A novel and effective method is presented for modulating the stability of 2-Pyridinyl Thermolabile Protecting Groups (2-Py TPGs) in the "chemical switch" approach. The main advantage of the discussed approach is the possibility of changing the nucleophilic character of pyridine nitrogen using different switchable factors, which results in an increase or decrease in the thermal deprotection rate. One of the factors is transformation of a nitro into an amine group via reduction with a low-valent titanium in mild conditions. The usefulness of our approach is corroborated using 3'-O-acetyl nucleosides as model compounds. Their stability in various solvents and temperatures before and after reduction is also examined. Pyridine N-oxide and pH are other factors responsible for the nucleophilicity and stability of 2-Pyridinyl Thermolabile Protecting Groups in thermal deprotection. Protonation of 4-amino 2-Pyridinyl Thermolabile Protecting Groups is demonstrated by (1)H-(15)N HMBC and HSQC NMR analysis.
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.
Due to the increasing prevalence of neoplasms, there is a permanent need for new selective cytostatic compounds. Anticancer drugs can act in different ways, affecting protein expression and synthesis, including disruption of signaling pathways within cells. Continuing our previous research aiming at elucidating the mechanism of pyrazole’s anticancer activity, we carried out in silico studies on the interactions of fused pyrazole derivative with alanine, lysine, glutamic acid, and methionine. The objective of the study is to improve our understanding of the possible interactions of pyrazole derivatives with the above-mentioned amino acids. For this purpose, we apply the DFT formalism (optimization using the B3LYP, CAM-B3LYP, PBE0, and M06L functionals) and interaction energy calculations (counterpoise corrected method based on the basis set superposition error, BSSE) together with QTAIM approach and estimation of the 1H NMR chemical shifts of analyzed pyrazole derivative using different basis sets and DFT functionals in CPCM solvation model (and water used as a solvent).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.