Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation

Jim Secka; Arpan Pal; Francis A Acquah; Blaine H M Mooers; Anand B Karki; Dania Mahjoub; Mohamed K Fakhr; David R Wallace; Takuya Okada; Naoki Toyooka; Adama Kuta; Naga Koduri; Deacon Herndon; Kenneth P Roberts; Zhiguo Wang; Bethany Hileman; Nisha Rajagopal; Syed R Hussaini

doi:10.1039/d2ra02415b

Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation

RSC Adv. 2022 Jul 5;12(30):19431-19444. doi: 10.1039/d2ra02415b. eCollection 2022 Jun 29.

Authors

Jim Secka¹, Arpan Pal¹, Francis A Acquah^{2

3

4}, Blaine H M Mooers^{2

3

4}, Anand B Karki⁵, Dania Mahjoub⁵, Mohamed K Fakhr⁵, David R Wallace⁶, Takuya Okada⁷, Naoki Toyooka⁷, Adama Kuta¹, Naga Koduri¹, Deacon Herndon¹, Kenneth P Roberts¹, Zhiguo Wang¹, Bethany Hileman¹, Nisha Rajagopal¹, Syed R Hussaini¹

Affiliations

¹ Department of Chemistry and Biochemistry, The University of Tulsa 800 S. Tucker Drive Tulsa Oklahoma 74104 USA syed-hussaini@utulsa.edu.
² Department of Biochemistry and Molecular Biology, University of Oklahoma of Health Sciences Center Oklahoma City OK 73104 Unites States.
³ Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma Health Sciences Center Oklahoma City OK 73104 USA.
⁴ Laboratory of Biomolecular Structure and Function, University of Oklahoma of Health Sciences Center Oklahoma City OK 73104 USA.
⁵ Department of Biological Science, The University of Tulsa 800 S. Tucker Drive Tulsa Oklahoma 74104 USA.
⁶ Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences Tulsa Oklahoma 74107 USA.
⁷ Faculty of Engineering, University of Toyama 3190 Gofuku Toyama 930-8555 Japan.

Abstract

This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides. We plan to use this method to synthesize indolizidine (-)-237D analogs to find α6-selective antismoking agents. Therefore, we also performed in silico α6-nAchRs binding studies of selected products. Compounds with low root-mean-square deviation values showed more favorable binding free energies. We also report preliminary pharmacokinetic data on indolizidine (-)-237D and found it to have weak activity at CYP3A4. In addition, as enamino carbonyl compounds are also known for antimicrobial properties, we screened previously reported and new enamino carbonyl compounds for antibacterial, antimicrobial, and antifungal properties. Eleven compounds showed significant antimicrobial activities.

Abstract

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