N -Methylation of Self-Immolative Thiocarbamates Provides Insights into the Mechanism of Carbonyl Sulfide Release.

Autor: Levinn CM; Department of Chemistry and Biochemistry, Materials Science Institute, Knight Campus for Accelerating Scientific Impact, Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, United States., Mancuso JL; Department of Chemistry and Biochemistry, Materials Science Institute, Knight Campus for Accelerating Scientific Impact, Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, United States., Lutz RE; Department of Chemistry and Biochemistry, Materials Science Institute, Knight Campus for Accelerating Scientific Impact, Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, United States., Smith HM; Department of Chemistry and Biochemistry, Materials Science Institute, Knight Campus for Accelerating Scientific Impact, Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, United States., Hendon CH; Department of Chemistry and Biochemistry, Materials Science Institute, Knight Campus for Accelerating Scientific Impact, Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, United States., Pluth MD; Department of Chemistry and Biochemistry, Materials Science Institute, Knight Campus for Accelerating Scientific Impact, Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, United States.
Jazyk: angličtina
Zdroj: The Journal of organic chemistry [J Org Chem] 2021 Apr 16; Vol. 86 (8), pp. 5443-5451. Date of Electronic Publication: 2021 Apr 05.
DOI: 10.1021/acs.joc.0c02778
Abstrakt: Hydrogen sulfide (H 2 S) is an important biomolecule, and self-immolative thiocarbamates have shown great promise as triggerable H 2 S donors with suitable analogous control compounds; however, thiocarbamates with electron-deficient payloads are less efficient H 2 S donors. We report here the synthesis and study of a series of N -methylated esterase-triggered thiocarbamates that block the postulated unproductive deprotonation-based pathway for these compounds. The relative reaction profiles for H 2 S release across a series of electron-rich and electron-poor N-Me aniline payloads are examined experimentally and computationally. We show that thiocarbamate N -methylation does block some side reactivity and increases the H 2 S release profiles for electron-poor donors. Additionally, we show that isothiocyanate release is not a competitive pathway, and rather that the reduced efficiency of electron-poor donors is likely due to other side reactions.
Databáze: MEDLINE
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