Alexander N. Smirnov

Metal-free transannulation reaction of indoles with nitrostyrenes: a simple practical synthesis of 3-substituted 2-quinolones.

3-Substituted 2-quinolones are obtained via a novel, metal-free transannulation reaction of 2-substituted indoles with 2-nitroalkenes in polyphosphoric acid. The reaction can be used in conjunction with the Fisher indole synthesis offering a practical three-component heteroannulation methodology to produce 2-quinolones from arylhydrazines, 2-nitroalkenes and acetophenone.

Metal-free ring expansion of indoles with nitroalkenes: a simple, modular approach to 3-substituted 2-quinolones

3-Substituted 2-quinolones are obtained via a novel metal-free transannulation reaction of 2-nitroolefins with 2-substituted indoles in polyphosphoric acid. This acid-mediated cascade transformation operates via the ANRORC (Addition of Nucleophile, Ring Opening, and Ring Closure) mechanism and can be used in combination with the Fisher indole synthesis to offer a practical three-component hetero-annulation approach to 2-quinolones from arylhydrazines, 2-nitroalkenes, and acetophenone. An alternative entry to this chemistry employing the alkylation of electron-rich arenes and hetarenes with 1-(2-indolyl)-2-nitroalkene has also been demonstrated.

Activity of 2-aryl-2-(3-indolyl)acetohydroxamates against drug-resistant cancer cells.

Many types of tumor, including glioma, melanoma, non-small cell lung, esophageal, and head and neck cancer, among others, are intrinsically resistant to apoptosis induction and poorly responsive to current therapies with proapoptotic agents. In addition, tumors often develop multidrug resistance based on the cellular efflux of chemotherapeutic agents. Thus, novel anticancer agents capable of overcoming these intrinsic or developed tumor resistance mechanisms are urgently needed. We describe a series of 2-aryl-2-(3-indolyl)acetohydroxamic acids that are active against apoptosis- and multidrug-resistant cancer cells as well as glioblastoma neurosphere stemlike cell cultures derived from patients. Thus, the described compounds serve as a novel chemical scaffold for the development of potentially highly effective clinical cancer drugs.

One-pot synthesis of benzoxazoles via the metal-free ortho-C–H functionalization of phenols with nitroalkanes

PPA-activated nitroalkanes are employed in the design of a one-pot cascade transformation involving metal-free and oxidant-free direct ortho-C–H functionalization, followed by Beckman rearrangement and intramolecular cyclocondensation to produce benzoxazoles and benzobisoxazoles directly from easily available phenols.

Arenes and Hetarenes in Reactions with unsaturated Nitro Compounds (Review)

Data on the reactions of unsaturated nitro compounds with aromatic and heteroaromatic compounds over the last 65 years and also their reactions under the conditions of asymmetric catalysis are examined and summarized.

6(7)-Acylperimidines nitration and methods of peri -annelation on this base

A method has been developed for the nitration of 6(7)-acylperimidines using sodium nitrite in formic acid. The reaction gives a mixture of 4(9)-, 9(4)-, and 7(6)-nitro-6(7)-acylperimidines from which the latter can be separated by extraction with chloroform. Reduction of the 6(7)-acyl-7(6)-nitro- perimidines yields 1H-1,5,7-triazacyclopenta[cd]phenalenes. Subsequent Schmidt reaction and reduction give 1,3,6,8-tetraazapyrenes.

An efficient synthesis of (3-indolyl)acetonitriles by reduction of hydroxamic acids

A new, highly efficient method was developed for the synthesis of (3-indolyl)acetonitriles by reduction of readily available (3-indolyl)hydroxamic acids with phosphorus trichloride. The nitriles obtained according to this method are of significant interest for structure-activity studies of potential anticancer agents.

A novel method for the synthesis of 1,8-dihydropyrido[2,3,4-gh]perimidin-7(6H)-ones

Many organic luminphores and dyes are polynuclear aromatic and heteroaromatic compounds, including pyrene and its heterocyclic analogs. Effective medicines, (e.g., the antitumor compound AG 311) and luminescent intercalators have been discovered on the basis of 4,9-diazapyrenes [1-3]. At this time the majority of azapyrenes are unavailable. Primarily this is due to the absence of efficient methods for the peri-annelation of heterocyclic rings. In this study, we propose a method for the peri-annelation of an [ab]pyridine ring to perimidines, which is based on a previously unknown intramolecular variant of our recently discovered acetamidation of aromatic compounds using nitroalkanes in polyphosphoric acid (PPA) [4, 5]. We have shown that the reaction of the perimidines 1a-c with 1.05-fold molar excess of β-nitrostyrene (2) in PPA for 5 h at 65-70oC led to previously unknown 8-phenyl-1,8-dihydropyrido[2,3,4-gh]perimidin7(6H)-ones 6a-c in 76-84% yields. The reaction mechanism probably includes formation from perimidines 1a-c and -nitrostyrene (2) of the nitro compounds 3a-c, which take part in an intramolecular acetamidation of aromatic compounds (as noted above) via formation of oximes 5a-c and a Beckmann rearrangement of the latter. IR spectra were recorded on a Specord 75 IR instrument in KBr pellets. H and C NMR spectra were recorded on a Bruker DRX-500 instrument (500 and 125 MHz, respectively) using DMSO-d6 with TMS as internal standard. Elemental analysis was carried out on a KOVO CHN-1 CHN analyzer. Melting points were determined on a PTP-M apparatus (Khimlaborpribor). Monitoring of the reaction course and the purity of the synthesized compounds was carried out on Silufol UV-254 plates with EtOAc as eluent. Commercial PPA was used with an 80% P2O5 content. 8-Phenyl-1,8-dihydropyrido[2,3,4-gh]perimidin-7(6H)-ones 6a-c (General Method). A mixture of perimidine 1a-c (1.00 mmol) and -nitrostyrene (2) (0.157 g ,1.05 mmol) in 80% PPA (2-3 g) was heated for 5 h at 65-70oCwith vigorous stirring. The reaction mixture was then poured into water (30 ml) and neutralized with ammonia solution. The precipitate formed was filtered off and washed with water (350 ml) and EtOAc (350 ml). The residue was a practically pure substance, which could be recrystallized from EtOAc if needed.