- Total synthesis of hibispeptin A via Pd-catalyzed C(sp3)-H arylation with sterically hindered aryl iodides
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To access the key Ile-Hpa pseudodipeptide motif in hibispeptins, a series of bidentate carboxamide-based auxiliary groups have been explored to facilitate the palladium-catalyzed arylation of unactivated γ-C(sp3)-H bonds of Ile precursor with a
- He, Gang,Zhang, Shu-Yu,Nack, William A.,Pearson, Ryan,Rabb-Lynch, Javon,Chen, Gong
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Read Online
- Microbiological transformations. Part 48: Enantioselective biohydrolysis of 2-, 3- and 4-pyridyloxirane at high substrate concentration using the Agrobacterium radiobacter AD1 epoxide hydrolase and its Tyr215Phe mutant
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The epoxide hydrolase (EH) from Agrobacterium radiobacter AD1 wild type (ArWT) and its Tyr215Phe mutant were compared for the biocatalyzed hydrolytic kinetic resolution (BHKR) of 2-, 3- and 4-pyridyloxirane. The regioselectivity of the oxirane ring opening as well as the substrate concentration limit and the inhibitory effect of the diol were determined. A gram scale preparation of enantiopure 2-pyridyloxirane (ee>98%) at a concentration as high as 127 mM (15.5 g/L) could be achieved with each of these two enzymes.
- Genzel,Archelas,Lutje Spelberg,Janssen,Furstoss
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Read Online
- Asymmetric azidohydroxylation of styrene derivatives mediated by a biomimetic styrene monooxygenase enzymatic cascade
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Enantioenriched azido alcohols are precursors for valuable chiral aziridines and 1,2-amino alcohols, however their chiral substituted analogues are difficult to access. We established a cascade for the asymmetric azidohydroxylation of styrene derivatives leading to chiral substituted 1,2-azido alcohols via enzymatic asymmetric epoxidation, followed by regioselective azidolysis, affording the azido alcohols with up to two contiguous stereogenic centers. A newly isolated two-component flavoprotein styrene monooxygenase StyA proved to be highly selective for epoxidation with a nicotinamide coenzyme biomimetic as a practical reductant. Coupled with azide as a nucleophile for regioselective ring opening, this chemo-enzymatic cascade produced highly enantioenriched aromatic α-azido alcohols with up to >99% conversion. A bi-enzymatic counterpart with halohydrin dehalogenase-catalyzed azidolysis afforded the alternative β-azido alcohol isomers with up to 94% diastereomeric excess. We anticipate our biocatalytic cascade to be a starting point for more practical production of these chiral compounds with two-component flavoprotein monooxygenases.
- Franssen, Maurice C. R.,Hollmann, Frank,Martínez-Montero, Lía,Paul, Caroline E.,Süss, Philipp,Schallmey, Anett,Tischler, Dirk
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p. 5077 - 5085
(2021/08/16)
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- Organomagnesium Based Flash Chemistry: Continuous Flow Generation and Utilization of Halomethylmagnesium Intermediates
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The generation of highly unstable chloromethylmagnesium chloride in a continuous flow reactor and its reaction with aldehydes and ketones is reported. With this strategy, chlorohydrins and epoxides were synthesized within a total residence time of only 2.6 s. The outcome of the reaction can be tuned by simply using either a basic or an acidic quench. Very good to excellent isolated yields, up to 97%, have been obtained for most cases (30 examples).
- Von Keutz, Timo,Cantillo, David,Kappe, C. Oliver
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supporting information
p. 7537 - 7541
(2020/10/12)
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- Manganese(II)/Picolinic Acid Catalyst System for Epoxidation of Olefins
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An in situ generated catalyst system based on Mn(CF3SO3)2, picolinic acid, and peracetic acid converts an extensive scope of olefins to their epoxides at 0 °C in 5 min, with remarkable oxidant efficiency and no evidence of radical behavior. Competition experiments indicate an electrophilic active oxidant, proposed to be a high-valent Mn = O species. Ligand exploration suggests a general ligand sphere motif contributes to effective oxidation. The method is underscored by its simplicity and use of inexpensive reagents to quickly access high value-added products.
- Moretti, Ross A.,Du Bois,Stack, T. Daniel P.
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supporting information
p. 2528 - 2531
(2016/07/06)
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- Azidolysis of epoxides catalysed by the halohydrin dehalogenase from Arthrobacter sp. AD2 and a mutant with enhanced enantioselectivity: an (S)-selective HHDH
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Halohydrin dehalogenase from Arthrobacter sp. AD2 catalysed azidolysis of epoxides with high regioselectivity and low to moderate (S)-enantioselectivity (E?=?1–16). Mutation of the asparagine 178 to alanine (N178A) showed increased enantioselectivity towards styrene oxide derivatives and glycidyl ethers. Conversion of aromatic epoxides was catalysed by HheA-N178A with complete enantioselectivity, however the regioselectivity was reduced. As a result of the enzyme-catalysed reaction, enantiomerically pure (S)-β-azido alcohols and (R)-α-azido alcohols (ee???99%) were obtained.
- Mikleu?evi?, Ana,Primo?i?, Ines,Hrenar, Tomica,Salopek-Sondi, Branka,Tang, Lixia,Elenkov, Maja Majeri?
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p. 930 - 935
(2016/09/13)
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- Efficient biocatalysis for the production of enantiopure (S)-epoxides using a styrene monooxygenase (SMO) and Leifsonia alcohol dehydrogenase (LSADH) system
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Herein we report the production of enantiopure epoxides through biocatalysis using recombinant Escherichia coli cells expressing Rhodococcus sp. ST-10 styrene monooxygenase (SMO) and Leifsonia sp. S749 alcohol dehydrogenase (LSADH) genes are described. Rhodococcus sp. ST-10 SMO catalyzed the epoxidation of various alkenes, including styrene derivatives, vinyl pyridines, and linear alkenes, to give (S)-epoxides. NADH was regenerated by the reduction of NAD + by LSADH with 2-propanol. The E. coli biocatalyst was used in an aqueous/organic biphasic reaction system and the reaction conditions were optimized. Under the optimized conditions, 170 mM of (S)-styrene oxide was obtained from styrene in the organic phase with excellent enantiomeric excess (99.8%). This biocatalytic process was used to synthesize various (S)-epoxides.
- Toda, Hiroshi,Imae, Ryouta,Itoh, Nobuya
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p. 1542 - 1549
(2013/02/21)
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- Styrene monooxygenase from Pseudomonas sp. LQ26 catalyzes the asymmetric epoxidation of both conjugated and unconjugated alkenes
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A novel styrene monooxygenase (SMO) was isolated from Pseudomonas sp. LQ26, a styrene degrader from activated sludge. Sequence alignment demonstrated that it was the most distant member of all SMOs originating from the genus of Pseudomonas. The substrate spectrum of this enzyme extended beyond typical SMO substrates to 1-allylbenzene analogues, previously reported as non-substrates for the SMO from Pseudomonas fluorescens ST. The results demonstrate for the first time the asymmetric epoxidation of both conjugated and unconjugated alkenes catalyzed by SMO and suggest that a much broader substrate spectrum is expected for SMOs.
- Lin, Hui,Qiao, Jing,Liu, Yan,Wu, Zhong-Liu
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experimental part
p. 236 - 241
(2011/02/22)
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- The synthesis of two potent β-3 adrenergic receptor agonists
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This contribution describes the initial preparation of two potent β-3 receptor agonists 1 and 2. Subsequent scale up of these two compounds was required for further evaluation and proceeded via a common key amine intermediate 24. Synthesis of this key intermediate by way of a Ritter reaction was a vital step in the sequence. Enantioselective Noyori hydrogenation reactions gave access to the chiral epoxides necessary to make the target compounds. Chemistry was developed for the selective dehalogenation of the 2-chloropyridyl group in the presence of a sensitive isoxazole unit to provide access to 1.
- Bradley, Paul A.,Lecouturier, Yann C.,Noeureuil, Pierre,Patel, Bhairavi,Wheeler, Simon,Carroll, Robert J.,Moore, Robert,Snow, Jonathan
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p. 1326 - 1336
(2011/09/20)
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- DNA-based hydrolytic kinetic resolution of epoxides
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DNA-bound copper(II) complexes serve as catalysts for the hydrolytic kinetic resolution of 2-pyridyloxiranes in water. Selectivity factors of up to 2.7 were achieved, indicating a chirality transfer of DNA to epoxides via a coordinated metal ion.
- Dijk, Ewold W.,Feringa, Ben L.,Roelfes, Gerard
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scheme or table
p. 2374 - 2377
(2009/04/11)
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- Oxidative cleavage of alkenes catalyzed by a water/organic soluble manganese porphyrin complex
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Tetrakis(4-hydroxyphenyl)porphyrin [TPP-(OH)4] was modified with poly(ethylene glycol) chain as four side arms, such that this compound is soluble in both organic and water solutions. Complexation of this porphyrin with manganese metal ions resulted in the formation of MnCl-TPP-(PEO750)4. This complex proved to be an excellent catalyst for the oxidative cleavage of C{double bond, long}C bonds, yielding the corresponding carbonyl compounds with sodium periodate as an oxidant. Mechanistic pathway for this cleavage is discussed.
- Liu, Shiuh-Tzung,Reddy, K. Venugopal,Lai, Rung-Yi
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p. 1821 - 1825
(2007/10/03)
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- CETP INHIBITORS
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Compounds having the structures of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis: In the compounds of Formula I, B or R2 is a phenyl group which has an ortho aryl, heterocyclic, benzoheterocyclic or benzocycloalky substituent, and one other position on the 5-membered ring has an aromatic, heterocyclic, cycloalkyl, benzoheterocyclic or benzocycloalky substituent connected directly to the ring or attached to the ring through a -CH2-.
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Page/Page column 42-43
(2010/10/19)
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- Microbiological transformations. 47. A step toward a green chemistry preparation of enantiopure (S)-2-, -3-, and -4-pyridyloxirane via an epoxide hydrolase catalyzed kinetic resolution
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The biocatalyzed hydrolytic kinetic resolution of 2-, 3-, and 4-pyridyloxirane by the Aspergillus niger epoxide hydrolase (EH) has been explored. This was used to perform a gram scale preparation of these epoxides of (S) absolute configuration using a process performed at a concentration as high as 10 g/L (82 mM). All three epoxides have been obtained in a nearly enantiopure form (ee > 98%). Interestingly, it was shown that this biotransformation could be achieved using plain water instead of buffer solution, an important improvement as far as downstream processing of an eventual industrial process is concerned. Neither of these substrates could be obtained in reasonable enantiomeric purity and yield using the nowadays most efficient metal-based catalysts.
- Genzel,Archelas,Broxterman,Schulze,Furstoss
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p. 538 - 543
(2007/10/03)
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- Microbiological transformations. Part 46: Preparation of enantiopure (S)-2-pyridyloxirane via epoxide hydrolase-catalysed kinetic resolution
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The hydrolytic kinetic resolution (HKR) of 2-pyridyloxirane is described, using the overexpressed epoxide hydrolase from the filamentous fungus Aspergillus niger. This allows the preparation of the (S)-enantiomer of this product in enantiopure form (ee >9
- Genzel, Yvonne,Archelas, Alain,Broxterman,Schulze, Birgit,Furstoss, Roland
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p. 3041 - 3044
(2007/10/03)
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- Bioconversion of substituted styrenes to the corresponding enantiomerically pure epoxides by a recombinant Escherichia coli strain
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Enantiomerically pure epoxides are produced by bioconversion of the corresponding styrenes using a recombinant Escherichia coli strain containing the styrene monooxygenase gene cloned from Pseudomonas fluorescens ST. Different procedures were used to opti
- Bernasconi, Silvana,Orsini, Fulvia,Sello, Guido,Colmegna, Andrea,Galli, Enrica,Bestetti, Giuseppina
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p. 9157 - 9161
(2007/10/03)
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- Studies on cognitive enhancing agents. II. Antiamnestic and antihypoxic activities of 1-aryl-2-(2-aminoethoxy)ethanols
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A series of 2-(2-aminoethoxy)-1-phenylethanols having a variety of N- and phenyl-substitution patterns as well as 5- and 6-membered heteroaryl counterparts of our prototype compound 1 (2-(2-dimethylaminoethoxy)-1- phenylethanol) have been prepared and evaluated for antiamnestic and antihypoxic activities. Compound 3b, the 3-methylphenyl analogue of 1, proved to be significantly more potent than I in reversing electroconvulsive shock- induced amnesia as well as CO2-induced learning-impairment in mice. It exhibited low acute toxicity in mice and afforded a greater brain/serum concentration ratio than 1 after oral administration to rats.
- Ono,Yamafuji,Chaki,Morita,Todo,Maekawa,Kitamura,Tai,Narita
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p. 1488 - 1491
(2007/10/03)
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- Analogues of the dioxolanes dexoxadrol and etoxadrol as potential phencyclidine-like agents. Synthesis and structure-activity relationships
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A series of dioxolane analogues based on dexoxadrol ((4S,6S)-2,2-diphenyl- 4-(2-piperidyl)-1,3-dioxolane) and etoxadrol ((2S,4S,6S)-2-ethyl-2-phenyl-4- (2-piperidyl)-1,3-dioxolane) were prepared and tested for their ability to displace [3H]TCP (1-[1-(2-thienyl)cyclohexyl]piperidine) from PCP (1-(1- phenylcyclohexyl)piperidine) binding sites in rat brain tissue homogenates. Qualitative structure-activity relationships within this series were explored through modifications of the three major structural units of dexoxadrol, the piperidine, 1,3-dioxolane, and aromatic rings of the molecule. N-Alkyl derivatives of dexoxadrol were found to be inactive, as were those analogues where the dioxolane ring was modified. Phenyl-substituted etoxadrol analogues were compared to similarly substituted PCP analogues and distinct differences were found in their structure-activity relationships suggesting that the aromatic rings in these two drug classes interact differently with the PCP binding sites. The replacement of the phenyl ring in etoxadrol by either a 2- or 3-thienyl ring led to compounds with affinity comparable to etoxadrol, and the replacement of the ethyl moiety on etoxadrol's dioxolane ring with propyl (7) or isopropyl (8) led to compounds which were more potent than etoxadrol or PCP. The most potent compound was (2S,4S,6S)-2-ethyl-2-(1- chlorophenyl)-4-(2-piperidyl)-1,3-dioxolane (11), where a chlorine moiety was placed in the ortho position in the aromatic ring of etoxadrol. Its potency was comparable with TCP in vitro.
- Thurkauf,Mattson,Richardson,Mirsadeghi,Ornstein,Harrison Jr.,Rice,Jacobson,Monn
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p. 1323 - 1329
(2007/10/02)
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- Synthesis and β-adrenergic antagonism of 2-(aryloxy)-1-(2-piperidyl)ethanols
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A series of erythro- and threo-2-(aryloxy)-1-(2-piperidyl)ethanol derivatives (3) was synthesized from 2-(2-oxiranyl)pyridine for evaluation as β-antagonists. Most compounds displayed high competitive β-blocking potency, but they lacked significant β
- Mauleon,Pujol,Rosell
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p. 2122 - 2126
(2007/10/02)
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- A NOVEL APPROACH TO FUNCTIONALIZATION OF AZINES. OXIRANYL AND THIIRANYL DERIVATIVES OF PYRIDINE, QUINOLINE AND ISOQUINOLINE
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Convenient methods for synthesis of the oxiranyl and thiiranyl derivatives of pyridine, quinoline and isoquinoline have been elaborated.Oxiranes have been synthesized from corresponding aldehydes with dimethylsulfonium methylide in anhydrous medium.Exchange of the oxygen atom in the oxirane ring on sulfur with potassium thiocyanate gave thiiranylazines.
- Kloc, Krystian,Kubicz, Elzbieta,Mlochowski, Jacek
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p. 2517 - 2522
(2007/10/02)
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