Synthesis of α-trifluoromethyl-phenethylamines from α-trifluoromethyl β-aryl enamines and β-chloro-β-(trifluoromethyl)styrenes

A novel synthetic approach towards α-trifluoromethyl-phenethylamines was elaborated by reduction of the electron deficient β-aryl-α-trifluoromethyl enamines and imines with sodium cyanoborohydride in the presence of trifluoroacetic acid. The starting imines were prepared by the reaction of primary amines with β-aryl-α-trifluoromethyl enamines or β-chloro-β-(trifluoromethyl)styrenes.     

Synthesis of β-amino-α-trifluoromethyl alcohols and their applications in organic synthesis

A comprehensive overview on methods applied for syntheses of β-amino-α-trifluoromethyl alcohols, including stereocontrolled variants, is presented. In addition, reported cases of the exploration of β-amino-α-trifluoromethyl alcohols for the preparation of trifluoromethylated peptidomimetics and other biologically active, fluorinated compounds are discussed. Attractive opportunities for their applications as organocatalysts are also presented.     

Synthesis and biological activity of α-alkylacrolein dimers and their derivatives

Dimers of methacrolein and α-ethylacrolein have been obtained and undergo a Cannizzaro reaction to the corresponding pyran alcohols and sodium salts of pyran acids. Their bacteriostatic, bactericidal, and fungicidal properties have been studied. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1639–1644, November, 2008.     

Synthesis and anti-tumor activity of β-C-glycoside analogs of the immunostimulant KRN7000

A ring-closing metathesis approach was employed for the synthesis of a β-C-glycoside analog of the immunostimulant KRN7000. The protected C-glycosyl amino acid derivative 18 was converted to amino-olefin 20, and osmylation served to install the diol unit as a mixture of separable syn and anti isomers. Deprotection to the hydroxy-amine 21 was followed by N-acylation and debenzylation to deliver the target compound 5.     

Facile synthetic pathway to β-hydroxy-β-trifluoromethyl imines and their derivatives

Synthetic approach based on mediated addition of different trifluoromethylated building blocks to selected acyclic imines giving access to a variety of β-hydroxy-β-trifluoromethyl imines are elaborated. A reaction between fluorinated adducts and imines proceed easily giving the condensation products in good to excellent yields. β-Hydroxy-β-trifluoromethyl imines possessing trifluoromethyl group and exhibiting strong intramolecular hydrogen bonding are great precursors to different β-hydroxy-β-trifluoromethyl ketones and alcohols.     

Fluorine containing amino acids and their derivatives. 7. Synthesis and antitumor activity of α- and γ-substituted methotrexate analogs

Three types of reactions of α-substituted malonates, difluoromethylation, alkylation with n,n,n-trifluoroalkyl sulfonates, and Michael addition to 2-substituted-acrylates, conveniently afforded a number of fluorine containing α amino acids such as β-fluorinated-alanines, 2-amino-n,n,n-trifluoroalkanoic acids, and fluorinated glutamic acids as well as other γ-heteroatom substituted glutamic acids. Here, an efficient enzymatic optical resolution using hog kidney acylase was conducted to obtain both optical isomers of 2-amino-n,n,n-trifluoroalkanoic acids. In addition, a novel sulfoxide rearrangement was observed in a base-catalyzed reaction of diethyl α-difluoromethyl-α-sulfoxymalonates. Finally, α- and γ-substituted glutamic acids obtained were used for chemical modification of the antitumor agent methotrexate to reveal remarkable structure-activity relationships. In particular, the significant effects of fluorine substitution on the in vivo antitumor activity were observed.     

Synthesis and biological investigation of the β-thiolactone and β-lactam analogs of tetrahydrolipstatin

The synthesis of β-thiolactone and β-lactam analogs of tetrahydrolipstatin is described from a common late-stage β-lactone derivative. These analogs, and a cis-disubstituted β-lactone analog of tetrahydrolipstatin, were screened for activity against porcine pancreatic lipase and for inhibition of cell growth of a panel of four human cancer lines.     

Synthesis and antibacterial activity of 4“-O-carbamoyl analogs of clarithromycin

<正>A series of novel 4-O-carbamoyl analogs of clarithromycin were synthesized and evaluated for their in vitro antibacterial activity. All of the desired compounds showed excellent activity against erythromycin-susceptible S.pneumoniae.Particularly,4-fluorobenzyl carbamate 7a demonstrated potent activity against erythromycin-resistant S.pneumoniae encoded by the mef gene,and remarkably improved activity against erythromycin-resistant S.pneumoniae encoded by the erm gene,and the erm and mef genes.     

Synthesis of new β-trifluoromethyl containing GABA and β-fluoromethyl containing N-benzylpyrrolidinones

A whole series of 3-(mono-, di-, trifluoro)methyl-substituted N-benzylpyrrolidinones 5a-c was synthesized by deoxyfluorination of corresponding 3-functionalized N-benzylpyrrolidinones. New β-trifluoromethyl containing GABA 4a was obtained in two alternative ways: by successive hydrolysis and hydrogenolysis of 3-trifluoromethyl N-benzylpyrrolidinone 5a and from trifluoroacetone as starting compound.     

Synthesis of α-N-Ethylamino Acids and their Derivatives

 A new synthesis of α-N-ethylamino acids starting from α-amino acids using hexafluoroacetone as protecting and activating agent is described. The hexafluoroacetone-protected N-ethylamino acid derivatives obtained are activated lactons. Therefore, they can be directly transformed without the need of an additional activation step with various nucleophiles into the corresponding carboxylic acid derivatives.     

Synthesis of α-trifluoromethyl-α-hydroxycarboxylate dervatives and their phosphorus-containing analogs with the use of fluorinated diazo compounds

Approach was developed underlain by the use of fluorinated diazocompounds to the synthesis of derivatives of α-trifluoromethyl-α-hydroxycarboxylic acids and their phosphorus-containing analogs, α-trifluoromethyl-α-hydroxyphosphonic acids. Methyl 2-diazo-3,3,3-trifluoropropionate and diethyl 1-diazo-2,2,2-trifluoroethylphosphonate under the action of catalytic quantities of dirhodium tetraacetate Rh₂(OAc)₄ easily inserted into the O-H bond leading to the formation of the corresponding products in high yields.     

Synthesis and α-amylase inhibitory activity of glucose-deoxynojirimycin conjugates

Inhibitors of α-amylase have attracted attention for their putative effects against diabetes mellitus. Although numerous studies have explored natural small molecule inhibitors, acarbose is currently the only compound with sufficient inhibitory potency and drug-like characteristics to be considered as a potential therapeutic agent. We have synthesized conjugates of the potent glucosidase inhibitor, 1-deoxynojirimycin, and glucose, with the aim of enhancing inhibitory activity against α-amylase. This synthetic conjugate showed increased inhibition of α-amylase compared to 1-deoxynojirimycin alone, suggesting that similar modifications of existing glucosidase inhibitors may yield more potent α-amylase inhibitors.     

Synthesis and structure—activity relationships of cyclopropane-containing analogs of pharmacologically active compounds

The review summarizes information on cyclopropane as an independent pharmacophore group and as a fragment for modification of pharmacological activity level of medicines used in practice. The advantages of a cyclopropane fragment over its bioisosteres are that, on the one hand, this fragment imposes conformational rigidity on the molecules of physiologically active compounds and, on the other hand, the replacement of acyclic terminal and “linker” groups with a cyclopropane fragment increases the metabolic stability of the target structures and extends the scope of their therapeutic action.     

β,β-Difluoro analogs of α-oxo-β-phenylpropionic acid and phenylalanine

A simple three-step procedure converted the readily accessible (2-bromo-1,1-difluoroethyl)arenes (2) into α-aryl-α,α-difluoroacetaldehydes (1). Subsequent hydrocyanation, hydrolysis, oxidation and again hydrolysis afforded β-aryl-β,β-difluoro-α-oxopropionic acids (3). Reductive amination transformed the oxoacids 3 into a separable mixture of α-hydroxyacids 11 and racemic β,β-difluoro-β-phenylalanine derivatives (4). Enantiomerically pure β,β-difluorophenylalanine (l-4a) was obtained when α,α-difluoro-α-phenylacet-aldehyde (1a) was condensed with homochiral 1-phenylethylamine, hydrogen cyanide added to the resulting imine, the diastereomeric mixture thus produced hydrolyzed to the carboxamides (15) which were found to be separable by fractional crystallization or chromatography. The pK_a values of the β-aryl-β,β-difluoroalanines (4) were measured and biological profile of the latter probed. 3-(4-Chlorophenyl)-3,3-difluoro-2-oxopropionic acid (4c) proved to be a potent (K_i 27 μM) and selective inhibitor of arogenate dehydratase, a key enzyme catalyzing the last step of the phenylalanine biosynthesis.     

Synthesis and characterization of organotitanium substituted heteropolytungstosilicates and their biological activity

Tris-, di-(organotitanium) substituted tungstosilicates α、β-[(CpTi)3(SiW9O37)]7- and γ-[(Cp-Ti)2(SiW10O38)]6- were prepared by the reaction of Cp2TiCl2 (Cp = η5-C5H5) with α、β-SiW9O349- (noted α、β-SiW9), γ-SiWO368- (noted γ-SiW10) . The products were characterized by means of elemental analysis, IR, 1H NMR, 183W NMR and polarography. 183W NMR spectra of the complexes support the stoichiometry of the new heteropolyanions and the probable retention of the A-XWg or γ-SiW10 units. And the organotitanium substituted compounds showed promising in vitro antitumor activity in two of human tumor cell lines.     

Synthesis and Stereochemistry of α-Aryl-β-Nitroalkylphosphinate

Abstract

Twenty-three new α -aryl-β -nitroalkylphosphinates 3a - g were synthesized in high yields under very mild conditions. Compounds 3 consist of two pairs of diastereomeric isomers (A) and (B)     

Synthesis and structures of mono(β-diiminato) copper complexes and their catalytic performances for homo- and copolymerizations of methyl acrylate

A series of mono(β-diiminato) copper complexes bearing different coordinating anions and with different fluorine substitution patterns on the β-diiminato ligands were synthesized. All of the complexes were characterized by physicochemical and spectroscopic methods, and in addition, the structures of two of them were confirmed by X-ray diffraction. The crystal structures revealed a four-coordinate mode around the copper center in a slightly distorted square planar geometry, with the β-diimine and the carboxyl groups coordinated to give six- and four-membered chelate rings. The conjugation of C=C and C=N in the β-diiminato ligands and the resonance between C–O and C=O in the carboxyl groups resulted in extensive delocalization of electrons and the formation of conjugated N–C–C–C–N and O–C–O π-bonds, respectively. When activated by modified methylaluminoxane (MMAO), these complexes can effectively catalyze methacrylate (MA) polymerization with activities up to 54.5 kg/mol Cu h, as well as MA/1-hexene copolymerization with the incorporation of MA over 80 %.     

Synthesis of β-Dimethylaminoethyl and α-Hydroxy-β-Dimethylaminoethyl Derivatives from Organolithium Compounds and Tetramethyoxamide

The important biological activity of a variety of aromatic and heterocyclic systems having β-dimethylaminoethyl side chains and their α-hydroxy analogs (c.f. bufotenin, N-methylepinephrine, etc.) has focused the attention of the organic chemist on methods of introducing these functions, and a variety of approaches have been developed. A convenient synthesis has recently been reported³, which utilizes the α-hydroxy-β-dimethylaminoethyl function as an intermediate in the preparation of β-dimethylaminoethyl derivatives, thus providing either or both of these pharmacophoric groups.