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Grinev V. S., Linkova E. I., Yegorova A. Y. Синтез и конформационные особенности пергидропирролодиазациклоалканонов. Izvestiya of Saratov University. New series. Series: Chemistry. Biology. Ecology, 2020, vol. 20, iss. 2, pp. 122-130. DOI: https://doi.org/10.18500/1816-9775-2020-20-2-122-130


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547.415.1’435.1’484.2’745.04:543.422.25
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Russian

Синтез и конформационные особенности пергидропирролодиазациклоалканонов

Abstract

The reactions of 4-phenyl and 4-(p-tolyl)-4-oxobutanoic acids with 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane by heating in an aprotic non-polar solvent initially proceed through a nucleophilic attack of the amino group on the carbon atom of the oxoacid carbonyl group to form the corresponding amide. Subsequent intramolecular cyclodehydration leads to pyrrolidone, which, in turn, undergoes heterocyclization with the formation of the corresponding bicyclic products 8a-phenyl- and 8-(p-tolyl)-hexahydropyrrolo [1,2-a]pyrimidin-6(2H)-one (1a,b), 9a-phenyl- and 9a-(p-tolyl)-octahydro-7H-pyrrolo[1,2-a][1,3]diazepin-7-one (2a,b), 10a-phenyland 10a-(p-tolyl)-octahydropyrrolo[1,2-a][1,3]diazocin-8(2H)-one (3a,b). The use of longer chain terminal binucleophiles, such as 1,5-diaminopentane under conditions of synthesis in benzene or toluene did not lead to double heterocyclization with the formation of fused bicyclic structures and the reaction stopped at the stage of amide formation. The corresponding bicyclic 10a-phenyl- and 10a-(p-tolyl)-octahydropyrrolo[1,2-a][1,3]diazocin-8(2H)-ones (3a,b) were only obtained using a higher boiling o-xylene, which is most likely due to the conformational difficulties in steric convergence of reacting groups. The structures of the obtained compounds were determined using the dataset of the elemental analysis, IR, 1H NMR spectroscopy data. The study of the conformational capabilities of the synthesized compounds, which are important from the point of view of structure-activity relationships (SAR), showed that the presence of several methylene units in molecules of compounds 1–3 of several methylene units, as well as a side aromatic substituent capable of rotating around a simple C–C bond, determines their wide conformational properties, and as a result, a potentially high affinity for a wide range of receptors.

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