Novel Synthetic Methodology and Total Syntheses of Highly Functionalized Carbazoles and Benzo[c]cinnolines

Abstract

This dissertation discloses a project encompassing a synthetic strategies and new methods for the synthesis of some functionalized N-heterocyclic compounds. Much attention have been focused to synthesize N-heterocyclic compounds due to their interesting biological properties in medicinal chemistry. Among the various Nheterocycles, carbazole and its derivatives are frequently embedded in numerous natural products and active pharmaceutical ingredients in various drug structures. In this thesis, carbazomycin G, a carbazole alkaloid owns a special interest due to their versatile biological properties. We have developed a methodology for the synthesis of carbazomycin G through 12-steps involving several new method development for the key intermediates via Suzuki cross coupling, indium reduction and especially Pdcatalyzed intramolecular ring closing reaction to obtain the carbazole moiety. Furthermore, we have developed a methodology to synthesize few particular Nheterocyclic compounds such as benzo[c]cinnoline and Boscalid® due to their attractive biological features and their applications in medicinal chemistry. Benzo[c]cinnoline and its derivatives are known for their various pharmacological activities and particularly anticancer property. The synthesis consists of two steps involving Suzuki cross coupling reaction followed by a redox process that leads to cyclic compound benzo[c]cinnoline. Another notable compound Boscalid® that is an important class of fungicide synthesized by means of three optimized steps and often applied to protect the agricultural crops. Moreover, a high rate and new reduction method based on sodium borohydride and cobalt sulfate was developed and optimized for the reduction of various reducible functional groups. The outline of the thesis including different synthetic strategies and new methodologies are summarized in graphical abstract.