Synthesis of Boron-Based Natural Products as Anti-Cancer Agents

Overview

The overarching goal of this project is to synthesize effective, multicomponent anti-cancer compounds by coupling derivatives of boron and natural products. Benzoboroxoles, (cyclic boronic acids), are highly useful synthetic intermediates in drug design. Similarly, natural products have been the basis for development of many drugs. Betulin in particular is a natural product found in the bark of birch trees. This is the first ever study to couple a benzoboroxole and betulinic acid by using a triazole linker to make new, soluble, and potent anti-cancer compounds. Specifically, a benzoboroxole was synthesized through the Baylis-Hillman reaction. Betulinic acid was synthesized from betulin using Jones Oxidation. Next, an alkyne of the benzoboroxole (Intermediate 1) and an azide of betulinic acid (Intermediate 2) were generated. In the final step, a triazole, was used to connect Intermediates 1 and 2 together. The final aggregate molecule demonstrated the highest solubility in water and potency as evaluated in-vitro on human pancreatic cancer cell-lines(IC50 value of 7μm). This novel method is promising as a template for early-stage drug discovery, and research will continue to achieve potencies in the nano-molar concentrations required to make drugs for humans.