S. N. Morozkina

A one-pot synthesis of 1-arylalka-1,3-diynes by sequential acetylene zipper and Sonogashira reactions

1,3-Diynes, formed in situ by base-induced acetylene zipper reactions, following anion quenching with water, undergo smooth Sonogashira-type couplings with functionalized aryl iodides, to give good overall yields of 1-arylalka-1,3-diynes.

Concentration dependent switch from addition to substitution in the reaction between salicylaldoxime and a nitrile platinum(IV) complex

Abstract The nitrile complex [Ph3PCH2Ph][PtCl5(EtCN)] reacts with one equivalent of salicylaldoxime, HONCH(C6H4OH-o), in CH2Cl2 to afford mainly the addition product [Ph3PCH2Ph][PtCl5{NHC(Et)ONCH(C6H4OH-o)}] (1). In a diluted solution, i.e. if the same amount of the reagents is dissolved in 50-fold volume of dichloromethane, the four platinum-containing species, i.e. 1, [Ph3PCH2Ph][PtCl4{C6H4(O)C(H)NOH}] (2) [Ph3PCH2Ph][PtCl5(NH3)] (3), and [Ph3PCH2Ph]2[PtCl6] (4), are formed and the substitution compound 2 is the major product at low concentrations. Addition of EtCN to the less concentrated solution suppresses the formation of the substitution product 2 and moves the reaction back towards formation of the addition product 1. The complex 1 is unstable in non-dried solutions and decomposes to give 2 along with 3, 4 and EtCO2H. Compounds 1, 2 and 4·1/2H2O were characterized by elemental analyses, FAB mass-spectrometry, IR and 1H, 13C{1H}, 31P{1H} and 195Pt NMR spectroscopies. X-ray structure determinations have been performed for 2 and 4·1/2H2O.

Catalytic hydrogenation on Raney nickel of estra-1,3,5(10),8,14-pentaenes with sterically accessible double bonds

The catalytic hydrogenation of estra-1,3,5(10),8,14-pentaenes with sterically accessible double bonds in the presence of Raney nickel in 2-propanol at elevated pressure and at heating to 110–120°C resulted in prevailing formation of estrogens 8α-analogs alongside a considerable quantity of estra-5,7,9-trienes. Although the hydrogenation at 45–60°C provided a higher yield of estrogens 8α-analogs, the synthesis of steroids of this group gave better results at hydrogenation in a high purity benzene.

Synthesis and Structure of Some 8α-Analogs of Steroid Estrogens

The distances between the protons of four 8α-analogues of steroid estrogens as determined by X-ray data are consistent with the calculated values obtained by ab initio, PM3 and MM+ methods, that can be used for docking of these stereochemical analogs onto α-estrogen receptors.

Molecular structure and biological properties of some 16,16-dimethyl-D-homo-B-nor-9β analogs of steroid estrogens

The interproton distances in the molecule of 17aβ-acetoxy-16,16-dimethyl-3-methoxy-D-homo-Bnor-9β-estra-1,3,5(10)-triene, determined from the X-ray diffraction data and by 1H NMR spectroscopy, were consistent with those calculated ab initio and by the PM3 and MM+ methods. Therefore, MM+ calculations were used to perform docking of a series of D-homo-B-nor-9β-estra-1,3,5(10)-trienes to hormone-binding pocket of estrogen α-receptors, and 16,16-dimethyl-D-homo-B-nor-9-estrone was selected for studying its biological properties. This compound was found to possess cardioprotective activity and no uterotropic effect.

Synthesis and biological properties of D-homo-6-oxa-8α-analogues of steroid estrogens

Modifications of D-homo-6-oxa-8α-analogues of steroid estrogens were found to lead to a complete loss of the uterotropic and hypertriglyceridemic activities. These compounds may be promising for the design on their basis of inhibitors of the steroid hormone metabolism and transporters of other compounds to the estrogen target organs.

Oxidation of Acceptor‐substituted Isothiazolium‐2‐imines to Stable Cyclic Sulfin‐ and Sulfonamides with 3‐Hydroperoxy Function

The oxidation of isothiazolium 2-imines 3,5 and their salts 4 to stable 3-hydroperoxy-2,3,4,5,6,7-hexahydro-1,2-benzisothiazole 1-oxides 7 and 1,1-dioxides 8 and 9 as a new class of cyclic sultims and sultams is described. The formation of 3-hydroxysultams 10 and isothiazol-3(2H)one 1,1-dioxides 11 is presented.

Synthesis and investigation of biological properties of modified 6-oxa-estra-1,3,5(10),8(9)-tetraenes

To investigate the relationship between structure and biological activity of analogues of steroid estrogens we have developed the synthesis of 7α-methyl-6-oxa-estra-1,3,5(10),8(9)-tetraenes with cis- and trans-junction of C and D rings. We found that such compounds have stronger osteoprotective, cholesterol-lowering and antioxidant properties in comparison with uterotrophic activity; that is the advantage in comparison with clinically used 17α-ethynylestradiol.

Synthesis and studies of structure and biological properties of D-homoanalogs of steroid estrogens

In order to estimate the potential of steroid estrogens modification, three D-homoanalogs of estrogens have been prepared; their structures and biological properties have been studied. The expansion of D-ring in such compounds has lead to strong decrease if the uterotropic action, however, the unfavorable hypertriglyceridemic effect has been retained. The latter has been eliminated by combined action of the studied steroids and ursolic acid; therewith the hypocholesterolemic activity has been retained.

“Acetylene Zipper” Reactions and Pd-Cu-Catalyzed Cross-coupling in the Synthesis of Vicinal 1,3-Alkadiynylarylamines and Aminopyridines

A preparative method was developed for vicinal-substituted 1,3-alkadiynylarylamines and aminopyridines involving a successive application of “acetylene zipper” reaction to synthesize 1,3-alkadiynes followed by Sonogashira reaction.