A General Route to 1,3′-Bipyrroles

Abstract

A general method is described for the synthesis of 1,3'-bipyrroles. The route involves constructing a pyrrole ring on the nitrogen of a substituted 1H-pyrrole, so as to generate the 1,3'-bipyrrole. In this approach the nitrogen of the starting pyrrole was alkylated with a special Michael acceptor having an allylic leaving group, and the product was then modified in such a way that the second pyrrole ring could be formed by a Paal-Knorr reaction. Two variants of this sequence were examined, one of which led to formation of a 3-hydroxypyridine instead of the second pyrrole ring; the other variant used phenacyl bromide instead of the special Michael acceptor.

Marinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bim

“…Due to their novel molecular structures and promising biological properties, marinopyrroles have attracted considerable attention [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16]. Following our finding that (±)-marinopyrrole A ( 1 ) antagonizes Mcl-1 and overcomes resistance of human cancer cells to the Bcl-xL antagonist ABT-737 [10], we recently reported a series of novel cyclic marinopyrroles as disruptors of protein-protein interactions between the pro-apoptotic protein, Bim, and the pro-survival proteins, Bcl-xL and Mcl-1 [16].…”

Enantioselective Synthesis of Pyrrolizin-1-ones via Lewis Base Catalyzed N-Allylation of N-Silyl Pyrrole Latent Nucleophiles

“…Electronically matched and mismatched sets of nucleophiles and electrophiles performed equally well in these reactions with generally good yields ( 8kc , 8if , 8wi , 8jl , 8om , 8xi ). Even sterically demanding nucleophiles/electrophiles, previously reported not to be reactive in related reactions, performed reasonably well with yields of around 50% ( 8bk and 8wi ) . The reactions proceeded with excellent regioselectivity: C2/C3 allylation of N-heterocycles and S N 2′ type products were not observed in any of the reactions.…”

“…Even sterically demanding nucleophiles/electrophiles, previously reported not to be reactive in related reactions, performed reasonably well with yields of around 50% (8bk and 8wi). 11 The reactions proceeded with excellent regioselectivity: C2/C3 allylation of N-heterocycles and S N 2′ type products were not observed in any of the reactions.…”

Crystallographic, spectroscopic and thermal studies of 1-(4-bromophenyl)-5-(2,5-dimethyl-1H-pyrrol-1-yl)-3-methyl-1H-pyrazole

“…Additionally, metal halides showed outstanding performance as Lewis acid catalysts in the Paal-Knorr reaction (Aghapoor et al, 2018;Rahmatpour, 2012;Zhang et al, 2008). Furthermore, a variety of Brønsted acid catalysts, such as acetic acid (Cheng et al, 2013), phosphoric acid (Zhang et al, 2017), sulfamic acid (Luo et al, 2008) and p-toluenesulfonic acid (Bharadwaj et al, 2004), among others, have been employed successfully. In this regard, Akelis et al (2016) described a solventless Paal-Knorr synthesis of N-substituted pyrroles in 15-84% yields by using mechanochemical activation at 30 Hz for 15-30 min in the presence of citric acid (1 mol%) as an organocatalyst.…”