Synthesis of fluorine-containing functionalized isoxazolines

The reaction of regioisomeric fluoroalkyl-containing (3-aminovinylketones with hydroxylamine generatedin situ from hydroxylamine sulfate, afforded 5-hydroxy- or 5-amino-5fluoroalkyl-2-isoxazolines.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1306–1307, May,1996     

Synthesis and neurotropic activity of silyl propargyl alcohols and sulfides

New silicon derivatives of hetaryl propargyl sulfides and propargyl alcohols were synthesized using phase‐transfer catalytic and organometallic methods. These compounds were tested for acute toxicity and neurotropic activity in the pentylenetetrazole test, and for phenamine hypothermia, phenamine hyperactivity and passive avoidance response tests. We have found that the silyl propargyl alcohols and sulfides are low toxicity compounds, the LD₅₀ being 700–1300 mg kg^?1. In the PAR test, the synthesized compounds exerted some memory‐improving activity. For di‐1‐(3‐methyl‐3‐hydroxybutyn‐1‐yl)methyl(3‐iodopropyl)silane ( 16 ) the effect was statistically significant and amounted to 250% of the control level. In the pentylenetetrazole test, all compounds possessed anticonvulsant activity, the most active compounds being 3‐(benzoxazolylthio)‐1‐propynyl(trimethyl)silane ( 6 ) and di‐[2‐(1‐hydroxycyclohexyl)ethynyl]methyl(3‐iodopropyl)silane ( 17 ). The phenamine‐induced hyperactivity was significantly elevated after treatment with (3‐trimethylsilyl‐2‐propynyl)thiobenzene ( 1 ) or di‐[1‐(3‐methyl‐3‐hydroxybutyn‐1‐yl)diphenylsilane ( 12 ). Our data show that these silicon derivatives of hetaryl propargyl sulfides and propargyl alcohols possess certain memory improving and anticonvulsant activity that should be studied in detail to evaluate the receptor systems involved. Copyright © 2004 John Wiley & Sons, Ltd.     

Synthesis and pharmacological activity of diterpenylnaphthoquinone derivatives

New diterpenylquinones, combining a diterpene diacid and a naphthoquinone, were prepared from junicedric acid and lapachol. The new derivatives were assessed as gastroprotective agents by the HCl-EtOH-induced gastric lesions model in mice as well as for basal cytotoxicity on the following human cell lines: Normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), and hepatocellular carcinoma (Hep G2). Several of the new compounds were significantly active as antiulcer agents and showed selective cytotoxicity against AGS cells.     

Synthesis and pharmacological activity evaluation of curcumin derivatives

Curcumin 3,4-dihydropyrimidinones/thiones/imines have been synthesized using one-pot cyclocondensation of curcumin with substituted aromatic aldehydes and urea/thiourea/guanidine in the presence of chitosamine hydrochloride as a biodegradable and nontoxic catalyst under solvent-free microwave irradiation. The synthesized product was purified by crystallization from ethanol and the process does not involve any hazardous solvent. All the synthesized curcumin derivatives 4a-o were screened for antioxidant and anti-inflammatory activity. Biological activity data of the synthesized showed that most of the synthesized compounds exhibited greater antioxidant and anti-inflammatory activity than curcumin.     

Synthesis and pharmacological activity of the metabolites of Pratosartan

Three hydroxylated metabolites of 2-propyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one (Pratosartan), which is a selective angiotensin II receptor antagonist, were synthesized in confirmation of their structures and in studies of their pharmacological properties. An MTPA ester of the human main metabolite was identified with the synthesized compound by comparing (1)H-NMR spectra, MS spectra, and HPLC retention time. The structure of the human main metabolite was confirmed to be (S)-(-)-2-(1-hydroxypropyl)-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]-5,6,7,8-tetrahydro-3H-cycloheptimidazol-4-one ((S)-(-)-1). Also, the rat main metabolites were confirmed to be 8-hydroxylated compound (2) and 5-hydroxylated compound (3). These metabolites showed lower antagonistic activity than that of the parent compound.     

Synthesis and structure of silyl acetonitriles

An efficient route for the preparation of Mes₂HSiCH₂CN (1) and (Mes₂HSi)₂CHCN (2) is reported (Mes = 2,4,6-trimethylphenyl). Although the X-ray analyses for 1 and 2 reveal the CH_nCN functionality (n = 1, 2) to be shielded by the Mes₂HSi group, hydrolysis under basic conditions gave exclusively Mes₂HSiOH (3), as a result of hydroxide-induced Si-C bond cleavage. In the solid state 3 is a tetramer forming an eight membered ring by H-bond interactions.     

Synthesis of isoxazolines from nitrile N-oxides generated from nitroalkenes

In this review, information on the production of isoxazolines and condensed isoxazoline systems by the intramolecular 1,3-bipolar cycloaddition of unsaturated nitrile N-oxides generated in situ from nonconjugated nitroalkenes is generalized and systematized. The isoxazoline derivatives formed as the result of these reactions are promising synthons in the synthesis of various natural compounds and their analogues.Krakow Polytechnic Institute, Poland. Translated from Khimiya Prirodnykh Soedinenii, Nos. 3,4, pp. 291–305, May–August, 1992.     

Synthesis of some furochromonesulfonamide derivatives with potential pharmacological activity

A number of visnagin-9-sulfonamides 1-3 have been prepared. In two instances side-products have been isolated in which the γ-pyrone ring is opened. All compounds were characterized by high-field ¹H and ¹³C nmr and mass spectra.     

Synthesis of stable isoxazolines by [3+2] cycloaddition of oxaziridines with alkynes

N-Alkyl substituted oxaziridines undergo a [3+2] cycloaddition reaction with a variety of terminal alkynes to give the product isoxazolines, whose stability appears to depend on the electronic properties of the groups on the C-3 and C-5 positions. The presence of an electron withdrawing group on C-5 and/or an electron donating group on C-3 causes isomerization of the isoxazolines to β-amino enones.     

Synthesis and antitumor activity of 3-[(methyl)bis(5-trialkylsilyl-furan-2-yl)silyl]propylamines

Novel 3-[(methyl)bis(5-trialkylsilylfuran-2-yl)silyl]propylamines have been synthesized by a hydrosilylation reaction of aliphatic and heterocyclic N-allylamines in the presence of the Speier's catalyst. The effects of the structure of the amine and the alkyl substituent at the silicon atom on the cytotoxicity of the compounds have been studied.     

Synthesis and pharmacological activity of O-(5-isoxazolyl)-L-serine

A novel isoxazole derivative, O-(5-isoxazolyl)-L-serine (OIS, 1), was synthesized by a Mitsunobu reaction of isoxazolin-5-one (4) with N-Boc-L-serine tert-butyl ester (5) and subsequent deprotection of the coupling product. Its structure was elucidated by spectroscopic analyses. The pharmacological activity of 1 was also examined with cloned glutamate receptors and transporters using a Xenopus oocyte-expressing system showing substrate activity on an excitatory amino acid carrier 1 (EAAC 1) as a glutamate transporter.     

Synthesis of selenolates from stannyl and silyl alkylselenides

Stannyl and silyl alkylselenides have been efficiently transformed to the corresponding alkylselenolates on reaction with butyllithiums. Other conditions proved to be limited.     

Derivatives of hydroxybenzoic acids and their salts: Synthesis and pharmacological activity

Russian Journal of General Chemistry - Preparation of salicylic and acetylsalicylic acid esters via esterification and alkylation of the salts with alkyl halides has been examined. The effect of...     

Synthesis and psychotropic properties of bis(2-thenylidene)diamines and their silyl derivatives

Summary The condensation of diamines with the corresponding aldehydes gave bis(2-thenylidene)diamines and their silyl derivatives. The structure of the compounds has been confirmed by their PMR spectra. It has been shown that the introduction of the trimethylsilyl group increases the toxicity, prolongs the hexenal narcosis and the antihypoxy activity, has a positive effect on the memory processes, and has no influence on the coordination of movements, the muscle tone, and the body temperature. All compounds possess an antialcohol activity, whereby the silyl derivatives have the stronger one.Translated from Khimiya Geterotsikiicheskikh Soedinenii, No. 3, pp. 316–320, March, 1994.     

Synthesis of silyl aziridines and alpha-amino acylsilanes with silyldibromomethyllithium

The reaction of silyldibromomethyllithium with aromatic imines provides alpha-amino acylsilanes via a bromo aziridine intermediate upon quenching the reaction with water. Alternatively, treatment of the bromo aziridine intermediate with various Grignard reagents or lithium aluminum hydride permits the nucleophilic displacement of the halogen to furnish substituted silyl aziridines.     

Synthesis and pharmacological activity of 2-(biphenyl-4-yl)imidazo[1,2-a]benzimidazoles

Russian Chemical Bulletin - An efficient method for the synthesis of novel 9H-imidazo[1,2-a]benzimidazole derivatives containing a biphenyl substituent at position 2 was developed. These compounds,...     

Solid-phase synthesis of isoxazolines

The polymer-supported synthesis of isoxazolines is described via nitrile oxide intermediates, starting from primary nitroalkanes in a one-pot process.     

Synthesis of 1-hydrocarbon substituted cyclopropyl silyl ketones

The synthesis of cyclopropyl silyl ketones possessing a hydrocarbon group at 1-position of three-membered ring was investigated. The reaction of sulfoxonium ylide with α,β-unsaturated acylsilanes derived from α,β-unsaturated aldehydes did not afford the desired acylsilane derivatives. Instead, the corresponding silyl enol ethers were yielded exclusively. On the other hand, the Corey-Chaykovsky cyclopropanation of α-substituted α,β-unsaturated aldehydes proceeded well to give 1-substituted cyclopropyl aldehydes. The silyl substitution of formyl proton in the obtained aldehydes via umpolung of carbonyl group afforded the target acylsilanes.