Synthesis of 2-aryl Pyrroles, Prodigiosene F-BODIPYs and B-ring Modified Prodigiosenes

Abstract

Pyrrole constitutes the structural backbone of many natural products including heme and prodigiosin. This tripyrrolic natural product, and its synthetic analogues termed prodigiosenes, are reported to have an impressive array of biological activities including but not limited to immunosuppressive, antimalarial, anticancer, and antimicrobial effects. While the anticancer properties of these compounds are well known, the exact mechanism by which they impart such activity is unclear. When prodigiosene is protonated, is becomes an excellent ion transporter, and one proposed mechanism involves apoptosis of cancer cells induced via alteration of intracellular pH.

These tripyrrolic frameworks are not only effective at transporting ions, but also readily chelate to metals. When complexed with boron, a fluorescent dye known as a boron dipyrromethene (BODIPY) is formed. These dyes have attracted much attention due to their chemical robustness, large molar absorption coefficients, high fluorescence quantum yields and high photostability. These criteria are critical when developing dyes for fluorescence imaging and other biomedical applications. The work presented herein focuses on the synthesis of pyrrolic compounds, specifically 2-aryl pyrroles, prodigiosene F-BODIPYs, and B-ring modified prodigiosenes. The first project involved the synthesis of a series of prodigiosene F-BODIPYs with varying substitution on each of the pyrrolic rings. This published work was the first of its kind to study how varying substitution about the prodigiosene core affects the photophysical properties of the corresponding F-BODIPYs. The second project, also published work, focused on the synthesis of 2-aryl pyrroles via decarboxylative cross-coupling. The final project involved the total synthesis of a series of prodigiosenes modified with thioether functionality on the B-ring in efforts to enhance its biological activity. Previous work in the synthesis and study of prodigiosenes has involved modifications to the A-ring, B-ring and C-ring. However, there have been no reported studies focused on modifying the ether functionality on the B-ring, which is known to be responsible for much of the biological activity of prodigiosin.