Synthesis and antibacterial study of unsaturated Mannich ketones.

Several Mannich ketones of 2-arylmethylenecycloalkanones were synthesised using the classical acid-catalysed Mannich reaction. Antibacterial activity of these new water-soluble compounds was reported against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Staphylococcus saprophyticus, Micrococcus luteus and Bacillus subtilis standard strains. Human cell line cytotoxicity of our new compounds was evaluated against HeLa cell lines. Some compounds showed low cytotoxicity (41.52 nM mL(-1) for 14 and 46.60 nM mL(-1) for 18) and proved to be efficient antibacterial agents against the Gram-positive strains. Minimum inhibitory concentrations varied from 1.56 to 100 microg mL(-1). The mechanism of action was examined, too.

Efficient synthesis of fused isothiazolo C-nucleosides. III. Synthesis of substituted isothiazol.

The Divakar-Reese procedure has been successfully applied for transforming 7-oxo-isothiazolo[4,5-d]pyrimidine C-nucleosides (4a,b, 5a,b, 6a) via 1,2,4-triazol-1-yl intermediates (7a,b, 8a,b) into various 7-substituted C-nucleosides 15a,b, 16a,b, 17a, 18a, 19a,b, 20a,b; their subsequent deprotection provides novel types of unusual C-glycosides 22b, 23a, 24a,b, 25b, 26b. C-Nucleosides, possessing on its heterocyclic base other than naturally occuring oxo- or amino substituents, are important model compounds for biological or medicinal studies (2,3). We want to report on the synthesis of novel 7-substituted isothiazolo = [4,5-d]pyrimidine C-nucleosides. As we could show in previous papers (1,4), there exists a simple approach to the protected C-glycosides 4-6.

An efficient synthesis of thioisomunchnones derived from uracils and uridine: novel type of mesoionic nucleosides

[reaction: see text] Synthetic approaches to a variety of thioisomunchnones derived from uracils and uridine are described, as well as their properties and cycloaddition tendencies. The anhydro-3-hydrocy-2-phenyl-6-(2',3',5'-tri-O-benzoyl-beta-D-ribofuranosyl)thiazolo[3,2-c]pyrimidine-5(6H)-on-4-ium hydroxide represents a novel class of mesoionic nucleosides.

Study on steroidal oximinoethers: synthesis and stereostructure by NMR spectroscopy.

The condensation of O-substituted hydroxylamines with conjugated 3-oxo-4-en steroids results in a mixture of syn-anti configurations. Syn-anti ratios are influenced by sterical hindrance between the oximino substituents (e.g. O-benzyl) and the steroidal skeleton. Stereostructures and isomeric ratios were proved by detailed 1H and 13C NMR studies and also by using 2D-COSY, 2D-HSC, DEPT, 2D-COLOC and DNOE measurements.

2-Substituted indazoles. Synthesis and antimicrobial activity.

2-Isothiocarbamoyl substituted fused pyrazolines and their S-alkyl derivatives were prepared as potentially antimicrobial agents. Conventional methods were used to synthesize the novel derivatives starting from cyclic unsaturated ketones and thiosemicarbazide under acidic catalyst. These cyclizations yielded only one diastereoisomer of 3-H, 3a-H cis. The alkylations were performed applying alkyl halides. The structures of the new compounds, including configurations and conformations, were elucidated by NMR spectroscopy, also making use of 2D-HSC, DEPT and DNOE measurements. The S-alkyl derivatives were evaluated for activity against Gram-negative and Gram-positive bacteria and their in vitro toxicity was determined on HeLa cells. The structure-activity relationship was also studied.

[Preparation and steric structure elucidation of saturated or partially saturated isoindolo[2,1-a][3,1]benzoxazinones, -[1,2-b][2,4]benzoxazepinones, cyclopentane- and -cyclohexane[b]pyrrolo[2,1-a][3,1]-benzoxazines]. / Telített és részlegesen telített izoindolo[2,1-a] [3,1]benzoxazinok, -[1,2-b][2,4]benzoxazepinonok, ciklopentán- és -hexán[b]pirrolo[2,1-a][3,1]benzoxazin izomerek szintézise.

The reactions of 2-carboxybenzaldehyde (1) with 1,3- or 1,4-aminoalcohols (2a-i, 3a,b) were used to prepare partially or fully saturated tetra- and pentacyclic compounds containing a condensed 1,3-oxazino- or oxazepinoisoindolone moiety and one terminal saturated carbocycle. Isoindolo[2,1-a][3,1]benzoxazinones (4a-d, 6, 7), stereoisomeric isoindolo[1,2-b][2,4]benzoxazepinones (5a-c) hexahydrocyclopentane[b]pyrrolo[1,2-a][3,1]-benzoxazinone (10a,b), octahydroindolo[1,2-b]- and decahydroindolo[1,2-a]benzoxazinone (11a,b and 12a,b) and related pentacyclic derivatives (4e-g) were prepared. The diastereomers 5a-c differ in the ring annelation or in the position of the NCHO hydrogens and annelational hydrogens. The stereostructures of these compounds were elucidated by means of 1H and 13C NMR spectroscopy, including DNOE, DEPT, 2D-HSC measurements and X-ray analysis.

[Saturated heterocyclic compounds. 216 (1). Synthesis, structure and ring opening of trans-perhydro-1,4-benzoxazepin-3-one derivatives]. / Telített heterociklusok, 216 [1]. Transz-Perhidro-1, 4-benzoxazepin-3-on származékok szintézise és gyürüfelnyílása.

trans-Perhydro-1,4-benzoxazepin-3-ones 2a-e were synthesized and transformed to condensed-skeleton perhydro-trans-1,4-benzoxazepines 3a,b, the thiones 4a,b, the urea derivatives 5a,b, and N-acylated compounds 6a-e. Compounds 6b,d were ring-opened by hydrochloride acid in ethanol to yield trans-2 (1-carbethoxyethoxy)-1-(acylaminomethyl)-cyclohexane derivatives 7b,d. The 1H- and 13C-nmr investigation and X-ray analysis of 5b and 6c,d proved that the expected N-acylated derivatives were formed and that both rings of the annolated compounds have a chair conformation.

[Synthesis of quinazolino-1,3-benzothiazine derivatives]. / Kinazolino-1,3-benztiazinszármazékok szintézise.

The ring-closure reactions of N-(3,4-dimethoxyphenylthio-methyl)-2-nitrobenzamide derivatives 5a,b with phosphoryl chloride gave 4-(2'-nitrophenyl)-2H-1,3-benzothiazine derivatives 7a,b, which on reduction yielded 4-(2'-aminophenyl)-3,4-dihydro-2H-1,3-benzothiazines 8a,b. Reaction of these compounds with phosgene led to the derivatives 9a,b of a new heterocyclic ring system, 6H,8H-quinazolino[3,4-c] [1,3]benzothiazine. The structures of the title compounds were proved by their ir and nmr (1H, 13C) spectra.

[Synthesis of tert-butylcyclopentane-fused 1,3-oxazines and 1,3-thiazines]. / terc-Butil-ciklopentánnal kondenzált 1,3-oxazinok és 1,3-tiazinok szintézise.

Chlorosulphonyl isocyanate (CSI) addition to 4-tert-butylcyclopentene furnished the azetidinone (3) in a stereospecific reaction. Azetidinone 3 was transformed by ring opening esterification and lithium aluminium hydride (LAH) reduction to the 2-hydroxy-methyl-4-tert-butyl-1-cyclopentylamine (6). The N-methyl-aminoalcohol (8) was prepared from amino esters (5) with ethyl chloroformate and subsequent LAH reduction. By different ring-closure methods, a number of tert-butyl-cyclopentante-fused 1,3-oxazines and 1,3-thiazines were synthesized. A comparative study of the prepared compounds was performed by IR, 1H- and 13C-NMR, DEPT and DNOE measurements.

[Preparation and steric structure of condensed-skeleton saturated diphenyl-substituted isoindolones]. / Kondenzáltvázas telített difenilszubsztituált izoindolonok elöállítása és szerkezete.

The Friedel-Crafts reaction of benzene with cis-4-cyclohexene-1,2-dicarboxylic anhydride (1) yields trans-5-phenyl-cis-2-benzoylcyclohexanecarboxylic acid (2), which gave cyclohexane-condensed pyridazinone (3) with hydrazine, and cis-4,5-tetramethylene-1,2-oxazin-8-one (4) with hydroxylamine. From 2 with ethylenediamine, the saturated imidazol[2,3-a]iso-indolone (5) was prepared, while the reaction of 2 with 1,3-diaminopropane furnished a mixture of two isomeric pyrimido[2,3-a]isoindolones (6a,b) in the relative positions of the benzene ring and cyclohexane annelation hydrogens. From the reaction of 2 with 3-aminopropanol, the oxazino[2,3-a]isoindolone (7) was obtained. The reaction of 2 with cis-2-hydroxymethylcyclohexylamine gave the tetracyclic (8), while 2 and diendo-3-hydroxymethylbicyclo[2.2.1]hept-5-enyl-2-amine yielded the isomers (9a,b), which differ in the mutual positions of the phenyl group on the quaternary carbon and cyclohexane annelation hydrogens. 1H and 13C-nmr spectra and DNOE and 2D-HSC measurements proved that the 5-phenyl group is cis-equatorial to the two annelated hydrogens of the cyclohexane ring.

[tert-Butylation of the tryptophan indole ring during the removal of the tert-butyloxycarbonyl group (author's transl)]. / tert-Butylierung des Tryptophan-Indolringes während der Abspaltung der tert-Butyloxycarbonyl-Gruppe bei Peptidsynthesen.

The tert-butylation of the tryptophan indole ring during the removal of tert-butyloxycarbonyl groups under different conditions was studied. The incorporation of tert-butyl groups was measured by a 1H-NMR technique. It was established, that the rate and specificity of the tert-butylation is highly dependent on the character of the cleaving reagents used and on the environment of the tryptophan residue in the peptide chain.

1,6-anhydro-1(6)-thio-L-iditol and -D-mannitol, and some derivatives thereof.

Starting from 1,2:5,6-dianhydro-3,4-O-isopropylidene-L-iditol (1) and -D-mannitol (6), respectively, the corresponding 1,6-anhydro-1,(6)-thio derivatives (2a and 7a) were synthesized. The discrepancy in the yields obtained, as well as the different behavior of their methylated derivatives (2e and 7c) towards acid hydrolysis, could be explained by steric factors. The di-O-mesyl derivatives 3d and 12c were unstable compounds, and showed no ulcerostatic activity, unlike the D-glucitol analog.

Derivatives of 2,3-anhydro-DL-threitol, 2,3-anhydroerythritol, 2,3:4,5-dianhydrogalactitol, and 2,3:4,5-dianhydroallitol.

alpha, omega-Disubstituted derivatives of 2,3-anhydro-DL-threitol (2), 2,3-anhydroerythritol (4), 2,3:4,5-dianhydrogalactitol (8), and 2,3:4,5-dianhydroallitol (12) have been synthesised by epoxidation of the appropriate alkeness and dienes. Benzyloxy carbonyl groups were used for protecting the primary hydroxyl groups during epoxidation.