1. Modeling of the Bioactivation of an Organic Nitrate by a Thiol to Form a Thionitrate Intermediate
- Author
-
Yohei Aoki, Shohei Sase, Tsukasa Sano, Kei Goto, Keiichi Shimada, and Takayuki Kawashima
- Subjects
Alkylation ,Pharmaceutical Science ,chemistry.chemical_element ,reactive intermediates ,Chemistry Techniques, Synthetic ,010402 general chemistry ,Crystallography, X-Ray ,Nitric Oxide ,01 natural sciences ,Analytical Chemistry ,lcsh:QD241-441 ,chemistry.chemical_compound ,Nitrate ,Biotransformation ,lcsh:Organic chemistry ,Drug Discovery ,Organic systems ,Organic chemistry ,Sulfhydryl Compounds ,Physical and Theoretical Chemistry ,kinetic stabilization ,Clinical treatment ,chemistry.chemical_classification ,organic nitrates ,Nitrates ,010405 organic chemistry ,Aryl ,Communication ,Organic Chemistry ,thionitrates ,0104 chemical sciences ,Organic nitrates ,Kinetics ,X-ray crystallographic analysis ,chemistry ,Models, Chemical ,Chemistry (miscellaneous) ,Thiol ,Molecular Medicine ,Lithium ,biotransformation - Abstract
Thionitrates (R-SNO₂) have been proposed as key intermediates in the biotransformation of organic nitrates that have been used for the clinical treatment of angina pectoris for over 100 years. It has been proposed and widely accepted that a thiol would react with an organic nitrate to afford a thionitrate intermediate. However, there has been no example of an experimental demonstration of this elementary chemical process in organic systems. Herein, we report that aryl- and primary-alkyl-substituted thionitrates were successfully synthesized by the reaction of the corresponding lithium thiolates with organic nitrates by taking advantage of cavity-shaped substituents. The structure of a primary-alkyl-substituted thionitrate was unambiguously established by X-ray crystallographic analysis.
- Published
- 2016