Synthesis of (2S,3S)-[3-(2)H1]-4-methyleneglutamic acid and (2S,3R)-[2,3-(2)H2]-4-methyleneglutamic acid

(2S,3S)-[3-(2)H1]-4-Methyleneglutamic acid 1a and (2S,3R)-[2,3-(2)H2]-4-methyleneglutamic acid 1b have been synthesised for use in biosynthetic and metabolic studies.     

5-羟基色胺受体激动剂(1R,2S)-(-)-2-(2-羟基苯基)-N,N-二丙基环丙胺的不对称合成

利用手性双唑啉与三氟甲磺酸亚铜催化2-甲氧基苯乙烯与重氮乙酸二环己基甲酯的不对称环丙烷化反应合成了手性环丙烷羧酸酯,用氢氧化钠对其进行选择性水解得到全反式环丙烷羧酸,其ee值经GC测定为88%.进一步经过Curtius重排、烷基化等反应及重结晶等步骤合成了光学纯的具有生理活性的环丙胺化合物1a和1b.     

A facile preparation of 2-(2-arylethyl)- and 2-(aminomethyl)indoles

An important process for the acid catalyzed cleavage of the benzoyl group from 3-benzoylindoles in high yield is identified and its application for the facile syntheses of 2-substituted indoles is demonstrated by preparing some 2-(2-arylethyl)- and 2-(aminomethyl)indoles from 1,3-dibenzoyl-2-bromomethylindole (7).     

Synthesis of 2-(2-Naphthyl)quinolines from Z-3-(2-Naphthyl)-3-chloro-2-propenal

By reaction of Z-3-(2-naphthyl)-3-chloro-2-propenal and aromatic amines 1-(2-naphthyl)-3-iminoaryl-1-propenylarylamines were prepared which at heating in the glacial acetic acid afforded the corresponding 2-(2-naphthyl)quinolines.     

2-(2-thiazolylazo)-4-methoxyphenol and 2-(2-thiazolylazo)-5-methoxyphenol as metal-ion indicators

2-(2-Thiazolylazo)-5-methoxyphenol (TAMR) and 2-(2-thiazolylazo)-4-methoxyphenol (TAMH) are shown to be good indicators for the titration of many metal ions with EDTA. TAMH is better and more widely applicable than TAMR. The acid dissociation constants have been determined by spectrophotometry. The effect of pH on the absorbance of the indicators and metal-indicator complexes is reported.     

Sulfonated 1-(2-pyridylazo)-2-naphthols and 2-(2-pyridylazo)-1-naphthols as spectrophotometric reagents: Determination of nickel

Three sulfonated 1-(2-pyridylazo)-2-naphthols and six sulfonated 2-(2-pyridylazo)-1-naphthols were synthesized, and their application to the spectrophotometric determination of metals was studied. The acidity constants of the reagents and the stability constants of the nickel chelates are reported, and the relationship between their properties and the position of the sulfonic acid group is discussed. 1-(2-Pyridylazo)-2-naphthol-6-sulfonic acid (PAN-6S) and 1-(2-pyridylazo)-2-naphthol-7-sulfonic acid (PAN-7S) are sensitive and selective reagents for nickel. The determination of nickel in the presence of cobalt with PAN-6S is described. Extraction of the chelate as the ion-pair with tetraphenylarsonium ions into chloroform is suitable for the determination of 1–10 μg Ni at 570 nm; the molar absorptivity is 56 000 l mol^-1 cm^-1, and interferences are easily avoided.     

Preparation of dimethyl (R)- and (S)-2-(2-aminophenyl)-2-hydroxyethylphosphonate from anthranilic acid

An efficient synthesis of both enantiomers of dimethyl δ-amino-β-hydroxyethylphosphonate 6 has been achieved starting from anthranilic acid, through the resolution of dimethyl (±)-2-(2-N,N-dibenzylaminophenyl)-2-hydroxyethylphosphonate 9 with (S)-O-methylmandelic acid. The absolute configuration of the enantiomers 9 was assigned by the Dale and Mosher approach using the extended Newman projections and molecular mechanics.     

Preparation and root growth-inhibitory activity of N-substituted 2-(2-chloroacetamido)-3-(furan-2-yl)propanamides

A series of N-substituted 2-(2-chloroacetamido)-3-(furan-2-yl)propanamides (16--18) was prepared through the reaction of chloroacetyl chloride with N-substituted 2-amino-3-(furan-2-yl)propanamides (15), which were obtained via condensation of 2-(tert-butoxycarbonylamido)-3-(furan-2-yl)propanoic acid (Boc-furylalanine) (8) with amines (9, 11, 13), followed by hydrolysis of the resultant N-substituted Boc-furylalanine acid amides (10, 12, 14) in the presence of HCl/dioxane. The biological activity of the prepared 16, 17 and 18 as root growth inhibitors was examined by germination assay using rape seed. At the concentration of 5.0 x10 (-5) M, the most active compound, 2-(2-chloroacetamido)-N-(2,6-diethylphenyl)-3-(furan-2-yl)propanamide (16 n), showed potent root growth-inhibitory activity of 76% towards rape seedlings.     

2-(5-Bromo-2-furyl)quinoxaline and 3-(5-bromo-2-furyl)-2-quinoxalone

2-(5-Bromo-2-furyl)quinoxaline and 3-(5-bromo-2-furyl)-2-quinoxalone were obtained by the action of bromine on the corresponding quinoxaline derivatives and also by condensation of o-phenylenediamine with, respectively, (5-bromo-2-furyl)glyoxal or (5-bromo-2-furyl)glyoxylic acid esters.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 404–406, March, 1973.     

Synthesis of Novel New 2-(2-(4-((3,4-Dihydro-4-oxo-3-aryl quinazolin-2-yl)methyl)piperazin-1-yl)acetoyloxy)-2-phenyl Acetic Acid Esters

Stereoselective diazotization of (S)-2-amino-2-phenyl acetic acid (L-phenyl glycine) (4) with NaNO₂ in 6% H₂SO₄ in a mixture of acetone and water gave optically pure (S)-2-hydroxy-2-phenyl acetic acid (L-mandelic acid) (5). Esterification, gave (S)-2-hydroxy-2-phenyl acetic acid esters (6). The latter was treated with chloroacetyl chloride in the presence of triethylamine (TEA) in dichloromethane (DCM) to yield (S)-2-chloroacetyloxy phenyl acetic acid ester (2). In another sequence, the reaction of 2-(chloromethyl)-3-arylquinazolin-4(3H)-one (9) treated with N-Boc piperazine, followed by deprotection of the Boc group, to obtain 3-aryl-2-((piperazin-1-yl)methyl) quinazolin-4(3H)-one (3). Reaction of 2 with 3 in the presence of K₂CO₃ and KI gave the title compound, 2-(2-(4-((3,4-dihydro-4-oxo-3-arylquinazolin-2-yl)methyl)piperazin-1-yl) acetoyloxy)-2-phenyl acetic acid esters (1). The structures of all the new compounds obtained in the present work are supported by spectral and analytical data.     

The synthesis of (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetic acid

The objective was to synthesize (Z)-2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetic acid (the side chain for Ceftaroline fosamil). Oximation and alkylation were used on cyanoacetamide to get 2-cyano-2-hydroxyiminoacetamide, which became 2-ethyoxyiminopropanedinitrile through reaction with phosphorus oxychloride, and then aminolysis to get 2-ethoxyiminopropanedinitrile, which became 2-ethoxyimion-2-(5-amino-1,2,4 thiadiazol-3-yl) acetonitrile by brominating and with KSCN, followed by hydrolysis to get (Z)-2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetic acid.     

2-(2-hydroxyphenyl)-2-adamantanol in Ritter reaction

2-Substituted 4H-1,3-benzoxazines were obtained by the condensation of 2-(2-hydroxyphenyl)-2-adamantanol with aromatic and aliphatic nitriles in trifluoroacetic acid. With acetonitrile the classic product of Ritter reaction, a secondary amide, was isolated.     

Chlorination and decarboxylation of (heptafluoronaphthalen-2-yl)acetic acid. Synthesis of 2-(dichloromethyl)- and 2-(difluoromethyl)heptafluoronaphthalenes

Decarboxylation of (heptafluoronaphthalen-2-yl)acetic acid in DMF in the presence of NaHCO₃ gave 2-methylheptafluoronaphthalene, and treatment with PCl₅ on heating afforded dichloro(heptafluoronaphthalen-2-yl)acetic acid. Decarboxylation of the latter in DMF led to the formation of 2-(dichloromethyl)-heptafluoronaphthalene which was converted to 2-(difluoromethyl)heptafluoronaphthalene by heating with cesium fluoride.     

Study on the Synthesis of (Z)-2-(5-Amino-1,2,4-thiadizol-3-yl)-2-(methoxyimino)acetic Acid

Russian Journal of Organic Chemistry - (Z)-2-(5-Amino-1,2,4-thiadiazole-3-yl)-2-(methoxyimino)acetic acid, an important intermediate prod­uct in the synthesis of Ceftobiprole, was prepared...     

Synthesis and analytical properties of (S)-(+)-2-methoxy-2-(9-phenanthryl)propionic acid

2-Methoxy-2-(9-phenanthryl)propionic acid was synthesized as a novel chiral resolving agent. The absolute configuration of (+)-2-methoxy-2-(9-phenanthryl)propionic acid was determined to be S by using X-ray structural analysis of the (1R,2S,5R)-menthyl ester. In the crystal, the methoxyl and carbonyl groups of the ester are in a syn-periplanar position. The syn-periplanar conformations of (1R,2S,5R)-menthyl esters were also observed by the NMR analyses in CDCl₃. The utility of (S)-(+)-2-methoxy-2-(9-phenanthryl)propionic acid was exemplified by the resolution of (±)-3-octanol.     

Novel synthesis of 2-(trifluoromethyl)- and 2-(perfluoroalkyl)-2-hydroxy-2H-chromenes and their regiospecific reaction with silyl enol ethers

The synthesis of substituted 2-(trifluoromethyl)- and 2-(perfluoroalkyl)-2-hydroxy-2H-chromenes 2a-o was achieved in good yields by intramolecular cyclization of 3-(perfluoroalkyl)-3-phenoxypropenals 1 in the presence of aluminum chloride. Then a Lewis acid mediated nucleophilic reaction with silyl enol ethers 3 proceeded with complete regiospecificity to afford 4-functional 2-(trifluoromethyl)- and 2-(perfluoroalkyl)-4H-chromenes 4a-p with high yields.     

2-(3-ethyl-2,2-dimethylcyclobutyl-methyl)-4(3H)-quinazolinones

Anthranilic acid and its 5-bromo and 4-chloro derivatives react with pinanoic and pinonoic acid chlorides to give the corresponding N-acyl derivatives. The pinanoyl derivatives give the corresponding 2-(3-ethyl-2,2-dimethyl-cyclobutylmethyl)-4-(3H)-quinazolinones when refluxed in formamide. Pinanoylanthranilic acid reacts with dicyclohexylcarbodiimide to give 2-(3-ethyl-2,2-dimethylcyclobutylmethyl)benz-3,1-oxazin-4(H)-one and subsequently with hydrazine hydrate to give 3-amino-2-(3-ethyl-2,2-dimethylcyclobutylmethyl)-4(3H)-quinazolinone. Refluxing of the pinanoyl- and pinonoylanthranilic acids with acetic anhydride gives acetylanthranilic acid, and pinonoylanthranilic acid gives 4(3H)-quinazolinone with formamide.Riga Technical University, Riga LV-1658, Latvia; e-mail: marina@osi.lanet.lv. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 811–817, June, 1999.     

A Practical Synthesis of (S)-(+)-2-(6-methoxyl-2-naphthyl) propionic Acid

a-Arylpropionic acids are an important class of non-steroidal anti-inflammatory agents1,2. The therapeutic efficacy of this class of drugs is well demonstrated by the introduction and extensive use of more than a dozen compounds exemplified by ibuprofen, naproxen, ketoprofen and flurbiprofen etc. However, in recent years the use of enantiomerical pure drugs in chemotherapy is becoming almost mandatory for enhancing specificity of drug action and reducing the toxicity. This awareness led to …     

Asymmetric Hydrogenation Synthesis of (S)-(+)-2-(6′-methoxyl-2-naphthyl) propionic Acid by Cinchona Modified Pd(0)-α-FeOOH Catalyst

During the past decades enormous progress was made in asymmetric catalytic synthesis, an well-known example is BINAP1, the chiral hydrogenation synthesis of S-(+)-naproxen catalyzed by BINAP-Ru dicarboxylate complexes provides excellent enantioselectivity (up to 99% ee) and good chemical yield (92%), however the pressures is relatively high (135-150 atm) and the (S)-BINAP-Ru(III) complex is very expensive. This problem may present a practical limitation. In recent years new methodolo…