Prodigiosin is the parent member of the 4-methoxypyrrolyldipyrromethene family of natural products and is known for its anti-cancer activity. A new series of analogues was synthesized, incorporating pendent functional esters and beta-carbonyl substituents on the C-ring. The beta-carbonyl group allowed for the facile isolation of the prodigiosenes, and the pendent esters allow for further derivatization. The novel prodigiosenes generally retain the anti-cancer activity of prodigiosin in 60 human cell lines derived from nine cancer cell types, with neither the conjugated beta-carbonyl group, as either ketone or ester, nor the pendent ester significantly reducing the anti-cancer activity of the core skeleton.

A new class of prodigiosenes with stability-enhancing functionalities appended to the C-ring were found to transport chloride anions through liposomal membranes, as well as to induce copper-mediated DNA cleavage.

m ic ro wa ve en er gyEt hylen e g lyco l, p -TS A m ic ro wa ve en er gyBenzyl 3,5-dimethyl-pyrrole-2-carboxylate, a very useful pyrrole in porphyrin and dipyrromethene synthesis, can be synthesized via the Knorr-type reaction, but in low yield. Alternative routes to benzyl 3,5-dimethyl-pyrrole-2-carboxylate have been developed involving the trans-esterification of ethyl 3,5-dimethyl-pyrrole-2-carboxylate and the de-acetylation of benzyl 4-acetyl-3,5-dimethyl-2-carboxylate, both precursors being easily obtained using the Knorr reaction. These traditional methods involve treatment of the known products with a strong basic solution or heating for extended periods which often lead to decomposition. The use of microwave energy to promote these two reactions proves to be an extremely efficient way to obtain benzyl 3,5-dimethyl-pyrrole-2-carboxylate quickly, in high yield, and in excellent purity with no need for recrystallization. Of particular note is the use of catalytic sodium methoxide in benzyl alcohol, rather than stoichiometric amounts of sodium benzoxide, to effect benzylation.

Pyrrole derivatives R 0120Microwave-Accelerated Synthesis of Benzyl 3,5-Dimethyl-pyrrole-2-carboxylate.-Microwave irradiation is used to accelerate transesterification and deacetylation reaction, resp., to the title compound (III). The optimization of the reaction conditions is discussed. -(REGOURD, J.; COMEAU, I. M.; BESHARA, C. S.; THOMPSON*, A.; J. Heterocycl. Chem. 43 (2006) 6, 1709-1714; Dep. Chem., Dalhousie Univ., Halifax, Nova Scotia B3H 4J3, Can.; Eng.) -H. Haber