced system of controlling certain properties of 2-pyridinyl derivatives. We improved the "chemical switch" method, allowing us to regulate the protecting group stability by inversing the electron distribution in 2-PyTPG. Together with pH values manipulation, this allows us to regulate the protecting group stability. Moreover, phosphite cyclization to oxazaphospholidine provides a very stable but easily reversible tool for phosphate protection/modifications. For all TPGs we confirmed their utility in a system of protecting groups. This concept can contribute to designing the general protecting group that could be useful in bioorganic chemistry. © 2017 by John Wiley & Sons, Inc.
本单元介绍了2-吡啶基热不稳定保护基团（2-PyTPGs）在保护羟基、磷酸基和羧基官能团方面的应用。它们的特点是遵循分子内环化机制且仅由温度升高诱导的独特去除过程。2-PyTPGs的脱保护速率取决于某些参数，如溶剂（水性或非水性介质）、pH值以及吡啶环中的电子分布。所提出的方法不仅适用于保护基团，还适用于控制2-吡啶基衍生物某些性质的先进体系。我们改进了“化学开关”方法，通过反转2-PyTPG中的电子分布来调节保护基团的稳定性。结合pH值的调控，这使我们能够调节保护基团的稳定性。此外，亚磷酸环化生成恶唑磷烷为磷酸保护/修饰提供了一种非常稳定但易于可逆的工具。对于所有TPGs，我们证实了它们在保护基团体系中的实用性。这一概念有助于设计在生物有机化学中可能有用的通用保护基团。© 2017约翰威立国际出版公司。
