Application of vinylogous carbamates and vinylogous aminonitriles to the regiospecific synthesis of uniquely functionalized pyrroles and quinolones

Abstract

Pyrroles and quinolones represent core structures, which are routinely found in both natural and synthetic bioactive substances. Consequently, the development of efficient and regiospecific methods for the preparation of such heterocycles with unique functionality is of some importance. We describe herein the regiospecific synthesis of 1,2,3,4-tetrasubstituted pyrroles containing polar substituents and such products are prepared from vinylogous carbamates and vinylogous aminonitriles. We also describe the regiospecific synthesis of 3-aryl containing 1,3,6trisubstituted quinolones from vinylogous carbamates. The use of an amine exchange reaction to prepare precursors for the pyrrole and quinolone forming cyclizations represents a key factor in the strategy.

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

“…This enaminone-based method for constructing a pyrrole ring is similar to that in our reported routes to lamellarin alkaloids, in which N-alkylation of ( Z )-configured 3,4-dihydroisoquinoline-derived enaminones with ethyl bromoacetate under either conventional [ 49 – 50 ] or microwave [ 51 ] heating conditions yielded pyrrolo[2,1- a ]isoquinoline products. A somewhat comparable cyclization of N -benzylenaminones has been reported under superbasic conditions [ 52 ], while base-induced pyrrole formation from N -(ethoxycarbonylmethyl)enamino esters (vinylogous urethanes) and the corresponding nitriles (vinylogous cyanamides) has also been described [ 53 ]. A similar base-induced cyclization of N -(alkoxycarbonylmethyl)-7-formylindoles to give pyrrolo[3,2,1- hi ]indoles is also of interest [ 54 ].…”

Synthesis, Antimicrobial and Antitumor Study of New Pyrido[2,1-a]isoquinolines via Isoquinoline-1-acetonitrile

“…26 Refluxing of the latter enaminonitrile 3 with 2-arylacetonitriles 2 in ethanol in the presence of piperidine yielded 4H-pyrido[2,1-a]-isoquinoline-1-carbonitrile derivatives 6a-d (Scheme 1). The latter products 6a-d were also prepared by treatment of enaminonitriles 4a-d 30,31 [prepared by refluxing of 2-arylacetonitriles 2 with N,N-dimethylformamide dimethyl acetal in dioxane] with 1 in refluxing ethanol in the presence of piperidine (Scheme 1).…”

“…The elemental analyses were performed at the Micro analytical center, Cairo University. The 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile 1,35 enaminonitrile 3,26 enaminonitrile 4a-d30,31 and ethyl 3-aryl-2-cyanoacrylate 9a-e32,33 were prepared using the reported procedures. In vitro antitumor activity was conducted at The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt.…”