title: Modeling of the Bioactivation of an Organic Nitrate by a Thiol to Form a Thionitrate Intermediate.
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.
authors.affiliation: Department of Chemistry, School of Science, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551, Japan. tsukasano8.24@gmail.com.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sano
authors.affiliation: Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. shimak@cronos.ocn.ne.jp.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Chemistry, School of Science, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551, Japan. organic_12_05@yahoo.co.jp.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. t.kawashima304@gmail.com.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kawashima
authors.affiliation: Department of Chemistry, School of Science, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551, Japan. ssase@chem.titech.ac.jp.
authors.forename: Shohei
authors.initials: S
authors.lastname: Sase
authors.affiliation: Department of Chemistry, School of Science, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8551, Japan. goto@chem.titech.ac.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Goto
mesh_terms: D000478:Alkylation; D001711:Biotransformation; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D007700:Kinetics; D008956:Models, Chemical; D009566:Nitrates / Q000138:chemical synthesis*; D009569:Nitric Oxide / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis*
chemical_list: D009566:Nitrates; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide
keywords: X-ray crystallographic analysis; biotransformation; kinetic stabilization; nitric oxide; organic nitrates; reactive intermediates; thionitrates