An Efficient Synthesis of 3-Alkylpyridine Alkaloids Enables Their Biological Evaluation

• Authors: Anna R Kaplan, Emory University; Cassandra L Schrank, Emory University; William Wuest, Emory University
• Journal Title: CHEMMEDCHEM
• Volume: Volume 16, Number 16
• Publisher: WILEY-V C H VERLAG GMBH | 2021-04-14, Pages 2487-2490
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/cmdc.202100134
• Subjects: Chemistry, General
• Keywords: Science & Technology; Life Sciences & Biomedicine; Chemistry, Medicinal; Pharmacology & Pharmacy; antimicrobial; haliclocyclins; hydroarylation; MRSA; quaternary ammonium compounds

Abstract

3-Alkylpyridine alkaloids (3-APAs) isolated from the arctic sponge Haliclona viscosa are a promising group of bioactive marine alkaloids. However, due to limited bioavailability, investigations of their bioactivity have been hampered. Additionally, synthesis of a common intermediate requires the use of protecting groups and harsh conditions. In this work, we developed a simple and concise two-step route to nine different natural and synthetic haliclocyclins. These compounds displayed modest antibiotic activity against several Gram-positive bacterial strains.