Štefan Marchalín

Synthesis of benzo(or furo)[5,6]azepino[2,1-a]isoindolone derivatives: π-cyclisations of N-acyliminium ions

Benzo(or furo)[5,6]azepino[2,1-a]isoindolone and derivatives were obtained easily in one-pot via N-acyliminium ions by treatment of 2-(2-methoxycarbonylbenzyl(or fur-3-yl))phthalimide with alkylmagnesium iodide followed by an acidic hydrolysis.

The Improved Synthesis of Enantiopure (S)-N-Arylmethyl-5-Oxoprolines

Abstract A mild procedure for the preparation of enantiopure N-alkylated (S)-(+)-5-oxoprolines 3a-r is described. The method starting from (S)-glutamic acid appears generally applicable to substrates with a wide range of substituents.

Newly synthesized indolizine derivatives – antimicrobial and antimutagenic properties

A series of indolizine derivatives have been synthesized and subjected to antibacterial screening studies. Antibacterial activity of 21 derivatives was investigated against Staphylococcus aureus, Mycobacterium smegmatis, Salmonella typhimurium and Escherichia coli; also, the sensitivity of model yeast Candida parapsilosis and some model filamentous fungi Aspergillus fumigatus, Alternaria alternata, Botrytis cinerea and Microsporum gypseum was tested. Newly synthesized indolizine derivatives have shown selective toxicity to Gram-positive bacteria S. aureus and were also considered to be able to inhibit the acidoresistant rod M. smegmatis. Derivative XXI has shown the highest inhibition effect with the bacteriostatic effect on the cells at the concentration of 25 µg mL−1. The best antifungal activity has been detected in the presence of derivative XIII. Derivative XIII did also affect the morphology of hyphal tips of B. cinerea, which led to enhanced ramification of hyphae. Finally, the antimutagenic activity of derivatives was investigated. Significant antimutagenic activity was registered in case of derivative VIII. The number of induced revertants by mutagen [2-(5-nitrofuryl)acrylic acid] was decreased almost to the level of spontaneous revertants in the lowest applied concentration (50 µg per plate).

2,4,4a,5,6,7,9,9a-Octahydrofuro[2,3-f]indolizin-7-one

In the title compound, C10H13NO2, the conformation of the oxopyrrolidine ring is close to that of an envelope. The central six-membered ring has a chair conformation. The nearly planar furan ring attached to the indolizine ring system is slightly buckled, with a mean deviation of 0.037 A.

(3aS,8aS,9R,9aS)-9-Hydroxy-2,3,3a,7,8,8a,9,9a-octahydrofuro[3,2-f]indolizin-6(4H)-one

In the title compound, C10H15NO3, the central six-membered ring has a chair conformation. The conformations of the fused furan and oxopyrrolidine rings are close to envelopes. Molecules form chains parallel to the b axis, via O-H...O intermolecular hydrogen bonds.

2-Acetyl-3-(5-cyano-2-furyl)propenenitrile

The crystal structure of the title compound, C 10 H 6 N 2 O 2 , : consists of relatively isolated molecules, the shortest intermolecular contacts [C-H...O 2.51 (2); C-H...N 2.50(1) and 2.60(2)A] indicate the presence of weak hydrogen bonding. As indicated by the planarity of the molecule and the pattern of bond lengths, the π-electron delocalization extends over the whole molecule.

Asymmetric synthesis and study of biological activity of (epi-)benzoanalogues of bioactive phenanthroquinolizidine alkaloids

The increasing microbial resistance to primary active structures remains alarming and the effort to look for new antibacterial active structures is still of scientific interest. One of the attractive ways to find new active structures is derivatization of well-known natural compounds. Alkaloids are a structurally diverse group of natural products with a wide range of biological effects. Historically, an attempt to increase the antimicrobial activity of alkaloids through chemical modifications has been successful. In this work, 12 new quinolizidine derivatives were synthesized and tested for their antimicrobial activity. The asymmetric synthesis of the benzoanalogue of the phenanthroquinolizidine bioactive alkaloid (−)-cryptopleurine and the epi-benzoanalogues of (−)-(15R)-hydroxycryptopleurine were achieved in six or seven steps starting from available enantiopure (S)-2-aminoadipic acid used as source of chirality as well as nitrogen. The highest antimicrobial activity was observed in the presence of the final saturated structure, the benzoanalogue of naturally occurring plant alkaloid cryptopleurine. It features selective toxicity, and significantly inhibits the growth of G+ bacteria, especially Staphylococcus sp. Tested derivatives have shown only a weak antifungal activity, but partial inhibition has been observed in the case of model yeasts.Graphical abstract

Crystallographic characterization of a novel spiro-[chroman-chromene]-carboxylate

Abstract We report here the crystal and electronic structure of a new spiro-derivative, namely methyl (2R,4S)- 4-(benzothiazol-2-ylamino)-8,8´-dimethoxyspiro[chroman-2,2´-chromene]-3´-carboxylate (I), C28H24N2O6S, which crystallizes as racemate in the space group C2/c. In this compound, the chromanone moiety consists of a benzene ring fused with a six-membered heterocyclic ring which adopts a distorted half-chair conformation. The molecules are linked by a combination of N-H∙∙∙N hydrogen bonds and weak C-H∙∙∙O, C-H∙∙∙S, C-H∙∙∙ π, inter- and intra-molecular interactions resulting in a two-dimensional network in the crystal structure.

(4R,1'S)-Diethyl 6-methyl-2-[(1'-phenylethylimino)methyl]-4-(2-thienyl)-1,4-dihydropyridine-3,5-dicarboxylate

The absolute configuration of the title compound, C25H28N2O4S, has been determined. The 1,4-dihydropyridine (1,4-DHP) ring has the usual shallow boat conformation. The thiophene ring is approximately perpendicular to the plane through the four atoms of the base of the boat. The two ester groups are twisted in the same direction and have a cis,cis geometry with respect to the adjacent ring double bonds.

(3aS,5aR,10aS,11aR)-2,2-Dimethyl-3a,9,10,10a,11,11a-hexahydro-5aH-1,3-dioxolo[4,5:3',4']furo[2',3'-f]indolizin-8(4H)-one

In the crystal structure of the title compound, C13H19NO4, there are two molecules in the asymmetric unit. The crystal which was used for collecting intensity data was twinned. The furoindolizine ring system adopts a fused envelope-chair-envelope conformation. The packing is stabilized by intermolecular C-H...O hydrogen bonds.