Band 21, Heft 1

A novel compound 6-amino-2-thiaspiro[3,3]heptane hydrochloride was synthesized in nine steps using 2,2-bis(bromomethyl)-1,3-propanediol as starting material, with an overall yield of 31%.

In the improved synthesis of 6-[(ethylthio)methyl]-1 H -indazole ( 5 ), the mesylate intermediate is replaced by the bromide derivative, which increases the overall yield (six steps) by a factor of 3.

A simple and practical approach to oxindole derivatives via organoselenium-induced radical cyclizations of N -arylacrylamides has been developed. This method provides a convenient access to a variety of selenium-containing oxindoles in good to excellent yields under relatively mild reaction conditions. As one of its notable features, the radical process allows for the direct formation of a Se-C bond and the construction of a oxindole ring in one reaction.

A series of N -(arylpiperazinyl)acetamide derivatives of 1,3- and 3,7-dimethyl-1 H -purine-2,6(3 H ,7 H )-dione was synthesized and biologically evaluated in in vitro competition binding experiments for serotonin 5-HT 6 , 5-HT 7 , and dopamine D 2 receptors. The structure-affinity relationships for this group of compounds allowed for determination of structural features responsible for receptor affinity. Among the investigated derivatives, compounds 5 and 12 with (2,3-dichlorophenyl)piperazine moiety were classified as potent dual 5-HT 6 /D 2 receptors ligands, whereas compound 4 , with 4-(benzo[ d ]isothiazol-3-yl)piperazine moiety, and compounds 8 and 15 , with (2,3-dichlorophenyl)piperazine moiety, were classified as potent D 2 receptor ligands.

A series of 38 new derivatives of cyclic imides containing silicon in the structure was synthesized and characterized by 1 H NMR, ESI-MS, and elemental analysis. Selected compounds ( 1l,m , 1g , 1o,p , 2l,m , and 2o,p ) were tested for their cytotoxic properties in human chronic myelogenous leukemia (K562), human cervical cancer (HeLa), and normal endothelial cells (HUVEC). Seven compounds showed significant cytotoxicity. In addition, two compounds ( 1l and 2l ) were tested toward affinity for 5-HT 1A , 5-HT 6 , and 5-HT 7 serotonin receptors, and all aryl/heteroarylopiperazino derivatives were tested for antimicrobial activity. The compounds tested toward affinity for selected serotonin receptors showed high and moderate affinity for 5-HT 1A and 5-HT 7 , while the antimicrobial activity of tested compounds was not significant.

Quinoxaline derivatives 4–11 were synthesized and evaluated for their in vitro growth inhibitory activities against liver carcinoma cell line (HEPG 2 ) using the sulforhodiamine B assay. The synthesis was achieved by reaction of 2,3-dichloroquinoxalines 2a,b with 4-aminoacetophenone to give the corresponding compounds 3a,b . Claisen-Schmidt condensation reaction of 3a,b with furfuraldehyde gave enones 4a,b , which were transformed into pyridines 6a,b , 8a,b , isoxazolines 9a,b , pyrazolines 10a–d , and pyrimidines 11a,b via several synthetic routes. Virtual screening was carried out by molecular modeling evaluation of the designed compounds. Biological evaluation of the prepared compounds showed that most of the synthesized compounds exhibit more than 50% growth inhibitory.

The oxidation of Baylis-Hillman adducts, obtained by the reaction of 5-benzyloxy-2-formyl-4-pyrone, with o -iodoxybenzoic acid generates β-ketomethylene intermediates that in situ undergo conjugative attack of NH-containing heterocycles such as imidazole and pyrazoles.

The stereoselective synthesis of a 1,2,3-triazolo-δ-lactone (+)- 6 derived from a homoallyl alcohol ( S )-(-)- 1 backbone was accomplished. 2-Thienyl-substituted allyl alcohol ra c- 1 was efficiently resolved through enzymatic method with high ee (95%) and known stereochemistry. An enantiomerically enriched azidoalcohol (+)- 4 derived from a homoallyl alcohol was subjected to the Huisgen 1,3-dipolar cycloaddition reaction with diethyl acetylenedicarboxylate, followed by intramolecular cyclization of the corresponding cycloadduct (+)- 5 , to yield the 1,2,3-triazolo-δ-lactone derivative.

The reaction of dimethyldioxirane ( 1 ) with excess 1,3-cyclohexadiene ( 2a ) and 1,3-cyclooctadiene ( 2b ) in dried acetone yielded the corresponding monoepoxides in excellent yield. Second-order rate constants for monoepoxidation were determined using UV methodology. The k 2 value for the monoepoxidation of 1,3-cyclohexadiene was found to be 1.14±0.06 m -1 s -1 , whereas that for the monoepoxidation of 1,3-cycloctadiene was 0.31±0.03 m -1 s -1 . Basic density functional calculations at the B3LYP/6-31G level were employed to model the monoepoxidations. As expected, the calculations were consistent with a concerted, electrophilic process with a spiro-transition state. As found for the epoxidation of simple alkenes, the calculated transition-state geometry showed a slight asynchronous tilt of the dioxirane plane relative to that of the remaining alkene portion of the diene and a slight tilt back from the face of the diene. Relative reactivities (relative k 2 values) were determined using the difference in the calculated electronic activation energies and were consistent with the experimental relative k 2 values without the need to correct for the medium (solvent). Reactivity differences for epoxidation can be quickly predicted by this approach as long as there are reasonable structural similarities between the substrates.

Novel rel -(5 R ,6 S ,7 S )-2-oxo-5,7-diaryl-3,5,6,7-tetrahydro- 2H -thiopyrano[2,3- d ]thiazol-6-yl-oxo-acetic acids were synthesized in 52–70% yields via regioselective and diastereoselective hetero -Diels-Alder reaction of 5-arylidene-4-thioxo-2-thiazolidinones with a series of arylidene pyruvic acids. The synthesized compounds were evaluated for anticancer activity in NCI60 cancer cell lines and for antiexudative activity on the carrageenan edema model in rats. Biological screening data led to identification of 3e as having moderate antitumor activity on the colon cancer HT-29 cell line and of 3b as having promising antiexudative effect.