E. I. Chernoburova

A Straightforward Approach toward Multifunctionalized Pyridazines via Imination/Electrocyclization

A facile synthesis of functionalized 3-carbamide pyridazines starting from readily available chlorovinyl aldehydes and oxamic acid thiohydrazides via cascade imination/electrocyclization is reported. In the presence of p-toluenesulfuric acid, various ketones have been efficiently incorporated into the pyridazine derivatives through a two-step sequence involving a Vilsmeier-Haack reaction and imination. The synthetic value of this method has been demonstrated by efficient synthesis of steroidal pyridazines.

Synthesis and biological activity of new avermectin 5-O- and 4″-O-acyl derivatives

Acylation of avermectin B1 with vicinal 1,2-dicarboxylic acid anhydrides leads only to 5-O-acyl derivatives in high yields. Avermectin 4″-O-acyl derivatives were obtained under similar conditions from avermectin B1 5-O-TBS-derivatives in good yields. The compounds obtained are of interest as antiparasitic agents.

Access to steroidal pyridazines via modified thiohydrazides

An approach to steroids annulated with pyridazines via cascade imination/electrocyclization of chlorovinyl aldehydes with oxamic acid thiohydrazides is disclosed. A mechanistic rationalization was performed using real-time 1H NMR spectroscopy and computational studies. A series of 18-nor-5α-androsta-2,13-diene[3,2-d]pyridazines, androsta-2-ene[3,2-d]pyridazines and Δ1,3,5(10)-estratrieno[16,17-d]pyridazines were synthesized from native hormones. These compounds were screened for cytotoxicity against the human estrogen-responsive breast cancer cell line MCF-7 and the estrogen-independent breast cancer cell line MDA-MB-231. The structure–activity relationship analysis revealed that the annulation of the pyridazine moiety to the A-ring of the 17β-hydroxy-5α-androsta-2-ene core provides high antiproliferative activity. Compounds 7a and 10b exhibited higher antiproliferative potency than the drug cisplatin. 5α-Androsta-2-ene[3,2-d]pyridazine 10c showed good selectivity against the MCF-7 breast cancer cells.

Effect of ω-substituents in the hydrazones of conjugated pregnane 20-ketosteroids on their ability to cyclize to pyrazolines

The reactions of 3β-acetoxy-5-pregnan-20-one with thiooxamic acid hydrazides were studied. Depending on the nature of substituents in the thiohydrazide, the reactions give the corresponding hydrazones or pyrazolines resulting from hydrazone cyclization.

Synthesis of thieno[2,3-d]pyrimidine and quinazoline derivatives from monothiooxamides

A method for syntheses of previously unknown derivatives of thieno[2,3-d]pyrimidines and quinazolines from monothiooxamides was proposed.

Synthesis of Carbamoyl-Containing N,S-Heterocyclic Compounds

Monothioxamides unsubstituted at the thioamidic nitrogen atom were obtained by the reaction of NS-morpholino-NO-R-thioxamides with ammonia. Carbamoyl-containing 5-phenylcarbamoyl-1,2,4-dithiazoles, 6-phenylcarbamoyl-5,6-dihydro-[1,2,4,5]-dithiadiazin-3-one, and 5-phenylcarbamoyl-2-oxy-1,3,4-thiadiazole were synthesized by the reaction of monothioxamides or thiohydrazides of oxamic acids with chlorocarbonylsulfenyl chloride.

Synthesis of esters of bile acids and avermectin B1

Esters of bile acids and avermectin B1 were obtained for the first time by the reaction of avermectin B1 with bile acid anhydrides.

Synthesis of 5,4″-di-O-succinoylavermectin B1

A reaction of avermectin B1 with succinic anhydride at ultrahigh pressure (10 kbar) gave previously unavailable 5,4″-di-O-succinoylavermectin B1, which is of interest as potential antiparasitic agent.

Reaction of 5- O -succinoylavermectin B 1 with alkylating agents

A reaction of 5-O-succinoylavermectin B1 with alkylating agents, namely phenacyl halides, bromoacetanilides, and benzyl bromides, was studied. Esters of 5-O-succinoylavermectin B1 were obtained for the first time, which are of interest as potential antiparasitic agents.

Interaction of 16-hydroxymethylidene derivatives of androstane and estrone with thiohydrazides of oxamic acids

Reaction of thiohydrazides of oxamic acids with 16-hydroxymethylidene derivatives of androstane and estrone involves the hydroxymethylidene group and leads to thiohydrazones, which undergo heterocyclization to give 16-(1,3,4-thiadiazol-2-yl)-substituted steroids.