R. Z. Musin

Synthesis and antibacterial activity of novel phosphonium salts on the basis of pyridoxine.

A series of 13 phosphonium salts on the basis of pyridoxine derivatives were synthesized and their antibacterial activity against clinically relevant strains was tested in vitro. All compounds were almost inactive against gram-negative bacteria and exhibited structure-dependent activity against gram-positive bacteria. A crucial role of ketal protection group in phosphonium salts for their antibacterial properties was demonstrated. Among synthesized compounds 5,6-bis[triphenylphosphonio(methyl)]-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine dichloride (compound 20) was found to be the most effective towards Staphylococcus aureus and Staphylococcus epidermidis strains (MIC 5μg/ml). The mechanism of antibacterial activity of this compound probably involves cell penetration and interaction with genomic and plasmid DNA.

Bis-phosphonium salts of pyridoxine: the relationship between structure and antibacterial activity.

A series of 23 novel bis-phosphonium salts based on pyridoxine were synthesized and their antibacterial activities were evaluated in vitro. All compounds were inactive against gram-negative bacteria and exhibited the structure-dependent activity against gram-positive bacteria. The antibacterial activity enhanced with the increase in chain length at acetal carbon atom in the order n-Pr>Et>Me. Further increasing of length and branching of alkyl chain leads to the reduction of antibacterial activity. Replacement of the phenyl substituents at the phosphorus atoms in 5,6-bis(triphenylphosphonio(methyl))-2,2,8-trimethyl-4H-[1,3]-dioxino[4,5-c]pyridine dichloride (compound 1) with n-butyl, m-tolyl or p-tolyl as well as chloride anions in the compound 1 with bromides (compound 14a) increased the activity against Staphylococcus aureus and Staphylococcus epidermidis up to 5 times (MICs=1-1.25 μg/ml). But in practically all cases chemical modifications of compound 1 led to the increase of its toxicity for HEK-293 cells. The only exception is compound 5,6-bis[tributylphosphonio(methyl)]-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine dichloride (10a) which demonstrated lower MIC values against S. aureus and S. epidermidis (1 μg/ml) and lower cytotoxicity on HEK-293 cells (CC(50)=200 μg/ml). Compound 10a had no significant mutagenic and genotoxic effects and was selected for further evaluation. It should be noted that all bis-phosphonium salt based on pyridoxine were much more toxic than vancomycin.

Synthesis and anti-tuberculous activity of diesters based on isosteviol and dicarboxylic acids

Diesters based on isosteviol and dicarboxylic acids were synthesized and tested for antituberculous activity. Isosteviol and some of its derivatives exhibit appreciable tuberculostatic properties in vitro, the activity being dependent on the length of the polymethylene spacer connecting two ent-beyeran fragments. The mechanism of the antituberculous action of isosteviol derivatives are discussed.

New synthesis of diterpenoid (16S)-dihydrosteviol

A new procedure has been developed for the synthesis of diterpenoid (16S)-dihydrosteviol [(16S)-13-hydroxy-ent-kauran-19-oic acid] by acid hydrolysis (0.7% hydrochloric acid) of SWETA food sweetener and subsequent reduction of the resulting mixture of caurenoids with hydrazine hydrate over Raney nickel. The molecular geometry of (16S)-dihydrosteviol, as well as of Δ15-steviol (13-hydroxy-ent-kaur-15-en-19-oic acid), was determined for the first time by X-ray analysis.

Development of synthetic approaches to macrocyclic glycoterpenoids on the basis of glucuronic acid and diterpenoid isosteviol

An approach has been developed to the synthesis of macrocyclic glycoterpenoids containing diterpenoid isosteviol and glucuronic acid fragments. Selective screening revealed compounds exhibiting antitubercular activity against H37RV, M. Avium, and M. Terrae strains at a level comparable to the known antitubercular drugs isoniazid, ofloxacin, and pyrazinamide. The compound possessing the highest antitubercular activity is non-cytotoxic toward human erythrocytes.

Study of “Racemic Compound-Like” Behavior of Diastereomeric Mixture of Pinanyl Sulfoxides by X-Ray Diffraction, IR Spectroscopy, and DFT Calculations

Abstract The oxidation of a β-hydroxysulfide in the pinane series by use of m-chloroperbenzoic acid resulted in the formation of the corresponding β-hydroxysulfoxide as a mixture of two diastereomers in 4:5 ratio. According to single-crystal X-ray diffraction (XRD) results, it is established that the diastereomeric mixture of sulfoxides crystallizes in the “racemic compound-like” manner under formation of asymmetric dimers through S=O··H–O interactions. This asymmetric dimer formed from diastereomeric molecules is a structural unit in both crystal modifications, the triclinic and the monoclinic one. The behavior of the diastereomeric mixture of pinane derived sulfoxides in crystals, melts and in tetrachloromethane solutions was studied by IR spectroscopy. The density functional theory (DFT) method with 6-31G (d, p) basis set was used to calculate the optimized geometrical parameters and vibrational frequencies of different associates in solutions. The calculated vibrational frequencies are compared with experimental IR spectra. GRAPHICAL ABSTRACT

TETRAPHOSPHORUS TRISULFIDE IN REACTIONS WITH THIOACETALS, AMINALS, SULFENAMIDES AND DISULFIDES. INFLUENCE OF AMINES AND BENZOYL PEROXIDE

Abstract The reactions of tetraphosphorus trisulfide with thioacetals, aminals, sulfenamides and disulfides were studied. The reactions were found to give organothiophosphorus compounds and to be facilitated by organic amines and benzoyl peroxide.

Facile and Convenient Synthesis of Functionalized Aryl-Containing Isoindigo Derivatives via Substituted Indolin-2-one Carbene Dimerization

Abstract The reaction of substituted benzyl-, aroylmethyl-, or 1-phenetylisatins with hexaethyltriaminophosphine has been shown to lead to the formation of a library of 3,3′-biindolinylidene-2,2′-diones with functionalized benzyl-, aroylmethyl-, and 1-phenetyl fragments at the nitrogen atom. GRAPHICAL ABSTRACT

Formation of the cage-like phosphoranes with the P-C and P-N bonds in the reactions of 2-(2-benzylidenamino)phenoxy-4- tert -butylbenzo-1,3,2-dioxaphosphol with ethyl mesoxalate and ethyl trifluoropyruvate

The reaction of 2-(2-benzylidenamino)phenoxy-4-tert-butylbenzo-1,3,2-dioxaphosphol with ethyl mesoxalate and ethyl trifluoropyruvate resulted in the formation of tricyclic phosphoranes with the P-C and P-N bonds. The adduct emerged from the initial reaction of the PIII derivative with the activated ketone (1: 1), further underwent the transformation via the intramolecular reaction involving the benzylideniminoaryl substituent, which resulted in the formation of the cage-like phosphoranes.

Synthesis of macrocycles with one and more ent-beyerane skeletons based on the diterpenoid isosteviol

Macrocycles with one and more ent-beyerane skeletons were prepared by the reaction of 16,19-dihydroxyent-beyerane with several dibasic carboxylic acid chlorides. The structures of the synthesized compounds, namely, the number of ent-beyerane skeletons in the macrocycle, depended on the length of the polymethylene chain in the acid chloride. The molecular structures of two of the synthesized macrocycles were establishedby x-ray crystal structures.