Synthesis and in vitro antiproliferative activity of novel androst-5-ene triazolyl and tetrazolyl derivatives

A straightforward and reliable method for the regioselective synthesis of steroidal 1,4-disubstituted triazoles and 1,5-disubstituted tetrazoles via copper(I)-catalyzed cycloadditions is reported. Heterocycle moieties were efficiently introduced onto the starting azide compound 3β-acetoxy-16β-azidomethylandrost-5-en-17β-ol through use of the "click" chemistry approach. The antiproliferative activities of the newly-synthesized triazoles were determined in vitro on three human gynecological cell lines (HeLa, MCF7 and A2780) using the microculture tetrazolium assay.     

Lanthanide dota-like complexes containing a picolinate pendant: structural entry for the design of Ln(III)-based luminescent probes

In this contribution we present two ligands based on a do3a platform containing a picolinate group attached to the fourth nitrogen atom of the cyclen unit, which are designed for stable lanthanide complexation in aqueous solutions. Potentiometric measurements reveal that the thermodynamic stability of the complexes is very high (log K = 21.2-23.5), being comparable to that of the dota analogues. Luminescence lifetime measurements performed on solutions of the Eu(III) and Tb(III) complexes indicate that the complexes are nine coordinate with no inner-sphere water molecules. A combination of density functional theory (DFT) calculations and NMR measurements shows that for the complexes of the heaviest lanthanides there is a major isomer in solution consisting of the enantiomeric pair Λ(δδδδ) and Δ(λλλλ), which provides square antiprismatic coordination (SAP) around the metal ion. Analysis of the Yb(III)-induced paramagnetic shifts unambiguously confirms that these complexes have SAP coordination in aqueous solution. For the light lanthanide ions however both the SAP and twisted-square antiprismatic (TSAP) isomers are present in solution. Inversion of the cyclen ring appears to be the rate-determining step for the Λ(δδδδ) ? Δ(λλλλ) enantiomerization process observed in the Lu(III) complexes. The energy barriers obtained from NMR measurements for this dynamic process are in excellent agreement with those predicted by DFT calculations. The energy barriers calculated for the arm-rotation process are considerably lower than those obtained for the ring-inversion path. Kinetic studies show that replacement of an acetate arm of dota by a picolinate pendant results in a 3-fold increase in the formation rate of the corresponding Eu(III) complexes and a significant increase of the rates of acid-catalyzed dissociation of the complexes. However, these rates are 1-2 orders of magnitude lower than those of do3a analogues, which shows that the complexes reported herein are remarkably inert with respect to metal ion dissociation.     

An inverse theorem for the restricted set addition in Abelian groups

Let A be a set of k5 elements of an Abelian group G in which the order of the smallest nonzero subgroup is larger than 2k−3. Then the number of different elements of G that can be written in the form a+a^′, where a,a^′A, a≠a^′, is at least 2k−3, as it has been shown in [Gy. Károlyi, The Erdős–Heilbronn problem in Abelian groups, Israel J. Math. 139 (2004) 349–359]. Here we prove that the bound is attained if and only if the elements of A form an arithmetic progression in G, thus completing the solution of a problem of Erdős and Heilbronn. The proof is based on the so-called ‘Combinatorial Nullstellensatz.’     

New practical synthesis of 5‐formylindole

5‐Formylindole ( 2 ) was synthesized in good overall yield starting from 3‐methyl‐4‐nitrobenzaldehyde ( 4 ) by utilization of the Batcho‐Leimgruber indole synthesis.     

Synthesis of isoquinobenzodiazepinediones

1-(2′-Chloroacetylamino)-4,4-dimethyl-1,4-dihydro-3(2H)-isoquinolinone ( 3 ) was cyclised by treatment with sodium hydride in dimethyl sulphoxide containing 0.1 % of water to give 10,10-dimethyl-6,7,9,10-tetrahydro-5H,14bH-isoquino[2,1-d][1,4]benzodiazepine-6,9-dione ( 4 ) in a yield of 80%. In anhydrous dimethyl sulphoxide the main product of the reaction was 5-N-(4,4-dimethyl-1-phenyl-1,4-dihydro-3(2H)-isoquinolinon-1′-yl)isoquino[2,1-d][1,4]benzodiazepine-6,9-dione ( 5 ), which was also prepared by the reaction of 3 with 4 .     

Konvexes Polyeder als geometrischer Ort

Ohne Zusammenfassung Aus dem Nachlaß des Verfassers bearbeitet durch L. Fejes Tóth     

The ring closure and rearrangement of N-2-aminobenzoyl -N-methylhydrazones of β-dicarbonyl compounds

A novel rearrangement was observed during the cyclization of N-(2-aminobenzoyl)-N-methylhydrazones of β-dicarbonyl compounds, leading to pyrazole derivatives 2,4, and 5 depending on substituents and the reaction media.