Synthesis and pharmacological properties 4-methyl-1-(methylsulfinylmethyl)-7-thiabicyclo[3.3.1]non-3-en-2-one-7-oxide

Abstract

Some representatives of the class of sulfur-containing organic compounds, including derivatives of sulfones [1], dialkyldisulfides [2], and 3-thiabicyclohexanecarboxylic acid [3], were reported to possess anti-inflammatory activity. Biological activity is also inherent in 1,2,5-thiadiazole and its condensed derivatives, which act upon central nervous system and influence tissue metabolism [4].In continuation of our investigations into new bicyclic bis-sulfoxides, we have synthesized 4-methyl-1-(methylsulfinylmethyl)-7-thiabicyclo[3.3.1]non-3-en-2-one-7-oxide (I) and studied the anti-inflammatory and antiarrhythmic properties of this compound.The synthesis I was conducted according to the scheme depicted below. In the first step, we obtained 4-methyl-1-(methylthiomethyl)-7-thiabicyclo[3.3.1]non-3-en-2-one (II) via alkylthiomethylation of propanone with a mixture of formaldehyde, methylmercaptan, and sodium sulfide in an alkaline medium [5]. In the second step, compound II was oxidized in a 28 -30% aqueous hydrogen peroxide solution at 20°C, and the target compound I was obtained with a yield of 95%.The purity and the proposed structures of the synthesized compounds were confirmed by the results of elemental analyses and by the data of IR, 1 H NMR, and 13 C NMR spectroscopy (Tables 1 and 2). The IR spectra of compounds I and II exhibit absorption bands at 1656, 1618, 1624, and 1654 cm -1 characteristic of the stretching vibrations of the C=O and C=C bonds [6].In the 13 C NMR spectrum of compound I, the signals from carbon atoms C 6 (48.43 and 48.54 ppm), C 8 (56.75 and 56.06 ppm), C 11 (62.62 and 61.52 ppm), and C 13 (36.08 and 35.79 ppm) are shifted toward lower fields as compared to the analogous signals in the spectrum of compound II (Table 2). In addition, almost all signals in the 13 C NMR spectrum of compound I are doubled, which is indicative of the existence of two isomers. The spectra were assigned separately to each isomer. The appearance of a diastereomer pair is related to the presence of a chiral carbon atoms C 1 and a pyramidal sulfoxide sulfur atom in the aliphatic substituent, which make possible the formation of two d-diastereomers with R*R* and R*S* centers [7].The 1 H C NMR spectrum of compound I displays clearly distinguished signals due to the greater isomer and shows the signals from diastereotopic protons at C 11 in the form of two doublets with a geminal spin -spin coupling constant of 13.3 Hz and a relative chemical shift Dd = 0.61 ppm. For the second diastereomer, this difference is below 0.29 ppm. Based on the published data [7], the diastereomer with a greater difference of the chemical shifts is identified as the erythro isomer (Ia), while the component with a smaller Dd value is identified as the threo isomer (Ib). Both isomers are 659

Catalyst-Free Oxidation of Sulfides to Sulfoxides by gem-Dihydroperoxide under Mild Conditions

“…17 In the case of a sulfide with a pyrazole substituent, a sulfoxide is also formed in good yield; no oxidation products at nitrogen atoms were found. Disulfide 13 (Scheme 4 ) is oxidized by 1a with the formation of bis-sulfoxide (it has antiarrhythmic activity) 18a as at the equimolar ratio of the reactants and with an excess of substrate of 1:2. The bis-sulfoxide precipitates as colorless needles from benzene during the reaction.…”

Oxidation and reduction of 1,1′-[3-(methylsulfanylmethyl)tetrahydro-2H-thiopyran-3,5-diyl]diethanone

“…Reactions of the title compound with sodium tetrahydridoborate and hydroxylamine hydrochloride afforded mono-and dihydroxy derivatives and monooxime, respectively.Four-component condensation of acetone with formaldehyde and sodium sulfide and methanethiolate that are components of alkaline sulfide solutions at gas processing plants was used to develop convenient procedures for the preparation of 1,1′-[3-(methylsulfanylmethyl)tetrahydro-2H-thiopyran-3,5-diyl]diethanone (I) and 8-methyl-5-(methylsulfanylmethyl)-3-thiabicyclo[3.3.1]non-7-en-6-one [1, 2] as promising starting compounds in the synthesis of polyfunctional heterocycles [3,4], including those possessing biological activity [5].In the present work we studied oxidation of the sulfur atoms and reduction and oximation of the oxo groups in 1,1′-[3-(methylsulfanylmethyl)tetrahydro-2H-thiopyran-3,5-diyl]diethanone (I). Oxidation of compound I to sulfoxide under conditions of potentiometric iodatometry [6] revealed nonequivalence of the sulfur atoms in I with respect to the oxidant.…”

“…Four-component condensation of acetone with formaldehyde and sodium sulfide and methanethiolate that are components of alkaline sulfide solutions at gas processing plants was used to develop convenient procedures for the preparation of 1,1′-[3-(methylsulfanylmethyl)tetrahydro-2H-thiopyran-3,5-diyl]diethanone (I) and 8-methyl-5-(methylsulfanylmethyl)-3-thiabicyclo[3.3.1]non-7-en-6-one [1,2] as promising starting compounds in the synthesis of polyfunctional heterocycles [3,4], including those possessing biological activity [5].…”