Initial steps on the synthesis of new antimicrobial fumiquinazoline related alkaloids

Currently drug resistance is rising to dangerously high levels worldwide and threatening our ability to treat even common infectious diseases. Secondary metabolites, especially alkaloids containing an indole group and structurally related to fumiquinazolines, can be found in both marine and terrestrial secondary metabolites and are of great importance in the area of drug discovery with promising antimicrobial properties.

This work aims to synthesize alkaloids related to fumiquinazolines, as well as introducing new molecular modifications, in order to improve their properties as antimicrobial agents.

The initial synthetic steps towards the total synthesis of fumiquinazoline F and glyantripine, as well as to two new compounds with fluorine substituents in the anthranilic acid moiety are described. A multi-step synthetic pathway was followed through conjugation of anthranilic acid, D-tryptophan methyl ester hydrochloride and the correspondent third amino acid (glycine or alanine). Structure elucidation by ¹H-NMR spectroscopy indicated that the obtained compounds correspond to the stablished structures. Future work will involve screening of the new alkaloids for their antibacterial activities.

Acknowledgments:

This research was supported by national funds through FCT - Foundation for Science and Technology within the scope of UIDB/04423/2020, UIDP/04423/2020 (Group of Natural Products and Medicinal Chemistry_CIIMAR), and under the project PTDC/SAU-PUB/28736/2017 (reference POCI-01-0145-FEDER-028736), co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF and by FCT through national funds, as well as CHIRALBIOACTIVE-PI-3RL-IINFACTS-2019. Mariana C. Almeida acknowledges the BYT+ scholarship to CIIMAR.