A series of new C2-symmetric amino alcohols with multicoordination groups: promising catalysts for synthesis of both enantiomers in the borane-mediated reduction of prochiral ketones

A series of new C(2)-symmetric amino alcohols with multicoordination groups have been synthesized and successfully applied as catalysts in the borane asymmetric reduction of prochiral ketones in refluxing toluene, providing the corresponding secondary alcohols with up to 90% ee. An unusual temperature-dependent reversal of stereochemistry was also observed.     

An efficient synthesis of C2-symmetric chiral binaphthyl ketone catalysts

An efficient synthesis of C2-symmetric chiral binaphthyl ketones 1a and b, effective catalysts for asymmetric epoxidation, is reported. The key features of this synthesis are Co(salen)-catalyzed macrolactonization of racemic 1,1'-binaphthyl-2,2'-dicarboxylic acid monoglycidyl esters 3a and b and lipase-catalyzed enantioselective acylation of resulting 11-membered cyclic binaphthyl alcohols 4a and b.     

Conversion of diphosphatidylglycerol to bis(monoacylglyceryl)phosphate by lysosomes

Diphosphatidyl[1',2',3'-14C]glycerol (cardiolipin) is converted to bis(monoacylglyceryl)phosphate when incubated in vitro with rat lysosomes at pH 4.4. The stereochemical configuration of the product is unknown. This reaction probably takes place via lysophosphatidylglycerol, one of the major products of diphosphatidylglycerol hydrolysis by lysosomes. Phosphatidyl[1',2',3'-14C]glycerol was introduced into mitochondrial membranes by incubating mitochondria with [U-14C]sn-glycerol-3-phosphate and cytidine diphosphate diacylglycerol. Membrane-bound phosphatidyl[1',2',3'-14C]glycerol is also converted to bis(monoacylglycerol)phosphate when incubated with lysosomes in a reaction that is dependent on the concentration of lysosomal protein and on incubation time. These results support our previous proposal (Poorthuis, B. J. H. M., and K. Y. Hostetler, 1976. J. Biol. Chem. 251: 4596-4602) that bis(monoacylglyceryl)phosphate formation may require the interaction of lysosomes with other membranes that contain the substrates for the reaction. The stereochemistry of bis(monoacylglyceryl)phosphate biosynthesis is discussed.     

Ethylene oligomerization using nickel dithiolene complexes Ni(S2C2R2)2 (R=Ph, CF3) and the crystal structure of Ni[S2C2(CF3)2]2

Nickel bis(dithiolene) complexes have been known for over four decades, yet little is known regarding the chemistry of this important subclass of inorganic coordination complexes in olefin oligomerization or polymerization. We report here that Ni(S(2)C(2)R(2))(2) (R=Ph, CF(3)) are converted to active catalysts for ethylene oligomerization when activated with methylaluminoxane (MAO). The catalyst activity is comparable to some nickel coordination complexes with N-donor ligands under similar conditions. The products are mainly butenes and hexenes, with small amounts of higher oligomers. The product distribution pattern is consistent with a nickel hydride species being the active center, where fast beta-hydride elimination limits the products to mostly butenes and hexenes. The exact nature of the active center and the reaction mechanism remain to be investigated. In addition, we determined the crystal structure for Ni[S(2)C(2)(CF(3))(2)](2). The molecule crystallizes in the P2(1)/n space group and adopts a planar geometry with expected bond lengths and angles. Comparing this structure with that for the donor-acceptor complex with perylene reveals elongation of both the Ni-S and the S-C bonds in the latter, suggesting reduction of Ni[S(2)C(2)(CF(3))(2)](2) may have occurred in the latter.     

Synthesis and C(2) -symmetric structure of a cyclotetrapeptide composed of anthranilic acid and leucine

A chiral cyclotetrapeptide (1) was synthesized from 2-nitrobenzoic acid and leucine. A single-crystal X-ray of the compound revealed a C(2) -symmetric bowl-shaped structure. The cyclic compound had a unique hydrogen-bonding network composed of three-centered hydrogen bonds and bifurcated hydrogen bonds between NH and CO of anthranilic residue. The NMR spectra and molecular modeling of 1 also suggested the chiral bowl structure.     

Synthesis of 2-amino-6-(4-[11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester as a novel potential PET gene reporter probe for HBV and HSV-tk in cancers

Acyclic nucleoside 2-amino-6-(4-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (ABE, 1) is a new hepatitis B virus (HBV) specific antiviral reagent and shows high anti-HBV activity. Carbon-11 labeled ABE may serve as a novel reporter probe for positron emission tomography (PET) to image HBV and herpes simplex virus thymidine kinase (HSV-tk) in cancers. The radiolabeling precursors 2-amino-6-(4-hydroxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (10) and 2-N-Boc protected analogue 2-N-bis(Boc)amino-6-(4-hydroxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (12), and the reference standard ABE were synthesized from bis(trifluoroethyl) (2-iodoethoxy)methylphosphonate (5), guanine (6), and 2-amino-6-chloropurine (8). The target radiotracer 2-amino-6-(4-[11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester ([11C]ABE, [11C]1) was prepared by O-[11C]methylation of the unprotected HO-precursor 10, or 2-N-Boc protected HO-precursor 12 with [11C]methyl triflate followed by a quick deprotection reaction, and isolated by solid-phase extraction (SPE) purification in 40-55% radiochemical yields.     

Synthesis of a C3-symmetric (1-->6)-N-acetyl-beta-D-glucosamine octadecasaccharide using click chemistry

A C3-symmetric (1-->6)-N-acetyl-beta-D-glucosamine octadecasaccharide was convergently synthesized on the basis of a copper(I)-catalyzed 1,3-dipolar cycloaddition reaction of azide and alkyne. The target octadecasaccharide showed good antitumor activity against H22 in the preliminary mice tests.     

New bis(macrocyclic) dinickel(II) complexes obtained by oxidation of bis(5,7-dimethyl-1,4,8,11-tetraazacyclotetradeca-4,7-dien-6-yl)dinickel(II) perchlorate

New bis(macrocyclic) dinickel(II) complexes with bis(Me₂[14]-4,7-dien-6-ylidene), 2a and 2b, were synthesized by oxidation of a dinickel(II) complex with an unsaturated bis(macrocyclic) ligand containing four CN bonds, bis(Me₂[14]-4,7-dien-6-yl) (1). Complex 2a was found to undergo intramolecular cyclization between the methyl group of one macrocycle and the carbon atom of the CN group of the other macrocycle to produce a bis(macrocyclic) dinickel(II) complex bridged by a fivemembered ring (3). The structures of 2b and 3 were determined by X-ray crystallography. The nonsymmetrical bis(macrocyclic) structure of the dinickel(II) complex 3 was reflected in its cyclic voltammogram and ¹H and ¹³C NMR spectra. The catalytic capabilities of these bis(macrocyclic) nickel(II) complexes in the reductive debromination of 1-bromo-4-tert-butylbenzene were also investigated.     

Effect of silica type and grafting method on the reactivity of tetraneopentylchromium(IV) towards and on silica

The grafting of tetraneopentylchromium(IV) onto the surface hydroxyls of silica has been investigated by varying both the method of deposition and the nature of the silica support. Reaction of the volatile organometallic with the silica surface in vacuo is compared with reaction in solution. A faster reaction but a lower ultimate Cr loading was obtained using the solution deposition technique. The reactions of the organometallic compound with Aerosil 200, a fumed silica often used to model catalyst supports, and Sylopol 952, a silica gel used as a carrier for chromium-based ethylene polymerization catalysts, are compared. After thermal pretreatment at 200 °C, grafting on both supports yields bis(neopentyl)chromium(IV) fragments regardless of the grafting method used, suggesting that a paired arrangement of the surface hydroxyl groups exists on both types of silicas. The higher Cr loading achieved on the silica gel is attributed to its higher surface area. Thermally-induced neopentane elimination from the grafted bis(neopentyl)chromium(IV) fragments occurs at the same rate and with the same stoichiometry for both Aerosil- and Sylopol-supported materials. Consequently, interactions of the grafted organometallic fragments with nearby siloxanes appear to be unimportant in the early stages of the transformation of bis(alkyl)chromium(IV) to the alkylidene.     

Synthesis of a new C(2)-symmetric chiral catalyst and its application in the catalytic asymmetric borane reduction of prochiral ketones

A new C(2)-symmetric chiral catalyst 3,5-bis[(2S)-(hydroxy-diphenylmethyl)- pyrrolidin-1-ylmethyl]-1,3,4-oxadiazole was successfully synthesized by the reaction of 2,5-dichloromethyl-1,3,4-oxadiazole with (S)-alpha,alpha-diphenyl-2-pyrrolidinemethanol, and applied to the catalytic asymmetric reduction of prochiral ketones with borane. When the catalyst loading was 1 mol %, enantiomeric excesses of up to 86.8% and 94.5% were observed in reduction of aromatic and alpha-halo ketones, respectively.     

A facile synthesis of C(2)-symmetric 17 beta-estradiol dimers

A rapid and efficient synthesis of a series of C(2)-symmetric 17 beta-estradiol dimers is described. The new molecules are linked at position 17 alpha of the steroid nucleus with either an alkyl chain or a polyethylene glycol chain. They are made from estrone in five chemical steps with an overall yield exceeding 30%. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent (ER(+) and ER(-)) human breast tumor cell lines: MCF-7 and MDA-MB-231. Some of the dimers present selective cytotoxic activity against the ER(+) cell line.     

Synthesis, characterization and ethylene polymerization activity of titanium aminopyridinato complexes

Three titanium complexes derived from 2-(2,6-difluoroanilino)pyridine and 2-(2-chloroanilino)pyridine were synthesized and characterized by X-ray diffraction or spectroscopic methods. All titanium complexes have been used to catalyze the polymerization of ethylene in the presence of MAO as cocatalyst. The mono(2,6-difluorophenylaminopyridinato) titanium catalyst was found to be more active in ethylene polymerization than the bis(2,6-difluorophenylaminopyridinato) and bis(2-chlorophenylaminopyridinato) titanium catalysts. ortho-Halogens disturbed the β-elimination transition state of ethylene polymerization and formed higher molar mass polyethylene than their unhalogenated congener. Due to fluxionality, the bis(2-chlorophenylaminopyridinato) titanium catalyst formed broader molar mass distribution than the bis(2,6-difluorophenylaminopyridinato) titanium catalysts.     

New synthesis of (S)-dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethenedioxy-biphenyl-2,2'-dicarboxylate by configuration transform

(R/S)-4,4'-Dimethoxy-5,6,5',6'-dimethenedioxy-2,2'-di-(4(S)-methyl-oxazoline-1)-biphenyl has been synthesized from dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethenedioxy-biphenyl-2,2'-dicarboxylate, and then the diastereoisomer mixture was almost fully converted to a single diastereoisomer with S-configuration ((S)-3) through the key configuration transform promoted by CuI, which was confirmed by CD, HPLC and (13)C NMR. The C(2)-symmetric biphenyl, (S)-dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethenedioxy-biphenyl-2,2'-dicarboxylate was prepared easily via the hydrolysis and ester exchange of (S)-3.     

Axially dissymmetric (R)-(+)-5,5',6,6',7,7',8,8' octahydro-[1,1']binaphthyldiimine chiral salen type-ligands for copper-catalyzed asymmetric aziridination

Axially dissymmetric chiral diimine ligand 2 was prepared from the reaction of (R)-(+)-5,5',6,6',7,7',8,8'-octahydro-[1,1']binaphthyl-2,2'-diamine 1 with 2,6-dichlorobenzaldehyde. The catalytic asymmetric aziridination of alkenes was examined using this novel chiral ligand. Excellent enantioselective aziridination of cinnamates was achieved using C(2)-symmetric chiral ligand 2.     

Bis(L-cysteinato)gold(I): chemical characterization and identification in renal cortical cytoplasm.

L-Cysteinatogold(I) was prepared by the reaction of L-cysteine with KAuBr4 in acidic media and its solubility determined from pH 4 to 10. The solubility at pH 7.4 and 37 degrees C is 1 microM. In the presence of excess cysteine, the solubility increases because of formation of bis(L-cysteinato)gold(I). The equilibrium-constant for formation of the bis complex is 2.1 +/- 0.4 X 10(-3), which at pH 7.4 CORRESPONDs to an apparant formation constant of 4.4 X10(4). The formation of the bis adduct was confirmed by chromatographic separation of the products of the reaction between [35S]-L-cysteine and Na2AuTM. This complex elutes with Kav = 1.15 which allows it to be distinguished from other gold thiolates that might form in vivo. The bis(cysteinato)gold(I) complex is shown to be present in kidney cytosol isolated from rats given Na2AuTM in vivo. When additional cysteine is added to the cytosol in vitro, the peak at 1.15 is increased, but if glutathione is added, the low molecular weight gold elutes at Kav = 1.00, which is taken as evidence for the existence of bis(cysteinato)gold(I) in the cytosol preparation. The amount of gold present as bis(cysteinato)gold(I) after 4 different dose schedules has been measured and found to increase with the total cytosol gold concentration. L-Cysteinatogold(I) does not dissolve in the presence of bovine serum albumin to form an adduct.     

A polarimetric study of the reaction of bis(L-serinato)copper(II) with formaldehyde

Polarimetric data have shown that the base-catalyzed reaction of bis(L-serinato)copper(II) with excess formaldehyde proceeds via the initial dissociation of the proton on the nitrogen atom of the amino acid chelate. A bis(oxazolidine)copper(II) complex appears as an intermediate but this species is not detected polarimetrically at 50°C and above.     

Versatile precursor to ruthenium-bis(phosphine) hydrogenation catalysts

The known complex trans-RuCl2(NBD)Py2 (1, NBD is norbornadiene, Py is pyridine) reacts with either (R)-BINAP ((R)-2, 2'-bis(diphenylphosphino)-1,1'-binaphthyl), (S;S)-Chiraphos ((2S;3S-(-)-2,3-bis(diphenylphosphino)butane), (S;S)-Skewphos ((2S;4S)-(-)-2,4-bis(diphenylphosphino)pentane), (R)-(S)-Josiphos ((R)-(-)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyl-dicyclohexylpho sphine), (R;R)-Norphos ((2R;3R)-(-)-2, 3-bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene), or (R;R)-Me-DUPHOS ((-)-1,2-bis((2R;5R)-2, 5-dimethylphospholano)benzene) to generate in high yields the crystalline complexes trans-RuCl2(P-P*)Py2 (P-P* is the corresponding chiral bis(phosphine)). The complexes trans-RuCl2(P-P*)Py2 are active enantioselective hydrogenation catalysts for ketoesters and noncarboxylic olefins in the presence of small amounts of HBF4 (aq.). They are active for hydrogenation of carboxylic substrates in the presence of Et3N. Reaction of trans-RuCl2(P-P*)Py2 with (rac)-1,2-diphenylethylene-diamine (N-N*, either enantiomer) forms in good yields the corresponding compounds trans-RuCl2(P-P*)(N-N*). Representative hydrogenations with these catalysts are presented.     

First optically active selenurane oxide: resolution of C(2)-symmetric 3,3,3',3'-tetramethyl-1,1'-spirobi [3h,2,1]-benzoxaselenole oxide

The enantiomers of the first optically active selenurane oxide ever reported, C(2)-symmetric 3,3,3',3'-tetramethyl-1,1'-spirobi[3h,2,1]-benzoxaselenole oxide, were isolated via enantioselective liquid chromatography of the racemate or by spontaneous resolution that occurs during the slow evaporation of its acetonitrile solution or the slow crystallization from the same solvent.     

Hydroformylation of alkenes catalyzed by new dinuclear aryloxide- and carboxylate-bridged rhodium complexes

The new dinuclear aryloxide- and carboxylate-bridged rhodium complexes bis[μ-(2-methylphenolato)]bis[(η²:η²-cycloocta-1,5-diene)rhodium], di(μ-docosanoato)bis[(η²:η²-norborna-2,5-diene)rhodium] and bis[(μ-(adamant-1-yl)carboxylato]bis[(η²:η²-norborna-2,5-diene)rhodium] have been prepared. The complexes were tested as catalysts in the hydroformylation of styrene with a total pressure of CO/H₂ (1:1) of 1000 psi, at 25 and 60 °C, and displayed a regioselectivity towards the branched aldehyde of up to 97%. The same complexes as catalysts in the hydroformylation of 1-octene displayed a regioselectivity for the linear aldehyde of up to 55%.     

A mild and environmentally friendly scandium(III) trifluoromethanesulfonate-catalyzed synthesis of bis(3'-indolyl)alkanes and bis(3'-indolyl)-1-deoxyalditols

Bis(3'-indolyl)alkanes and bis(3'-indolyl) derivatives containing a 1-deoxyalditol moiety were synthesized in the presence of 5 mol% of scandium(III) trifluoromethanesulfonate [Sc(OTf)3] in CH3CN or EtOH-H2O mixture as a solvent from room temperature to 70 degrees C in good yields (78-97%).