Journal Article

Asymmetric synthesis and study of biological activity of (epi-)benzoanalogues of bioactive phenanthroquinolizidine alkaloids

Nováková, Eva, Sivý, Július, Pagáč, Tomáš, Šafář, Peter, Šupolíková, Miroslava, Kubíčková, Jana, Balónová, Barbora, Marchalín, Štefan, Šoral, Michal, Ježíková, Zuzana, Olejníková, Petra

2018

Overview

The increasing microbial resistance to primary active structures remains alarming and the effort to look for new antibacterial active structures is still of scientific interest. One of the attractive ways to find new active structures is derivatization of well-known natural compounds. Alkaloids are a structurally diverse group of natural products with a wide range of biological effects. Historically, an attempt to increase the antimicrobial activity of alkaloids through chemical modifications has been successful. In this work, 12 new quinolizidine derivatives were synthesized and tested for their antimicrobial activity. The asymmetric synthesis of the benzoanalogue of the phenanthroquinolizidine bioactive alkaloid (−)-cryptopleurine and the epi-benzoanalogues of (−)-(15 R )-hydroxycryptopleurine were achieved in six or seven steps starting from available enantiopure ( S )-2-aminoadipic acid used as source of chirality as well as nitrogen. The highest antimicrobial activity was observed in the presence of the final saturated structure, the benzoanalogue of naturally occurring plant alkaloid cryptopleurine. It features selective toxicity, and significantly inhibits the growth of G + bacteria, especially Staphylococcus sp. Tested derivatives have shown only a weak antifungal activity, but partial inhibition has been observed in the case of model yeasts. Graphical abstract

• Publisher: Springer Vienna,Springer Nature B.V
• Subject: Alcohol / Alkaloids / Analytical Chemistry / Antifungal activity / Antiinfectives and antibacterials / Antimicrobial activity / Antimicrobial agents / Asymmetric synthesis / Asymmetry / Bacteria / Biocompatibility / Biofilms / Biological activity / Biological effects / Chemical activity / Chemistry / Chemistry and Materials Science / Chemistry/Food Science / Chirality / Cytotoxicity / Derivatives / E coli / Fungicides / Gram-positive bacteria / Inorganic Chemistry / Microorganisms / Natural products / Organic Chemistry / Original Paper / Physical Chemistry / Single crystals / Staphylococcus infections / Synthesis / Theoretical and Computational Chemistry / Toxicity