M. Kh. Dzhafarov

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.

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.

SYNTHESIS OF 1,2,4-SUBSTITUTED HEXAHYDROPYRIDAZINES AND X-RAY STRUCTURAL INVESTIGATION OF 4-HYDROXYIMINO-2-METHYL-1-PHENETHYLHEXAHYDROPYRIDAZINE

A series of new 1,2,4-substituted hexahydropyridazines was prepared in order to evaluate qualitatively and quantitatively the role and influence of substituents on the biological activity of this system. An X-ray structural investigation of 4-hydroxyimino-2-methyl-1-phenethylhexahydropyridazine was performed. The compounds considered exhibit moderate local anesthetic, antihistaminic, and anticonvulsive activity.

Synthesis of sodium 5-sulfate-ivermectin and disodium 4″,5-disulfate-ivermectin

Treatment of ivermectin with sulfuric acid–acetic anhydride in pyridine gives sodium 5-sulfate-ivermectin and disodium 4″,5-disulfate-ivermectin. The synthesized salts are water-soluble compounds with promising antiparasitic activity.

Synthesis of ivermectin-4″,5-diyl[bis(N-methylcarbamate)]

New ivermectin-4″,5-diyl[bis(N-methylcarbamate)] was synthesized by the MoO2Cl2(DMF)2-catalyzed reaction of ivermectin with methyl isocyanate. The synthesized compound could find application as antiparasitic agent.

Functionalization of NH-unsubstituted androstano[17,16-d]pyrazoles. Synthesis of 2-arylamino-2-thioxoacetylandrostano[17,16-d]pyrazoles

An approach to the synthesis of earlier unknown androstano[17,16-d]pyrazoles containing a monothiooxamide fragment at the nitrogen atom of the pyrazole ring has been suggested. The method is based on the reaction of NH-unsubstituted androstano[17,16-d]pyrazole with chloroacetyl chloride with subsequent involvement of the obtained N-chloroacetylpyrazole into the reaction with elementary sulfur in the presence of aromatic amines. The synthesized androstano[17,16-d]pyrazoles containing a monothiooxamide fragment at the nitrogen atom of the pyrazole ring exhibit high antiparasitic activity.

New variants in the total synthesis of 14?-hydroxy-17?,R-8?,9?-estradiol derivatives

Two procedures were developed for the synthesis of 17α-alkyl-8α,9β-estra-1,3,5(10)-triene-3,14β,17β-triols from 3-methoxy-estra-1,3,5(10),8(9),14(15)-pentaene-17-one (1) using photosensitized oxidation by atmospheric oxygen or ionic hydrogenation in the presence of oxygen. It was shown that 17α-hexynyl-8α,9β-estra-1,3,5(10)-triene-3,14β,17β-triol (23) and its 3-methoxy derivative (26) inhibit K+,Na+-ATPase, with inhibition degree increasing on introduction of an oxygen-containing substituent into position 17. For the first time steroids were found with α2-adrenoblocking action.

Isomerization of 14-hydroxy-17-ketosteroids: New examples of two-centered inversion of the C/D ring fusion and X-ray diffraction structural analysis of d,ℓ-3-methoxy-14β-hydroxy-8β, 9α-estra-1,3,5(10)-trien-17-one

Abstractd,ℓ-3-Methoxy-14β-hydroxy-8α,9β-estra-1,3,5(10)-trien-17-one (I) undergoes two-centered isomerization in alkaline medium to d,ℓ-3-methoxy-14β-hydroxy-8β,9α-estra-1, 3,5(10)-trien-17-one (II) in 70% yield. Under analogous conditions, natural isomer (II) is converted into synthetic isomer (I) in 20% yield. The crystalline and molecular structure of isomer (II) was established.