Electrochemical hydrocarboxylation of enol derivatives with CO2: access to ß-acetoxycarboxylic acids.

Electrochemical hydrocarboxylation of enol acetates with CO2 is developed. The disclosed process provides ß-acetoxycarboxylic acids in 25-66% yields, in contrast to the electrolysis of ketones, silyl enol ethers and vinyl tosylates with CO2, which leads mainly to alcohols.

Secosteroid thiosemicarbazides and secosteroid-1,2,4-triazoles as antiproliferative agents targeting breast cancer cells: Synthesis and biological evaluation.

A convenient and selective approach to 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N'-arylcarbothioamido]hydrazides and hybrid molecules containing secosteroid and 1,2,4-triazole fragments was disclosed and these novel types of secosteroids were screened for cytotoxicity against hormone-dependent human breast cancer cell line MCF-7. Most of secosteroid-1,2,4-triazole hybrids showed significant cytotoxic effect comparable or superior to that of the reference drug cisplatin. Hit secosteroid-1,2,4-triazole hybrids 4b and 4h were characterized by high cytotoxicity and good selectivity towards MCF-7 breast cancer cells. PARP cleavage (marker of apoptosis) and ERα and cyclin D1 downregulation were discovered in MCF-7 cells treated with lead secosteroid-1,2,4-triazole hybrid 4b. The synthesized secosteroids may be considered as new promising anticancer agents.

Heterogeneous Photocatalysis as a Potent Tool for Organic Synthesis: Cross-Dehydrogenative C-C Coupling of N-Heterocycles with Ethers Employing TiO2/N-Hydroxyphthalimide System under Visible Light.

Despite the obvious advantages of heterogeneous photocatalysts (availability, stability, recyclability, the ease of separation from products and safety) their application in organic synthesis faces serious challenges: generally low efficiency and selectivity compared to homogeneous photocatalytic systems. The development of strategies for improving the catalytic properties of semiconductor materials is the key to their introduction into organic synthesis. In the present work, a hybrid photocatalytic system involving both heterogeneous catalyst (TiO2) and homogeneous organocatalyst (N-hydroxyphthalimide, NHPI) was proposed for the cross-dehydrogenative C-C coupling of electron-deficient N-heterocycles with ethers employing t-BuOOH as the terminal oxidant. It should be noted that each of the catalysts is completely ineffective when used separately under visible light in this transformation. The occurrence of visible light absorption upon the interaction of NHPI with the TiO2 surface and the generation of reactive phthalimide-N-oxyl (PINO) radicals upon irradiation with visible light are considered to be the main factors determining the high catalytic efficiency. The proposed method is suitable for the coupling of π-deficient pyridine, quinoline, pyrazine, and quinoxaline heteroarenes with various non-activated ethers.

Secosteroid-quinoline hybrids as new anticancer agents.

An elegant approach to unknown secosteroid-quinoline hybrids is disclosed. A series of 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N'-(iso)quinolylmethylene]hydrazides was prepared and these novel type of secosteroids was screened for antiproliferative activity against estrogen-responsive human breast cancer cell line MCF-7. Most of the synthesized compounds showed a cytotoxic effect superior to that of reference drug cisplatin; the lead compound exhibits the highest activity with the IC50 value of about 0.8 µM and is 7 times more active than cisplatin. A high selectivity index was observed for the hit 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N'-quinolylmethylene]hydrazides 2a and 2c. Compounds 2a and 2c evaluated in luciferase reporter assays exhibited high antiestrogenic potency which was superior to that of tamoxifen. These hit compounds were characterized by high activity against MCF-7 cells that retained towards multidrug-resistant NCI/ADR-RES cells.

Secosteroidal hydrazides: Promising scaffolds for anti-breast cancer agents.

A convenient and selective approach to 13,17-secoestra-1,3,5(10)-trien-17-oic acid hydrazides and their N'-(het)arylmethylene derivatives was disclosed and these novel types of secosteroids were screened for cytotoxicity against hormone-dependent human breast cancer cell line MCF-7. A number of 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N'-(het)arylmethylene]hydrazides show significant cytotoxic effect comparable or superior to that for reference drug cisplatin. Compound 3l exhibits the highest activity with the IC50 value of about 2 µM and is 2.8 times more active than cisplatin. Hit 13,17-secoestra-1,3,5(10)-trien-17-oic acid [N'-(het)arylmethylene]hydrazides 3d, 3l and 3q are characterized by high cytotoxicity and good selectivity towards MCF-7 breast cancer cells. The synthesized secosteroids may be considered as new promising antitumor agents.

Electrochemical Synthesis of Fluorinated Ketones from Enol Acetates and Sodium Perfluoroalkyl Sulfinates.

The electrochemical synthesis of fluorinated ketones from enol acetates and RfSO2Na in an undivided cell under constant current conditions was developed. The electrosynthesis proceeded via perfluoroalkyl radical generation from sodium perfluoroalkyl sulfinate followed by addition to the enol acetate and transformation of the resulting C radical to a fluorinated ketone. The method is applicable to a wide range of enol acetates and results in the desired products in yields of 20 to 85%.

Electrochemically induced multicomponent assembling of isatins, 4-hydroxyquinolin-2(1H)-one and malononitrile: a convenient and efficient way to functionalized spirocyclic [indole-3,4'-pyrano[3,2-c]quinoline] scaffold.

Electrochemically induced catalytic multicomponent transformation of isatins, 4-hydroxyquinolin-2(1H)-one and malononitrile in ethanol in an undivided cell in the presence of sodium bromide as an electrolyte results in the formation of spirooxindoles with fused functionalized indole-3,4'-pyrano[3,2-c]quinoline] scaffold in 75-91% substance yields and 500-600% current yield. The developed efficient electrocatalytic approach to medicinally relevant [indole-3,4'-pyrano[3,2-c]quinoline] scaffold is beneficial from the viewpoint of diversity-oriented large-scale processes and represents a novel example of facile environmentally benign synthetic concept for electrocatalytic multicomponent reactions.