title: 2-Pyridinyl Thermolabile Groups as General Protectants for Hydroxyl, Phosphate, and Carboxyl Functions.
abstract: 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.
authors.affiliation: Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznań, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Brzezinska
authors.affiliation: Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Witkowska
authors.affiliation: Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznań, Poland.
authors.forename: Tomasz P
authors.initials: TP
authors.lastname: Kaczyński
authors.affiliation: Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznań, Poland.
authors.forename: Dominika
authors.initials: D
authors.lastname: Krygier
authors.affiliation: Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznań, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Ratajczak
authors.affiliation: Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznań, Poland.
authors.forename: Marcin K
authors.initials: MK
authors.lastname: Chmielewski
mesh_terms: D001671:Biochemistry / Q000379:methods*; D002254:Carbonates / Q000138:chemical synthesis*; D003500:Cyclization; D017665:Hydroxyl Radical; D009705:Nucleosides / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry*
chemical_list: D002254:Carbonates; D009705:Nucleosides; D010710:Phosphates; D011725:Pyridines; D017665:Hydroxyl Radical; C023666:pyridine
keywords: chemical switch; intramolecular cyclisation; nucleosides; protecting groups; thermal lability; “click-clack”