- Synthesis of l-threitol-based crown ethers and their application as enantioselective phase transfer catalyst in Michael additions
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A few new l-threitol-based lariat ethers incorporating a monoaza-15-crown-5 unit were synthesized starting from diethyl l-tartrate. These macrocycles were used as phase transfer catalysts in asymmetric Michael addition reactions under mild conditions to afford the adducts in a few cases in good to excellent enantioselectivities. The addition of 2-nitropropane to trans-chalcone, and the reaction of diethyl acetamidomalonate with β-nitrostyrene resulted in the chiral Michael adducts in good enantioselectivities (90% and 95%, respectively). The substituents of chalcone had a significant impact on the yield and enantioselectivity in the reaction of diethyl acetoxymalonate. The highest enantiomeric excess (ee) values (99% ee) were measured in the case of 4-chloro- and 4-methoxychalcone. The phase transfer catalyzed cyclopropanation reaction of chalcone and benzylidene-malononitriles using diethyl bromomalonate as the nucleophile (MIRC reaction) was also developed. The corresponding chiral cyclopropane diesters were obtained in moderate to good (up to 99%) enantioselectivities in the presence of the threitol-based crown ethers.
- Rapi, Zsolt,Nemcsok, Tamás,Pálv?lgyi, ádám,Keglevich, Gy?rgy,Grün, Alajos,Bakó, Péter
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- Hydrogen Bonding-Assisted Enhancement of the Reaction Rate and Selectivity in the Kinetic Resolution of d,l-1,2-Diols with Chiral Nucleophilic Catalysts
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An extremely efficient acylative kinetic resolution of d,l-1,2-diols in the presence of only 0.5 mol% of binaphthyl-based chiral N,N-4-dimethylaminopyridine was developed (selectivity factor of up to 180). Several key experiments revealed that hydrogen bonding between the tert-alcohol unit(s) of the catalyst and the 1,2-diol unit of the substrate is critical for accelerating the rate of monoacylation and achieving high enantioselectivity. This catalytic system can be applied to a wide range of substrates involving racemic acyclic and cyclic 1,2-diols with high selectivity factors. The kinetic resolution of d,l-hydrobenzoin and trans-1,2-cyclohexanediol on a multigram scale (10 g) also proceeded with high selectivity and under moderate reaction conditions: (i) very low catalyst loading (0.1 mol%); (ii) an easily achievable low reaction temperature (0 °C); (iii) high substrate concentration (1.0 M); and (iv) short reaction time (30 min). (Figure presented.).
- Fujii, Kazuki,Mitsudo, Koichi,Mandai, Hiroki,Suga, Seiji
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supporting information
p. 2778 - 2788
(2017/08/23)
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- An optimized synthetic route for the preparation of the versatile chiral building block 1,4-di-O-benzylthreitol
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An improved five-step procedure has been applied to synthesize enantiopure l- and d-1,4-di-O-benzylthreitol out of readily available l- and d-tartaric acid. Through the use of modern reagents and enhanced work-up conditions these useful auxiliaries were o
- Meier, Bettina,Kollroser, Manfred,Presser, Armin
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p. 305 - 309
(2014/03/21)
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- Development of diacyltetrol lipids as activators for the C1 domain of protein kinase C
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The protein kinase C (PKC) family of serine/threonine kinases is an attractive drug target for the treatment of cancer and other diseases. Diacylglycerol (DAG), phorbol esters and others act as ligands for the C1 domain of PKC isoforms. Inspection of the crystal structure of the PKCδ C1b subdomain in complex with phorbol-13-O-acetate shows that one carbonyl group and two hydroxyl groups play pivotal roles in recognition of the C1 domain. To understand the importance of two hydroxyl groups of phorbol esters in PKC binding and to develop effective PKC activators, we synthesized DAG like diacyltetrols (DATs) and studied binding affinities with C1b subdomains of PKCδ and PKC. DATs, with the stereochemistry of natural DAGs at the sn-2 position, were synthesized from (+)-diethyl l-tartrate in four to seven steps as single isomers. The calculated EC50 values for the short and long chain DATs varied in the range of 3-6 μM. Furthermore, the fluorescence anisotropy values of the proteins were increased in the presence of DATs in a similar manner to that of DAGs. Molecular docking of DATs (1b-4b) with PKCδ C1b showed that the DATs form hydrogen bonds with the polar residues and backbone of the protein, at the same binding site, as that of DAG and phorbol esters. Our findings reveal that DATs represent an attractive group of C1 domain ligands that can be used as research tools or further structurally modified for potential drug development.
- Mamidi, Narsimha,Gorai, Sukhamoy,Mukherjee, Rakesh,Manna, Debasis
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experimental part
p. 1275 - 1285
(2012/06/04)
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- Synthesis of chiral and modifiable hexahydroxydiphenoyl compounds
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A reliable method for synthesizing each enantiomer of the hexahydroxydiphenoyl (HHDP) compounds has been developed. The synthesis involved atropselective construction of the aryl - aryl bond of the HHDP compounds. This construction relied on the CuCl2·n-BuNH2-mediated intramolecular coupling of bis(4-O-benzylgallate) on two simple chiral auxiliaries, both of which were derived from l-(+)-tartaric acid. The coupling reaction realized complete or near-perfect atropselectivity. The two auxiliaries induced opposite axial chirality despite their identical origin. The diastereoselectivities of these couplings were probably controlled kinetically. Modifications of the free phenolic hydroxy groups and the carbonyl groups in the resulting HHDP compounds demonstrated the potential derivatization of a wide variety of HHDP analogues.
- Asakura, Noriaki,Fujimoto, Shohei,Michihata, Naoki,Nishii, Kentaro,Imagawa, Hiroshi,Yamada, Hidetoshi
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p. 9711 - 9719
(2012/01/04)
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- FeCl3-catalysed cleavage of 1,2-butanediacetal protected diols
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Catalytic FeCl3 in acetic acid has been employed as a cost-effective, low-toxicity reagent for the removal of butane 1,2-diacetal protecting groups under mild conditions. Georg Thieme Verlag Stuttgart.
- Tzschucke, C. Christoph,Pradidphol, Narathip,Diéguez-Vázquez, Alejandro,Kongkathip, Boonsong,Kongkathip, Ngampong,Ley, Steven V.
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experimental part
p. 1293 - 1296
(2009/04/06)
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- New supramolecular host systems, 11. The stereoisomeric diaminobutanediol and dioxadiazadecalin systems: Synthesis, structure, stereoelectronics, and conformation - Theory vs. experiment
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We present new approaches to the (C2) chiral and meso 1,4-diamino-2,3- butanediol (1) and 2,3-diamino-1,4-butanediol (2) and derivatives. Reactions of these compounds with aldehydes to form the novel 1,5-dioxa-3,7- diazadecalin (DODAD) and 1,5-diaza-3,7-dioxadecalin (DADOD) classes of compounds (7, 9, 11-15) are also reported. These reactions are diastereospecific, i e, erythro (meso) or threo starting compounds lead to trans or cis products, respectively. The structural, conformational, and stereoelectronic aspects of these systems were probed experimentally and computationally and provided excellent insight into their properties and behaviour. Good agreement was observed between X-ray, NMR, and calculated results of the N,N'-dibenzyl derivatives of trans-DODAD (14) and trans-DADOD (15).
- Star, Alexander,Goldberg, Israel,Lemcoff, N. Gabriel,Fuchs, Benzion
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p. 2033 - 2043
(2007/10/03)
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- Comparative Study of Mono- and Di-substituted 14-Crown-4 Derivatives as Lithium Ionophores
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14-Crown-4 derivatives bearing either one or two methoxy, methoxycarbonylmethyl or carbamoylalkyl substituents have been prepared in an attempt to obtain selective ionophores for lithium ions.Complexation with lithium has been fabricated and evaluated using the fixed interference method.The highest selectivity for lithium with respect to sodium is observed for a diamide derivative (630:1).
- Kataky, Ritu,Nicholson, Patrick E. Patrick,Parker, David
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p. 321 - 327
(2007/10/02)
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- OPTICALLY ACTIVE SYNTHONS FOR THE SYNTHESIS OF PROSTANOIDS I. SEPARATION OF THE ENANTIOMERS OF 2-EXO-BROMO-3-ENDO-HYDROXYBICYCLOHEPTAN-6-ONE
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Racemic 2-exo-bromo-3-endo-hydroxybicycloheptan-6-one, which is an intermediate for the synthesis of prostanoids, was separated into the enantiomers in the form of the diastereomeric acetals of (S,S)-(-)-1,4-bis(benzyloxy)-2,3-butanediol (the tartaric acid derivative)
- Kanger, T. P.,Kabat, M.,Vikha, E.,Lopp, M. I.,Lille, Yu. E.
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p. 1481 - 1484
(2007/10/02)
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- Enanthioselective Phase-Transfer Catalysis by Optically Active Crown Ethers
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1,2-Bis(hydroxymethyl)-15-crown-5 (1a), its dibenzyl ether (1b), and a series of esters with substituted benzoic acid (3) were probed as enanthioselective phase-transfer catalysts.Optical yields were observed in epoxidations of unsaturated ketones by hypochlorite and in cyanide additions to such compounds.The maximum ee value was 45percent.Polar side groups of the optically active crown ethers proved to be vital for enanthiomeric excesses.
- Dehmlow, Eckehard V.,Sauerbier, Christiane
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p. 181 - 186
(2007/10/02)
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- HOMOCHIRAL KETALS IN ORGANIC SYNTHESIS. DIASTEREOSELECTIVE CYCLOPROPANATION OF α,β-UNSATURATED KETALS DERIVED FROM 1,4-Di-O-BENZYL-L-THREITOL
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2-Cykloalken-1-one 1,4-di-O-benzyl-L-threitol ketals undergo efficient and diastereoselective cyclopropanation when treated with an excess of the Simmons-Smith reagent.For example, 2-cyclohexen-1-one 1,4-di-O-benzyl-L-threitol ketal gave in 90-98percent yield a 9:1 mixture of diastereomeric cyclopropanes as established by 62.9 MHz 13C NMR spectroscopy and by hydrolysis of the mixture to (1R,6S)-bicycloheptan-2-one.Sixteen other examples are presented which demonstrate the generality and predictability of the process for 2-cycloalken-1-one ketals, as well as an unfortunate lack of diastereoselectivity for α,β-unsaturated 1,4-di-O-benzyl-L-threitol acetals.
- Mash, Eugene A.,Nelson, Keith A.
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p. 679 - 692
(2007/10/02)
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