Synthesis of furanyl- and triazolyl-containing α-CF3-α-hydroxy acids and their derivatives

Russian Chemical Bulletin - Starting from methyl trifluoropyruvate, α-CF3-substituted α-methoxy-α-(furan-2-yl) acetic acids and their derivatives and also methyl...     

Click-chemistry approach to isoxazole-containing α-CF3-substituted α-aminocarboxylates and α-aminophosphonates

A convenient strategy for the synthesis of isoxazole-containing α-CF(3)-substituted α-aminocarboxylates and α-aminophosphonates have been developed. The method is based on copper-catalyzed 1,3-dipolar cycloaddition of different aromatic nitrile oxides to functionalized acetylenes.     

Synthesis of α-CF3-substituted carbonyl compounds with relative and absolute stereocontrol using electrophilic CF3-transfer reagents

Evans-type chiral lithium imide enolates undergo diastereoselective α-trifluoromethylation with a hypervalent iodine-CF(3) reagent with up to 91% combined isolated yield and 97:3 dr. The resulting isolated diastereopure products can be further transformed into valuable products without racemization.     

Synthesis of α-CN and α-CF3 N-heterocycles through tandem nucleophilic additions

Using a readily available secondary aminoalkyne as starting material, a powerful strategy was discovered to prepare precursors of biologically important unnatural cyclic aminoacids and fluorinated N-heterocycles with important ring sizes (e.g., 5-7) in a one-pot reaction using two nucleophilic additions in a tandem fashion.     

Fluoro-Hydroxylation of gem-Difluoroalkenes:Synthesis of 18O-labeled α-CF3 Alcohols

in this paper,a fluoro-hydroxylation of gem-difluoroalkenes is demonstrated.This protocol uses sequential electrophilic fluorination with Selectfluor and nucleophilic hydroxylation with H218o,which can be used to prepare 18Oo-labeled α-CF3 alcohols from gem-difluorostyrenes.The reaction is typically carried out at room temperature within 4h in good to excellent yields.Other nucleophiles (besides H218o),such as alcohols,carboxylic acid, acetonitrile and N,N-dimethylformamide,are also suitable for this difunctionalization of gem-difluoroalkenes.     

Synthesis of α-substituted iminodiacetate ligands: α-hexadienyl derivatives for the selection of lipoxygenase mimics

Derivatives of iminodiacetic acid (IDA) are important as ligands for metal ions, having numerous applications in separations, sensing, catalysis and medicine. This report describes the preparation of two types of IDA derivatives (1, 2) that could be covalently attached to a polymer or protein surface via a variable length spacer chain. The parent compounds 1 (R′=H) were easily prepared via N-alkylation of dimethyl iminodiacetate with esters of 6-bromo-hexanoic acid and subsequent selective ester hydrolysis. Metal complexes of IDA derivatives having an α-dienyl side chain are required for the selection of histidine-rich proteins with potential lipoxygenase activity. The α-hexadienyl side chain of IDA derivative 2 was selectively introduced in the reaction of (2,4-hexadienyl acetate)Fe(CO)₃ with a glycine-derived TMS-enol ester. Subsequent demetallation, followed by N-carboxymethylation, N-deacylation, N-alkylation with a trichloroethyl 6-halohexanoate, and TCE-ester cleavage provided the desired α-hexadienyl IDA derivative 2. Amide formation with IDA acid 1b demonstrates the feasibility of conjugating the IDA ligands to polymers and proteins while Ni(II)-complexation with the derived IDA triacid 1e shows the complexing ability of the tethered IDA ligand.     

Polarographic behaviour of α- and γ-substituted acetoacetanilide derivatives in alcoholic aqueous media

A polarographic study on a series of newly synthesized compounds, namely N-(3-pyridyl)-2,3-dioxobutanamide-2-arylhydrazones (1 a–f) in a wide range ofpH is reported and discussed. CPE indicated that these compounds are reduced in the hydrazono form. A scheme is proposed and confirmed through isolation and identification of 2,5-dimethyl-3,6-di[N-(3-pyridyl)amide]-1,4-dihydro-pyrazine as an electrolysis product.

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Das polarographische Verhalten von - und -substituierten Acetoacetanilid-Derivaten in alkoholisch-wäßrigem Medium

Zusammenfassung Es wird über eine polarographische Untersuchung einer Reihe von neu synthetisierten Verbindungen, die N-(3-pyridyl)-acetoacetamid--arylhydrazone1 a–fbd, in einem weitenpH-Bereich berichtet. Kontrollierte Potential-Elektrolyse (CPE) zeigte, daß diese Verbindungen in ihrer Hydrazonoform reduziert werden. Es wird ein Reaktionsschema vorgeschlagen und auch mit der Isolierung und Identifizierung von 2,5-Dimethyl-3,6-di[N-(3-pyridyl)amid]-1,4-dihydropyrazin als Elektrolyseprodukt belegt.

     

Thermal ene reactions of methyl 3,3,3-trifluoro-2-R-sulfonyliminopropionates. Synthesis of γ,δ-unsaturated derivatives ofα-amino α-trifluoromethylcarboxylic acids

Thermal ene reactions of methyl 3,3,3-trifluoro-2-methanesulfonyliminopropionate and methyl 2-benzenesulfonylimino-3,3,3-trifluoropropionate with terminal alkenes afford derivatives of ,-unsaturated -amino -trifluoromethylcarboxylic acids in one step.     

Synthesis and properties of monoimines of α-diketones, derivatives of 3-imidazoline nitroxides

The reaction of 4-(2R-1-chloro-2-oxoethylidene)-substituted imidazolidine-1-oxyl with sodium azide gives monoimines of -diketones, derivatives of 3-imidazoline nitroxides. Reactions of these products with nitrogen binucleophiles were used to prepare various heterocyclic compounds containing an imidazoline nitroxide moiety.     

Synthesis of γ-benzyltert-butoxycarbonyl-L-alanyl-D-glutamate and its derivatives

A convenient method of obtaining Boc-L-Ala-D-iGln-OBzl and its amide analogs by condensing the N-hydroxysuccinimidyl ester of Boc-L-Ala with the -benzyl ester ofD-Glu in the presence of NaHCO₃, followed by amidation of the resulting Boc-L-Ala-D-Glu--OBzl, is proposed. The use of l-adamantylamine and octadecylamine as amino components has enabled the corresponding -adamantylamide and octadecylamide of the dipeptide to be obtained.Simferopol' State University, 4 Yaltinskaya ul., Simferopol', Crimea, Ukraine 333036. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 101–103, January–February, 1998.     

Intramolecular cyclization of acetylene-containing α-amino carboxylates and α-amino phosphonates: synthesis of α-CF3-substituted dehydroprolines and their P-analogs

CF₃-Containing α-arylpropargyl-α-amino carboxylates and α-arylpropargyl-α-amino phosphonates on treatment with the Brønsted or Lewis acids undergo cyclization involving the free NH₂ group and triple bond to yield the corresponding dehydroprolines and their phosphorus analogs.     

Synthesis of protected α-alkyl lanthionine derivatives

Protected α-alkyl lanthionine derivatives were synthesized in five steps starting from a known phenyloxazoline precursor. This approach involved the synthesis of a family of substituted cyclic sulfamidates and their regioselective opening by nucleophilic attack with a protected cysteine. This efficient multistep strategy affords various α-alkylated lanthionine derivatives in high yields.     

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 of Secondary α-Methylene γ-Lactams

N-trimethylsilyl aldimines, on reaction with the isolated organozinc derivative of ethyl α-(bromomethyl) acrylate, afford secondary α-methylene γ-lactams with quite quantitative yields.     

Synthesis of γ,δ-unsaturated quaternary α-alkylamino acids using umpolung reaction and Claisen rearrangement

A new synthesis of γ,δ-unsaturated quaternary α-amino acid derivatives was developed utilizing N-alkylation and Claisen rearrangement of allyl α-iminocarboxylates.     

Synthesis of (α-substituted α-aminophosphinic and α-aminophosphonic acids

The reaction of ketoximes with hypophosphorous acid resulted in previously unknown -substituted--aminophosphinic acids, which were oxidized into the corresponding -substituted--aminophosphonic acids.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2729–2732, November, 1996.     

Synthesis of α-CF3- and α-CCl3 substituted nitrogen heterocycles by aza Diels-Alder and cyclocondensation reactions

Convenient synthetic approaches for α-CF₃- and α-CCl₃ substituted pyridines, hydrogenated pyridines, azanorbornenes, 4H-1,2,4-thiadiazine- and 2H-1,2,6-thiadiazine-1,1-dioxides were developed on the basis of cycloaddition and cyclocondensation reactions of trihaloethaneimines and imidoyl chlorides.     

Synthesis of novel carboranyl derivatives of α-amino acids

New routes to closo-carboranyl derivatives of L-lysine and L-glutamic acid with free gA-NH2 groups were proposed.     

Novel carbonyl complexes of ruthenium with α-substituted oxime derivatives of terpenes

The reactions of Ru₃(CO)₁₂ with 1R,4S,6S-4-dimethylamino-4,7,7-trimethylbicyclo[4.1.0]heptane-3-one oxime (dimethylaminocaraneoxime) (I), 1R,4S,6S-4-methylamino-4,7,7-trimethylbicyclo[4.1.0]heptane-3-one oxime (methylaminocarane oxime) (II), and 1R,2R,5R-2-benzylthio-2,6,6-trimethylbicyclo[3.1.1]heptane-3-one oxime (benzylthiopinaneoxime) (III) were studied. The binuclear complex Ru₂(CO)₄{μ-η³(O,N,X)-L}₂ was formed as the main product in every reaction, when Ru₃(CO)₁₂ was heated with terpenoid to 80°C. In the above complex, two terpene ligands are coordinated in the form of ‘head-to tail’ bridge by the oxime groups at a binuclear metal fragment Ru-Ru. The heteroatom of the second functional group of every bridging ligand (nitrogen of amino group in I and II, sulfur of the thio group in III) is additionally coordinated to the ruthenium atom to give the chelate five-membered ring. Also the reactions of terpenoids I, II, III with Ru₃(CO)₁₂ were performed at room temperature using Me₃NO. In this case, as in the thermal reactions, the main product was the binuclear complex. However, in the reactions of Ru₃(CO)₁₂ with I and II, the trinuclear clusters were isolated that readily transformed to binuclear complexes in a solution. The complexes synthesized can exist as two diasteromers due to their chiral metal core. However, in all the cases, only one diastereomer was isolated, which indicates stereospecific nature of the above reactions. The compounds obtained were characterized by IR, ¹H-, ¹³C{¹H}-, COSY, and HXCOBI-NMR spectroscopy, the specific optical rotation angles were measured. For the binuclear complexes with ligands I, III and for trinuclear cluster with ligand II, single crystals were obtained and studied by X-ray diffraction.     

Asymmetric synthesis of α,β-substituted γ-amino acids via conjugate addition

The first conjugate addition reaction of organocuprates to N-enoyl oxazolidinone where a N-protected γ-nitrogen atom and an α-methyl group are present into α, β-unsaturated system is described. This reaction gave anti-products in moderate yields and high diastereomeric ratios. The anti-products have two contiguous stereogenic centers, one formed by the conjugate addition reaction and the other by a diastereoselective protonation reaction. The removal of chiral oxazolidinone moiety and N-deprotection of amino group furnished chiral α, β-disubstituted γ-amino acids.