Thioxo Compounds Research Articles

Amino acid ionic liquid-catalyzed synthesis, anti-Leishmania activity, molecular docking, molecular dynamic simulation, and ADME study of 3,4-dihydropyrimidin-2(1H)-(thio)ones

The synthesis of 3,4-dihydropyrimidin-2(1H)-(thio)one (DHPM) derivatives involving aromatic aldehyde, β-ketoesters and urea/thiourea using prolinium hydrogen sulfate (ProHSO4) as a catalyst has been studied. A variety of DHPM derivatives were obtained in high yield under solvent-free conditions in a short reaction time. The in-vitro screening of antileishmanial activity of both the oxo and the thioxo compounds showed significant activity against extracellular promastigotes. The aldehyde substituted at C-4 position with methyl (4g) in the oxo series and chloro (4m), methyl (4n) in the thioxo series imparted good bioactivity, with >80% reduction in viability at 50 µg/mL, with IC50 values 29.3, 29.3, and 28.3 µg/mL, respectively. Molecular docking study of the compound 4m displayed −6.4 kcal/mol binding energy. According to 50 ns molecular dynamics simulation study Leishmania major pteridine reductase 1 (PTR1) interacts well with the amino acid residues Phe-109, Leu-222, and Val-226. The in silico ADME study showed good drug-likeness properties.

Nickel Boride

Nickel boride (Ni2B), first reported in the pioneering work of Schlezinger and Brown [¹] and traditionally used as a catalyst for hydrogenation, [²] has more recently found a niche as a reducing agent in its own right. [³] Its ease of preparation, handling, and versatility as a reducing agent promise nickel boride its deserved attention from academic and industrial sectors. Nickel boride has been employed for a wide range of transformations including reductive dehalogenation of organic halides [4] , reductive amination of carbonyl compounds, [5] desulfurization of a variety of thioxo compounds, [6] deoxygenation of sulfoxides and selenoxides, [7] and reducing of nitrogen functionalities. [8] Of late, the reagent is being explored in the form of a nickel boride silica nanocomposite catalyst for hydrogen production from NaBH4 hydrolysis. [9]

ChemInform Abstract: Reactions of Thioxo Compounds with N-Chloroamides. Part 5. Zwitterionic N,N′-Bis(phenylsulfonyl)sulfodiimidate with a Carbocyclic Cationic Moiety.

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Photoswitchable Elements within a Peptide BackboneUltrafast Spectroscopy of Thioxylated Amides

A series of thioxo compounds, thioacetamide, N-methylthioacetamide, a cyclic thioxoamide [(S)-5-thioxopyrrolidine-2-carboxylic acid ethyl ester], two thioxylated dipeptides (Ala-Psi[CS-NH]-Ala and Phe-Psi[CS-NH]-Ala) and a thioxylated dodecapeptide (Lys-Glu-Thr-Ala-Ala-Ala-Lys-Phe-Glu-Arg-Gln-His-Psi[CS-NH]-Nle-Asp-Ser-Ser-Thr-Ser-Ala-Ala, or [thioxo-His(12)]-S-peptide; Nle = norleucine) are investigated by ultrafast spectroscopy in the visible and near UV. The different molecules show very similar absorption dynamics featuring a rise of a strong visible absorption band on the subpicosecond and picosecond time scale. The decay of the visible absorption occurs within 150-600 ps. The observations are interpreted by the ultrafast formation of triplet states and their decay on the subnanosecond time scale. Comparison with published IR experiments on N-methylthioacetamide indicates that the cis-trans isomerization around the thioxopeptide bond is terminated within less than 1 ns.

Synthesis of new heterocondensed pteridines

AbstractReaction of 2‐aminopyrazine 1 with isothiocyanate, isocyanate or dithioketal reagent furnished pteridines 3,4 in good yield. Thioxo compound 3a was chlorinated, methylated and subsequently displaced by amines. A simple one‐step synthesis of heterocondensed pteridines 8–13 by reaction of 2‐aminopyrazine with various imino thioacetals was described 8–13.

Cycloadditions of `Thiocarbonyl Ylides' with Tetracyanoethylene (=Ethenetetracarbonitrile): Interception of Intermediates

Thiocarbonyl ylides (=sulfonium ylides) belong to the most nucleophilic 1,3-dipoles (high HO energy). In their reactions with tetracyanoethylene (TCNE=ethenetetracarbonitrile; low LU energy), a borderline crossing from the concerted mechanism to a two-step pathway via a 1,5-zwitterion was observed. Steric hindrance at one or both termini of the 1,3-dipole is an additional requirement. The ylides 3 and 13, set free by N2 elimination of dihydro-1,3,4-thiadiazoles, underwent electrocyclization or 1,4-H shift. Ylides 3 and 13 are bases and afforded MeOH adducts of different regiochemistry. Whereas 3 and TCNE in abs. THF at 45° furnished the (3+2) cycloadduct 20, a MeOH content of 0.5 – 5 vol-% in THF gave rise to a seven-membered lactim ether 22 and thiolane 20 in a 65: 35 ratio (Scheme 4). Water (0.5 – 1 vol-%) in THF led to lactam 24 and adduct 20 in the same ratio. The zwitterion 26, assumed to be the first intermediate, enters competing reactions: the irreversible ring closure to thiolane 20 and the reversible formation of a strained, cyclic seven-membered `ketene imine' 28, which is intercepted by MeOH or H2O. The gauche-conformation 32 of an analogous zwitterion, produced from the tetrasubstituted `thiocarbonyl ylide' 13 with TCNE (Scheme 5), led to the thiolane derivative 35, while the anti-conformation 33 afforded the thioxo compound 5 and cyclopropane derivative 36 by intramolecular nucleophilic substitution.

Synthesis and antiviral activity of benzyl-substituted imidazo [1,5-a]-1,3,5-triazine (5,8-diaza-7,9-dideazapurine) derivatives.

A variety of imidazo[1,5-a]-1,3,5-triazine derivatives carrying C-, O-, and S-benzyl and/or 4-methylbenzyl groups were synthesized and examined for their inhibitory effects on the replication of ortho- and paramyxoviruses. The key compounds 8-R-2-thioxo-2,3-dihydroimidazo [1,5-a]-1,3,5-triazin-4(1H)-ones 3a,b,d were synthesized by chlorotrimethylsilane/HMDS-effected cyclization--rearrangement of the corresponding 6-amino-5-(formylamino)-5-R-2-mercaptopyrimidin-4(5H)-ones 2a,b,d (R = benzyl, 4-methylbenzyl and 5-(benzyloxy)pentyl). Compounds 3a,b were further transformed into 4-thiones 5a,b and 4-dimethylamino derivatives 7a,b. Preparation of S-methyl, S-benzyl, and S-(4-methylbenzyl) derivatives 12-19 was carried out by the treatment of thioxo compounds 3b,d, 5b, and 8b in an alcohol/potassium carbonate system with methyl iodide or the appropriate aralkyl bromide. Simultaneous presence of the benzyl and thio structural units was found to be indispensable for any selective biological activity. Some 2-thio substituted compounds were specifically inhibitory to some viruses, e.g., 8-(4-methylbenzyl)-2-[(4-methylbenzyl) thio]imidazo[1,5-a]-1,3,5-triazin-4-one (13) and 8-[5-(benzyloxy)pentyl]-2-[(4-methylbenzyl)thio]imidazo [1,5-a]-1,3,5-triazin-4-one (15) inhibited influenza A virus at a concentration of 4.1 and 5.3 microM, and 2-(benzylthio)-6, 8-dimethylimidazo[1,5-a]-1,3,5-triazin-4-one (16) and 6, 8-dimethyl-2-[(4-methylbenzyl)thio]imidazo[1,5-a]1,3, 5-triazin-4-one (17) inhibited respiratory syncytial virus at a concentration of 21.9 and 15.7 microM, respectively, that is, at concentrations that were 20-50-fold lower than the cytotoxic concentrations. Compound 13 was inhibitory to respiratory syncytial virus at a concentration of 1.4 microM, that is, at a concentration that was 180-fold lower than the cytotoxic concentration to MDCK or Vero cells but only 7-fold lower than the cytotoxic concentration to HeLa cells. The 4-thiones 5a,b were nonselectively inhibitory to ortho-and paramyxoviruses at concentrations that coincided with their cytotoxic concentrations.

Synthesis of vinca alkaloids and related compounds, 73. Synthesis and ring transformations of deethylaspidospermane derivatives. Synthesis of (±)‐20‐deethyl‐3‐oxotabersonine

AbstractThe reaction of the key compound 14 with methyl 4‐formyl‐butanoate (9) or with 5‐benzoyloxypentanal (13) gave the D‐seco‐aspidospermane derivatives 17 and 18, respectively. Compound 17 was indirectly and 18 was directly converted to (±)‐20‐deethylvincadifformine (7) and (±)‐20‐deethyl‐20‐epivincadifformine (8). Epimerization occurred in both cases. The thioxo compound 23 was used for the synthesis of (±)‐20‐deethyltabersonine (28) and (±)‐20‐deethyl‐3‐oxotabersonine (27). Oxidative ring transformation of the (±)‐20‐deethylvincadifformine (7) gave (±)‐16‐deethylapovincamine (29).

ChemInform Abstract: Reaction of 1‐N‐Hydroxyethyl‐3‐iminopyrazolidine with Hexaalkylphosphorous Triamide.

AbstractReaction of the title compounds (I) and (II) yields the oxadiazaphosphorinanes (III) which are treated with sulfur, producing the thioxo compounds (IV).

ChemInform Abstract: PHOTOCHEMICAL REACTION OF SOME AROMATIC THIONES WITH ARYL‐ AND ALKYL‐SUBSTITUTED (METHYLTHIO)ACETYLENES. THE (2 + 2)‐CYCLOADDITION PRODUCTS AND THE OCCURRENCE OF THE EQUILIBRIUM THIETE ⇌ α,β‐UNSATURATED THIOXO COMPOUND

AbstractDie Thione (Ia) bzw. (Ib) reagieren mit der Dreifachbindung der Acetylene (IV) bei Bestrahlung in nicht regiospezifischer Weise zu den Additionsprodukten (II)+(III) bzw. (V) + (VI); mit dem.

Photochemical reaction of some aromatic thiones with aryl‐ and alkyl‐substituted (methylthio)acetylenes. The (2+2)‐cycloaddition products and the occurrence of the equilibrium thiete ⇋ α, β‐unsaturated thioxo compound

AbstractUpon irradiation (λ > 525 nm), xanthenethione 2o and thioxanthenethione 2s react in a non‐regiospecific manner with the triple bond of the acetylenes 6a (Ph‐C≡C‐SCH3) and 6b [(2‐thienyl)–C≡C‐SCH3] to produce in each case the two possible (2 + 2)‐cycloaddition products, which were isolated as thietes or α,β‐unsaturated thioxo compounds. In a solution of each of these reaction products, spectroscopic results confirmed the occurrence of the equilibrium thiete ⇋ α, β‐unsaturated thioxo compound. With acetylene 6c (t‐Bu‐C≡C‐SCH3), the photochemically excited thiones 2o and 2s gave, in each case, only the (2 + 2)‐cycloaddition product 8. In solution these thietes 8 do not equilibrate with the corresponding α, β‐unsaturated thiones. Surprisingly, no products could be isolated or detected after irradiation of thiobenzophenone 2h in the presence of acetylenes 6a or 6b.