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Abstract: Using 3β-hydroxychol-5-en-24-oic acid (4) as starting material, the diastereoisomeric allylic alcohols (24E)-26-hydroxydesmosterol (2) and (24Z)-26-hydroxydesmosterol (3) have been synthesised in six steps with 67% and 12% overall yield, respectively. Both of these isomers are found in newborn mouse brain where sterol synthesis is high. Unlike desmosterol (1), neither of these isomers is a ligand to the liver x receptors and thus represents a novel biological deactivation mechanism avoiding cholesterol synthesis. [Copyright &y& Elsevier]

Graphical abstract Highlights • Twelve pyridoxine-based bioisosteric analogs of dehydrozingerone are synthesized. • At least 8 compounds possess high in vitro antitumor activity and selectivity. • The active compounds inhibit migration of tumor cells and arrest their cell cycle. • They also increase the level of reactive oxygen species and initiate apoptosis. • The leading compound also affects the functional activity of mitochondria. Abstract Two series of novel pyridoxine-based azaheterocyclic analogs of feruloyl methane (Dehydrozingerone, DZG) were synthesized, and their biological activity against a panel of tumor and normal cell lines was evaluated in vitro. The most active compounds possessed expressed cytotoxic activity, which was comparable to cytotoxic activity of doxorubicin and significantly higher than that of DZG, and a remarkable selectivity for the studied cancer cell lines as compared to the normal cells. The leading compound and DZG initiated arrest of the cell cycle in the G2/M phase, preventing normal division and further transition of daughter cells to the G0/G1 phase. Similar to DZG, but with higher efficiency, the leading compound was able to inhibit migration activity and, therefore, invasiveness of tumor cells. It also increased concentration of reactive oxygen species in tumor cells, induced depolarization of mitochondrial membranes and initiated apoptosis accompanied by disruption of integrity of cytoplasmic cell membranes. By contrast to DZG, the leading compound did not possess antioxidant properties. The obtained data make the described chemotype a promising starting point for the development of new anticancer agents. [ABSTRACT FROM AUTHOR]

The PBu 3 -catalyzed conjugate addition of diphenylphosphine oxide to unsubstituted and substituted electron-deficient alkenes is reported. β-Substituted α,β-unsaturated esters, trans -methyl crotonate and trans -methyl cinnamate, known for their reluctance to participate in phosphine-catalyzed transformations, also react well under the developed conditions. Mild reaction conditions, simple work-up and the ease of catalyst recovery make the proposed methodology useful for the preparation of functionalized tertiary phosphine oxides. The utility of this method was demonstrated by the gram-scale reactions of diphenylphosphine oxide with electron-deficient alkenes. [ABSTRACT FROM AUTHOR]

Wittig reactions of a bis-triphenylphosphonium pyridoxine derivative with five aromatic and aliphatic aldehydes led to a series of mono- and bis-alkenyl substituted products. The reactions also demonstrated unusual reactivity patterns leading to unexpected products, including a Z -shaped hyperconjugated structure with trans -configuration for all three alkene fragments, and a tricyclic 9,10-dihydro-1 H -[1,3]dioxino[4,5- c ]quinoline formed as a result of non-symmetric Wittig olefination followed by a rare type of intramolecular cyclization. The obtained products represent prospective biologically active agents, while one compound is a potential microenvironment- and interaction-sensitive molecular probe. [ABSTRACT FROM AUTHOR]

The interaction of uranyl(VI) nitrate with a series of bis(2-hydroxyaryl)imine (H 2 L 1 –H 2 L 5 ) and bis(2-hydroxyaryl)amine (H 2 L 8 , H 2 L 9 ) derivatives incorporating 1,3-dimethylenebenzene or 1,3-dimethylenecyclohexane bridges between nitrogen sites is reported. Crystalline complexes of type [UO 2 (H 2 L)(NO 3 ) 2 ] (where H 2 L is H 2 L 1 –H 2 L 4 ) were isolated from methanol. X-ray structures of the complexes of H 2 L 1 , H 2 L 2 and H 2 L 4 show that each of these neutral ligands bind to their respective UO 2 2 + centres in a bidentate fashion in which coordination only occurs via each ligand’s hydroxy functions. Two bidentate nitrate anions complete the metal’s coordination sphere in each complex to yield hexagonal bipyramidal coordination geometries. A density functional theory (DFT) investigation of [UO 2 (H 2 L 1 )(NO 3 ) 2 ] in a simulated methanol environment is in accord with this complex maintaining its solid state conformation in solution. Solvent extraction experiments (water/chloroform) employing H 2 L 1 –H 2 L 7 in the organic phase and uranyl(VI) nitrate in the aqueous phase showed that both amine derivatives, H 2 L 8 and H 2 L 9 , yielded enhanced extraction of UO 2 2 + over the corresponding imine derivatives, H 2 L 1 and H 2 L 2 . These results were further compared with those obtained for the corresponding Schiff bases incorporating 1,2-phenylene and 1,2-cyclohexane bridged ligands, H 2 L 6 and H 2 L 7 ; these more rigid systems also yielded enhanced extraction of UO 2 2 + relative to the more flexible Schiff bases H 2 L 1 –H 2 L 5 . A very significant synergistic enhancement of the extraction of UO 2 2 + by H 2 L 1 –H 2 L 4 and H 2 L 7 was observed in the presence of a 10-fold excess of n -octanoic acid; the influence of pH on extraction efficiency was also investigated. A parallel set of experiments employing H 2 L 1 –H 2 L 9 as extractants for europium(III) nitrate indicated a clear uptake preference for UO 2 2 + over Eu 3+ in all cases; separation of the uranyl ion from the rare earths is an important objective in mineral processing. [ABSTRACT FROM AUTHOR]

An efficient PBu 3 -catalyzed α-addition of the P(O)–H bond to ethyl phenylpropiolate has been developed. This strategy offers a facile method for the preparation of synthetically useful alkenyl phosphonates and phosphinates proceeding under neutral reaction conditions with high atom economy. [ABSTRACT FROM AUTHOR]

The seven-membered cyclic bisphosphines 3 – 5 were synthesized by a Mannich-like condensation reaction of 1,2-bis(phenylphosphino)ethane, formaldehyde and primary amines ( tert -butylamine, 1,1-(diphenyl)methylamine, (2 R )-tetrahydro-2-furanylmethylamine) as a mixture of R P R P / S P S P ( rac , 3a – 5a ) and R P S P ( meso , 3b – 5b ) stereoisomers. The structures of the rac stereoisomers 3a – 5a were investigated by X-ray crystal structure analyses. The RR / SS to RS isomerization of 3 – 5 and oxidation processes of 4 in solution were studied. Platinum(II) P,P-chelate complexes are formed exclusively from rac / meso mixtures of 3 – 5 . [ABSTRACT FROM AUTHOR]

[Display omitted] Quarternization of 3-(diphenylphosphino)propanoic acid with ω-haloalkanoic acids affords novel phosphonium salts containing two carboxy groups. The phosphonium salts were treated with 1 M alkali solution to obtain corresponding carboxylate phosphabetaines. The structure of the compounds was established by IR and NMR spectroscopy, elemental analysis and X-ray single crystal diffraction. [ABSTRACT FROM AUTHOR]

Abstract: Interaction of copper(II) salts with 2,2′-dipyridylamine (1), N-cyclohexylmethyl-2,2′-dipyridylamine (2), di-2-pyridylaminomethylbenzene (3), 1,2-bis(di-2-pyridylaminomethyl)-benzene (4), 1,3-bis(di-2-pyridylaminomethyl)benzene (5), 1,4-bis(di-2-pyridylaminomethyl)benzene (6), 1,3,5-tris(di-2-pyridylaminomethyl)benzene (7) and 1,2,4,5-tetrakis(di-2-pyridylaminomethyl)benzene (8) has yielded the following complexes: [Cu(2)(μ-Cl)Cl]2, [Cu(3)(μ-Cl)Cl]2 ·H2O, [Cu2(4)(NO3)4], [Cu2(5)(NO3)4]·2CH3OH, [Cu2(6)(CH3OH)2(NO3)4], [Cu4(8)](NO3)4]·4H2O while complexation of palladium(II) with 1, 4, 5 and 6 gave [Pd(1)2](PF6)2 ·2CH3OH, [Pd2(4)Cl4], [Pd2(4)(OAc)4], [Pd2(5)Cl4], [Pd2(6)Cl4] and [Pd2(6)(OAc)4]·CH2Cl2, respectively. X-ray structures of [Cu(2)(μ-Cl)Cl]2, [Cu(3)(μ-Cl)Cl]2 ·2C2H5OH, [Cu2(6)(CH3OH)2(NO3)4], [Pd(1)2](PF6)2 ·2CH3OH, [Pd2(4)(OAc)4]·4H2O and [Pd2(6)(OAc)4]·2CH2Cl2 are reported. In part, the inherent flexibility of the respective ligands has resulted in the adoption of a diverse range of coordination geometries and lattice arrangements, with the structures of [Pd2(4)(OAc)4] · 4H2O and [Pd2(6)(OAc)4]·2CH2Cl2, incorporating the isomeric ligands 4 and 6, showing some common features. Liquid–liquid (H2O/CHCl3) extraction experiments involving copper(II) and 1–3, 5, 7and 8 show that the degree of extraction depends markedly on the number of dpa-subunits (and concomitant lipophilicity) of the ligand employed with the tetrakis-dpa derivative 8 acting as the most efficient extractant of the six ligand systems investigated. [Copyright &y& Elsevier]

Abstract: Alkylation of γ- and δ-sultams with (iodomethyl)trimethylsilane followed by treatment of the resultant silanes with tetrabutylammonium fluoride gave rise to sulfur-free unsaturated amines. In particular, N-THP substituted sultams were found to be useful substrates for the alkylation event. A corresponding one-pot transformation involving sultam α-alkylation with (iodomethyl)magnesium chloride is also reported. [Copyright &y& Elsevier]

• Novel pyridoxine-based bioisosteric analogs of estradiol are synthesized. • Several compounds possess high in vitro antitumor activity and selectivity. • The lead compound induces apoptosis in MCF-7 but not in MDA-MB-231 cells. A new efficient approach to the synthesis of 6-alkenyl substituted pyridoxine derivatives has been developed. A series of 31 novel alkenyl pyridoxine derivatives, stilbene-based bioisosteric analogs of estradiol, were synthesized. In vitro cytotoxicity of the obtained compounds against MCF-7 (ER+) breast cancer tumor cells was studied using the MTT assay. The most active compounds with IC 50, MCF-7 < 10 μM were also tested for cytotoxicity in vitro against MDA-MB-231 (ER-) breast adenocarcinoma cells and conditionally normal human skin fibroblasts (HSF). The patterns of structure-antitumor activity relationships of the obtained compounds were analyzed. The most active compounds were found to contain a six-membered ketal ring, a methyl group in position 5, a 3,4-dimethoxystyryl fragment in positions 2 or 6 of the pyridoxine ring, and a trans-configuration of the double bond. Using the most active compound 5a as a representative cytotoxic agent, we have demonstrated that it has high specificity and antiproliferative activity against MCF-7 (ER+) tumor cells (IC 50 < 5 μM), and a higher therapeutic index compared to the reference compound raloxifene (48 versus 5.8). Compound 5a decreased the mitochondrial membrane potential and increased the level of reactive oxygen species in MCF-7 cells, but not MDA-MB-231 cells. Compound 5a did not affect the distribution of cell cycle phases and induced apoptosis in MCF-7 cells, but not MDA-MB-231. Unlike compound 5a , raloxifene decreased mitochondrial potential, increased the ROS level, and induced apoptosis in both MCF-7 and MDA-MB-231 cells, which indicated a lack of selectivity for cells with estrogen receptor expression. It was also shown that compound 5a reduced the level of ERα expression in cells to a lesser extent than raloxifene and, unlike the latter, did not activate the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]