Towards the Synthesis of Di- and Tri-Pyrrolic Compounds

Abstract

Dipyrrins and prodigiosenes are two classes of pyrrolic compounds. Dipyrrins consist of two pyrrole units linked by a methane bridge and prodigiosenes are a class of pyrrolyldipyrrins (a dipyrrin with a pyrrole substituent) containing a methoxy substituent. During this graduate work, two projects were undertaken to investigate these two classes. The first project involved the development of a novel methodology for the synthesis of symmetric meso-H-dipyrrin hydrobromides. The reaction of 2-formylpyrroles in acidic methanol gives the corresponding symmetric, meso-H-dipyrrin hydrobromides in good yields. This convenient one-pot strategy involves initial deformylation under the acidic conditions, followed immediately by in situ reaction of the resulting α-free pyrrole with the remaining 2-formyl pyrrole in solution. However, there is evidence of some concerted character in this reaction mechanism and this is being investigated by isotopic labeling of a symmetric, α-free, 2-formyl pyrrole. The second project involves the synthesis of a series of prodigiosenes in order to study their biological activity with respect to anticancer activity and leukemia selectivity. Acute myeloid leukemia (AML) accounts for the majority of adult leukemias and remains fatal for 40% of patients. Recently published work presented four new prodigiosenes featuring alkanoate substitution patterns, the first of their kind to be developed in the Thompson lab and the first to exhibit strong selectivity against leukemia cell lines. As such, a series of twelve new prodigiosenes have been designed and synthesized to probe the role of the alkyl ester substituent, the role of the ester moiety versus an amide moiety, the role of lipophilicity and the necessity of an alkyl ester over a conjugated ester regarding cell line selectivity.