Investigation of Pharmaceutical Importance of 2H-Pyran-2-One Analogues via Computational Approaches

Symmetry

Samata E. Shetgaonkar¹  Fateh V Singh¹  Chandan Shivamallu²  Abdallah M. Elgorban³  Ali H. Bahkali³  Asad Syed³  Sanja J. Armaković⁴  Raghavendra G. Amachawadi⁵  Stevan Armaković⁶  Renjith Raveendran Pillai⁷  Shiva Prasad Kollur⁸  Karthick Thangavel⁹ 

[1] Chemistry Division, Chennai Campus, School of Advanced Science, VIT University, Chennai 600127, Tamil Nadu, India;Department of Biotechnology and Bioinformatics, School of Life Sciences, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India;Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia;Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D, Obradovića 3, 21000 Novi Sad, Serbia;Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506-5606, USA;Department of Physics, Faculty of Sciences, University of Novi Sad, Trg D, Obradovića 4, 21000 Novi Sad, Serbia;Department of Physics, T.K.M. College of Arts and Science, Karicode, Kollam 691005, Kerala, India;Department of Sciences, Amrita Vishwa Vidyapeetham, Mysuru Campus, Amrita School of Arts and Sciences, Mysuru 570026, Karnataka, India;School of Electrical & Electronics Engineering, SASTRA Deemed University, Tirumalaisamudram, Thanjavur 613401, Tamil Nadu, India;

关键词: tetralone;    DFT calculations;    MD simulations;    MEP;    bond dissociation;   

DOI  :  10.3390/sym13091619

来源: DOAJ

【 摘 要 】

Highly functionalized spirocyclic ketals were synthesized through asymmetric oxidative spirocyclization via carbanion-induced ring transformation of 2H-pyran-2-ones with 1,4-cyclohexandione monoethyleneketal under alkaline conditions. Further acidic-hydrolysis of obtained spirocyclic ketals yields highly substituted 2-tetralone in good yield. Computational analysis based on the DFT calculations and MD simulations has been performed in order to predict and understand global and local reactivity properties of newly synthesized derivatives. DFT calculations covered fundamental reactivity descriptors such as molecular electrostatic potential and average local ionization energies. Nitrogen atom and benzene rings have been recognized as the most important molecular sites from these aspects. Additionally, to predict whether studied compounds are stable towards the autoxidation mechanism, we have also studied the bond dissociation energies for hydrogen abstraction and identified the derivative which might form potentially genotoxic impurities. Interactions with water, including both global and local aspects, have been covered thanks to the MD simulations and calculations of interaction energies with water, counting of formed hydrogen interactions, and radial distribution functions. MD simulations were also used to identify which excipient could be used together with these compounds, and it has been established that the polyvinylpyrrolidone polymer could be highly compatible with these compounds, from the aspect of calculated solubility parameters.

【 授权许可】

Unknown