Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Aug 16;89(16):11272-11280.
doi: 10.1021/acs.joc.4c00944. Epub 2024 Aug 1.

Synthesis of Selenium-Decorated N-Oxide Isoquinolines: Arylseleninic Acids in Selenocyclization Reactions

João M Anghinoni  1 , Sabrina S Ferreira  1 , Jean C Kazmierczak  2 , Gelson Perin  1 , Filipe Penteado  2 , Eder J Lenardão  1
Affiliations

Synthesis of Selenium-Decorated N-Oxide Isoquinolines: Arylseleninic Acids in Selenocyclization Reactions

João M Anghinoni et al. J Org Chem. .

Abstract

Herein, we describe the use of benzeneseleninic acid derivatives (BSA) as a bench-stable and easy to handle selenium reagent to access 4-(selanyl)isoquinoline-N-oxides through the selenocyclization of o-alkynyl benzaldehyde oximes. The reaction is conducted in refluxing methanol, allowing the thermal generation of electrophilic selenium species in situ. By this new protocol, a library of 19 selenium-decorated N-oxide isoquinolines was accessed in up to 96% yield with an outstanding substrate tolerance and the feasibility to scale it up 10 times (from 0.25 to 2.5 mmol).

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Bioactive N-based heterocycles, and synthetic strategies to prepare N-oxide isoquinolines.
Scheme 1
Scheme 1. Synthetic Approach for the Synthesis of Se-Decorated N-Oxide Isoquinolines
Scheme 2
Scheme 2. Scale-up Experiments and Synthetic Applications of 3a
Scheme 3
Scheme 3. Control Experiments and Plausible Mechanism
See this image and copyright information in PMC

References

    1. Eicher T.; Hauptamann S.; Speicher A.. The Chemistry of Heterocycles: Structures, Reactions, Synthesis, and Applications, 3rd ed., Completely Revised and Enlarged; Wiley-VCH: Weinheim, 2012.
    2. Li J. J.Heterocyclic Chemistry in Drug Discovery; Wiley-VCH: Winheim, 2013.
    3. Taylor A. P.; Robinson R. P.; Fobian Y. M.; Blakemore D. C.; Jones L. H.; Fadeyi O. Modern Advances in Heterocyclic Chemistry in Drug Discovery. Org. Biomol. Chem. 2016, 14, 6611–6637. 10.1039/C6OB00936K. - DOI - PubMed
    4. Quin L. D.; Tyrell J. A.. Fundamentals of Heterocyclic Chemistry; Wiley-VCH: Weinheim, 2010.
    5. Katritzky A. R.; Rees C. W.. Comprehensive Heterocyclic Chemistry; Pergamon Press: Oxford, 1984.
    6. Katritzky A. R.; Rees C. W.; Scriven E. F. V.. Comprehensive Heterocyclic Chemistry II; Pergamon Press: Oxford, 1996.
    7. Katritzky A. R.; Rees C. W.; Scriven E. F. V.. Comprehensive Heterocyclic Chemistry III; Pergamon Press: Oxford, 1999.
    1. Vardanyan R.; Hruby V.. Synthesis of Best-Seller Drugs; Academic Press: London, 2016.
    2. Heravi M. M.; Zadsirjan V. Prescribed Drugs Containing Nitrogen Heterocycles: An Overview. RSC Adv. 2020, 10, 44247–44311. 10.1039/D0RA09198G. - DOI - PMC - PubMed
    3. Kumari S.; Maddeboina K.; Bachu R. D.; Boddu S. H. S.; Trippier P. C.; Tiwari A. K. Pivotal Role of Nitrogen Heterocycles in Alzheimer’s Disease Drug Discovery. Drug Discovery Today 2022, 27, 103322. 10.1016/j.drudis.2022.07.007. - DOI - PubMed
    4. Vitaku E.; Smith D. T.; Njardarson J. T. Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among US FDA Approved Pharmaceuticals: Miniperspective. J. Med. Chem. 2014, 57, 10257–10274. 10.1021/jm501100b. - DOI - PubMed
    5. Taylor R. D.; MacCoss M.; Lawson A. D. G. Rings in Drugs. J. Med. Chem. 2014, 57 (14), 5845–5859. 10.1021/jm4017625. - DOI - PubMed
    1. Speight T. M.; Brogden R. N.; Avery G. S. Cephalexin: A Review of its Antibacterial, Pharmacological and Therapeutic Properties. Drugs 1972, 3, 9–78. 10.2165/00003495-197203010-00002. - DOI - PubMed
    2. Harrison C. J. D.; Bratcher D. Cephalosporins: A Review. Pediatr. Rev. 2008, 29, 264–273. 10.1542/pir.29-8-264. - DOI - PubMed
    1. Becker H. A.; Schölkens B. Ramipril: Review of Pharmacology. Am. J. Cardiol. 1987, 59, D3–D5. 10.1016/0002-9149(87)90045-2. - DOI - PubMed
    2. Frampton J. E.; Peters D. H. Ramipril: An Updated Review of Its Therapeutic Use in Essential Hypertension and Heart Failure. Drugs 1995, 49, 440–466. 10.2165/00003495-199549030-00008. - DOI - PubMed
    3. Todd P. A.; Benfield P. Ramipril: A Review of Its Pharmacological Properties and Therapeutic Efficacy in Cardiovascular Disorders. Drugs 1990, 39, 110–151. 10.2165/00003495-199039010-00009. - DOI - PubMed
    4. Warner G. T.; Perry C. M. Ramipril: A Review of its Use in the Prevention of Cardiovascular Outcomes. Drugs 2002, 62, 1381–1410. 10.2165/00003495-200262090-00016. - DOI - PubMed
    1. O’Brien J. J.; Campoli-Richards D. M. Acyclovir: An Updated Review of Its Antiviral Activity, Pharmacokinetic Properties, and Therapeutic Efficacy. Drugs 1989, 37, 233–309. 10.2165/00003495-198937030-00002. - DOI - PubMed
    2. Ormrod D.; Goa K. Valaciclovir: A Review of its Use in the Management of Herpes Zoster. Drugs 2000, 59, 1317–1354. 10.2165/00003495-200059060-00009. - DOI - PubMed
    3. Richards D. M.; Carmine A. A.; Brogden R. N.; Heel R. C.; Speight T. M.; Avery G. S. Acyclovir: A Review of Its Pharmacodynamic Properties and Therapeutic Efficacy. Drugs 1983, 26, 378–408. 10.2165/00003495-198326050-00002. - DOI - PubMed
    4. Ormrod D.; Scott L. J.; Perry C. M. Valaciclovir: A Review of its Long-Term Utility in the Management of Genital Herpes Simplex Virus and Cytomegalovirus Infections. Drugs 2000, 59, 839–863. 10.2165/00003495-200059040-00013. - DOI - PubMed
    5. Skevaki C. L.; Galani I. E.; Pararas M. V.; Giannopoulou K. P.; Tsakris A. Treatment of Viral Conjunctivitis with Antiviral Drugs. Drugs 2011, 71, 331–347. 10.2165/11585330-000000000-00000. - DOI - PubMed

LinkOut - more resources