SYNTHESIS OF INDOLE-BASED ALKALOIDS AND THEIR ANALOGUES
Pollák Patrik
Gyógyszertudományok és Egészségügyi Technológiák Tagozat
Dr. Zelkó Romána
SE Semmelweis Szalon
2026-05-21 10:00:00
Modern Trends in Pharmaceutical Scientific Research
Dr. Antal István
Dr. Milen Mátyás, Dr. Volk Balázs
Dr. Mátravölgyi Béla
Dr. Krajsovszky Gábor
Dr. Zelkó Romána
Dr. Dunkel Petra
Dr. Balogh Weiser Diána
This doctoral work describes the design, synthesis, and mechanistic study of indolederived
alkaloids and their synthetic analogues, combining classical and modern organic
chemistry with computational modeling and biological evaluation. The project was
inspired by the role of the indole scaffold in natural and synthetic bioactive compounds
and by the interest in developing alternative synthetic methodologies.
Novel oxazolyl- and thiazolylindoles were prepared through optimized Robinson–
Gabriel synthesis and thionation reactions, and their antiproliferative activities were
evaluated in vitro. The thiazolyl and carbothioamide derivatives exhibited the highest
activity and selectivity toward tumor cell lines. Enantioselective syntheses of
bacillamides B–D and neobacillamide A were then achieved using asymmetric transfer
hydrogenation and Mitsunobu reaction steps, with absolute configurations supported by
SC-XRD, providing the first structural elucidations within this group of alkaloids.
Further studies resulted in concise syntheses of orthoscuticelline B, brevicarine, and
brevicolline, including practical alternatives to earlier reported methods. The work also
applied flow-based approaches to the synthesis of 1-substituted 3,4-dihydro-β-carbolines,
exploring their synthetic scalability and easy operation. Complementary computational
investigations offered a possible rationale for the different mechanistic pathways and
energetic preferences of the key cyclization reactions, providing a theoretical framework
for the selectivities observed throughout the project.
Overall, the results of this dissertation present synthetic strategies, mechanistic
insights, and biological data related to the field of heterocyclic chemistry. The
methodologies and compounds developed herein could provide a basis for future research
aimed at the exploration of indole-based therapeutic agents.
