- Complementary and selective oxidation of hydrocarbon derivatives by two cytochrome P450 enzymes of the same family
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The cytochrome P450 enzymes CYP101B1 and CYP101C1, which are from the bacterium Novosphingobium aromaticivorans DSM12444, can hydroxylate norisoprenoids with high activity and selectivity. With the goal of expanding and establishing their substrate range with a view to developing applications, the oxidation of a selection of cyclic alkanes, ketones and alcohols was investigated. Cycloalkanes were oxidised, but both enzymes displayed moderate binding affinity and low levels of productive activity. We improved the binding and activity of these substrates with CYP101B1 by making the active site more hydrophobic by switching a histidine residue to a phenylalanine (H85F). The presence of a ketone moiety in the cycloalkane skeleton significantly improved the oxidation activity with both enzymes. CYP101C1 preferably catalysed the oxidation of cycloalkanones at the C-2 position whereas CYP101B1 oxidised these substrates with higher productivity and at positions remote from the carbonyl group. This demonstrates that the binding orientation of the cyclic ketones in the active site of each enzyme must be different. Linear ketones were also oxidised by both enzymes but with lower activity and selectivity. Cyclic substrates with an ester directing group were more efficiently oxidised by CYP101B1 than CYP101C1. Both enzymes catalysed oxidation of these esters with high regioselectively on the ring system remote from the ester directing group. CYP101C1 selectively oxidised certain terpenoid ester substrates, such as α-terpinyl and citronellyl acetate more effectively than CYP101B1. Overall, we establish that the high selectivity and activity of these enzymes could provide new biocatalytic routes to important fine chemicals.
- Sarkar, Md. Raihan,Bell, Stephen G.
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p. 5983 - 5995
(2020/10/08)
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- Catalytic Reductive Pinacol-Type Rearrangement of Unactivated 1,2-Diols through a Concerted, Stereoinvertive Mechanism
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A catalytic pinacol-type reductive rearrangement reaction of internal 1,2-diols is reported herein. Several scaffolds not usually amenable to pinacol-type reactions, such as aliphatic secondary–secondary diols, undergo the transformation well without the need for prefunctionalization. The reaction uses a simple boron catalyst and two silanes and proceeds through a concerted, stereoinvertive mechanism that enables the preparation of highly enantiomerically enriched products. Computational studies have been used to rationalize the preference for migration over direct deoxygenation.
- Drosos, Nikolaos,Cheng, Gui-Juan,Ozkal, Erhan,Cacherat, Bastien,Thiel, Walter,Morandi, Bill
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supporting information
p. 13377 - 13381
(2017/10/17)
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- Preparation method of alpha-hydroxycyclopentadecanone
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The invention discloses a preparation method of alpha-hydroxycyclopentadecanone.The preparation method of the alpha-hydroxycyclopentadecanone includes the steps of adding an appropriate quantity of dry organic solvents and metallic sodium into a dry reaction unit with a temperature gauge, a stirrer, a reflux condensing tube and a dropping funnel, increasing the temperature until the solvents boil under protection of N2, and quickly stirring to break the metallic sodium into fine particles; heating a reaction system to a specific temperature, dropwise adding pentadecanedioic acid cyclodiester dissolved in the dry organic solvents slowly into a reaction unit, and continuing performing heat reaction for a period of time after dropwise adding is terminated; after reaction is terminated, dropwise adding an appropriate quantity of absolute ethyl alcohol to remove residual metallic sodium; after the metallic sodium is deposed completely, filtering out undissolved substances, washing filtrate to be neutral and subjecting the solvents to spin drying so as to obtain an alpha-hydroxycyclopentadecanone crude product.The pentadecanedioic acid cyclodiester is used for acyloin condensation as a raw material, so that intermolecular side reaction is inhibited effectively.The preparation method of the alpha-hydroxycyclopentadecanone has the advantages of high product yield, high purity and suitability for industrial production.
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Paragraph 0029
(2017/03/28)
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- A practical synthesis of (E)-2-cyclopentadecen-1-one: an important precursor of macrocyclic muscone
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A practical synthesis of (E)-2-cyclopentadecen-1-one (E)-2 which is an important precursor of macrocyclic muscone (1) was investigated. Olefination of 2-mesyloxycyclopentadecanone (7c) with strong acid such as sulfuric acid or trifluoromethanesulfonic acid afforded the desired (E)-2 in high yield with extremely high stereoselectivity, which was treated with methylmagnesium cuprate to furnish the dl-muscone in good yield.
- Hisanaga, Yusuke,Asumi, Yuya,Takahashi, Masaki,Shimizu, Yasuhiro,Mase, Nobuyuki,Yoda, Hidemi,Takabe, Kunihiko
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p. 548 - 551
(2008/04/13)
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- Photo-irradiation of α-halo carbonyl compounds: A novel synthesis of α-hydroxy- and α,α′-dihydroxyketones
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The reaction of α-halo ketones (α-iodocycloalkanones, α-bromocycloalkanones, α-iodo-β-alkoxy esters, and α-iodoacyclicketones) with irradiation under a high-pressure mercury lamp gave the corresponding α-hydroxyketones in good yields. For α-bromoketones, it was found that α-hydroxylation does not occur. However, α-bromoketones were converted into α-hydroxyketones in the presence of KI. In the case of α,α′-diiodo ketones, α,α′-dihydroxyketones, which up to now have scarcely been reported, were obtained. This reaction affords a new, clean and convenient synthetic method for α-hydroxy- and α,α′- dihydroxyketones.
- Chai, Wen,Takeda, Akihiro,Hara, Makoto,Ji, Shun-Jun,Horiuchi, C. Akira
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p. 2453 - 2463
(2007/10/03)
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- A novel synthesis of α-hydroxy- and α,α′- dihydroxyketone from α-iodo and α,α′-diiodo ketone using photoirradiation
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A novel reaction of α-iodo ketone (α-iodocycloalkanone, α-iodo-β-alkoxy ester, and α-iodoacyclicketone) with irradiation under a high-pressure mercury lamp gave the corresponding α-hydroxyketone in good yields. In the case of α,α′- diiodo ketone, α,α′-dihydroxyketone which little has been reported until now was obtained. This reaction affords a new, clean and convenient synthetic method for α-hydroxy- and α,α′- dihydroxyketone.
- Horiuchi, C. Akira,Takeda, Akinori,Chai, Wen,Ohwada, Kishoh,Ji, Shun-Jun,Takahashi, T. Tomoyoshi
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p. 9307 - 9311
(2007/10/03)
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- A facile electrochemical approach for the synthesis of macrocyclic alkanones
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The synthesis of macrocyclic alkanones, viz. cyclotetradecanone 4a, cyclohexadecanone 4b, cyclooctadecanone 4c, cyclopentadecanone 4d and cycloheptadecanone 4e have been carried out by using Kolbe symmetrical/unsymmetrical dimerization followed by cyclization in Na-xylene and subsequent reduction with Zn-HCI in 70-80% yield. The products of anodic cross coupling have been separated by column chromatography over silica gel (60-120 mesh) by eluting with benzene-methanol (95: 5). An effort has been made to optimize the electrochemical step by investigating the effect of different parameters, viz. degree of partial neutralization, current density and electrode material. The products have been characterised by elemental analyses and IR and 1H NMR spectral data.
- Singh, Arpita,Singhal, Nishi,Agrawal, Hemlata,Yadav, Ashok K.
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p. 423 - 426
(2007/10/03)
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- Process for preparing macrocyclic ketones
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An improvement in a process for preparing a macrocyclic ketone having from 12 to 18 carbon atoms which comprises intramolecular cyclization of a lower alcohol diester of a straight chain alkanedicarboxylic acid having from 12 to 18 carbon atoms by acyloin condensation and reduction of the resulting 2-hydroxycycloalkanone is disclosed. The improvement comprises conducting the acyloin condensation in a water-immiscible organic solvent having a boiling point of not lower than 40°C., subjecting the resulting organic solvent solution containing the 2-hydroxycycloalkanone to reduction, and conducting the reduction in the copresence of said organic solvent and water. The macrocyclic ketone can be prepared at high efficiency.
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- Process for preparing macrocyclic ketones
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An improvement in a process for preparing a macrocyclic ketone having from 12 to 18 carbon atoms which comprises intramolecular cyclization of a lower alcohol diester of a straight chain alkanedicarboxylic acid having from 12 to 18 carbon atoms by acyloin condensation and reduction of the resulting 2-hydroxycycloalkanone is disclosed. The improvement comprises conducting the acyloin condensation in a water-immiscible organic solvent having a boiling point of not lower than 40°C, subjecting the resulting organic solvent solution containing the 2--hydroxycycloalkanone to reduction, and conducting the reduction in the copresence of said organic solvent and water. The macrocyclic ketone can be prepared at high efficiency.
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