- Concise Chemoenzymatic Total Synthesis and Identification of Cellular Targets of Cepafungin I
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Amatuni et al. established a concise chemoenzymatic synthesis of cepafungin I. The route enabled access to a chemoproteomic probe, revealing high selectivity for proteasome subunits β5/2. Potent inhibition was associated with the macrocyclic hydroxyl group and lipid tail. Cepafungin I exhibited similar mode of action with the clinical drug bortezomib. The natural product cepafungin I was recently reported to be one of the most potent covalent inhibitors of the 20S proteasome core particle through a series of in vitro activity assays. Here, we report a short chemoenzymatic total synthesis of cepafungin I featuring the use of a regioselective enzymatic oxidation to prepare a key hydroxylated amino acid building block in a scalable fashion. The strategy developed herein enabled access to a chemoproteomic probe, which in turn revealed the exceptional selectivity and potency of cepafungin I toward the β2 and β5 subunits of the proteasome. Further structure-activity relationship studies suggest the key role of the hydroxyl group in the macrocycle and the identity of the lipid tail in modulating the potency of this natural product family. This study lays the groundwork for further medicinal chemistry exploration to fully realize the anticancer potential of cepafungin I.
- Amatuni, Alexander,Shuster, Anton,Adibekian, Alexander,Renata, Hans
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p. 1318 - 18,1326
(2020/09/02)
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- Highly efficient and practical aerobic oxidation of alcohols by inorganic-ligand supported copper catalysis
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The oxidation of alcohols to aldehydes or ketones is a highly relevant conversion for the pharmaceutical and fine-chemical industries, and for biomass conversion, and is commonly performed using stoichiometric amounts of highly hazardous oxidants. The aerobic oxidation of alcohols with transition metal complex catalysts previously required complicated organic ligands and/or nitroxyl radicals as co-catalysts. Herein, we report an efficient and eco-friendly method to promote the aerobic oxidation of alcohols using an inorganic-ligand supported copper catalyst 1, (NH4)4[CuMo6O18(OH)6], with O2 (1 atm) as the sole oxidant. Catalyst 1 is synthesized directly from cheap and commonly available (NH4)6Mo7O24·4H2O and CuSO4, which consists of a pure inorganic framework built from a central CuII core supported by six MoVIO6 inorganic scaffolds. The copper catalyst 1 exhibits excellent selectivity and activity towards a wide range of substrates in the catalytic oxidation of alcohols, and can avoid the use of toxic oxidants, nitroxyl radicals, and potentially air/moisture sensitive and complicated organic ligands that are not commercially available. Owing to its robust inorganic framework, catalyst 1 shows good stability and reusability, and the catalytic oxidation of alcohols with catalyst 1 could be readily scaled up to gram scale with little loss of catalytic activity, demonstrating great potential of the inorganic-ligand supported Cu catalysts in catalytic chemical transformations.
- Wei, Zheyu,Ru, Shi,Zhao, Qixin,Yu, Han,Zhang, Gang,Wei, Yongge
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supporting information
p. 4069 - 4075
(2019/08/07)
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- Characterization of FabG and FabI of the Streptomyces coelicolor dissociated fatty acid synthase
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Streptomyces coelicolor produces fatty acids for both primary metabolism and for biosynthesis of the secondary metabolite undecylprodiginine. The first and last reductive steps during the chain elongation cycle of fatty acid biosynthesis are catalyzed by FabG and FabI. The S. coelicolor genome sequence has one fabI gene (SCO1814) and three likely fabG genes (SCO1815, SCO1345, and SCO1846). We report the expression, purification, and characterization of the corresponding gene products. Kinetic analyses revealed that all three FabGs and FabI are capable of utilizing both straight and branched-chain β-ketoacyl-NAC and enoyl-NAC substrates, respectively. Furthermore, only SCO1345 differentiates between ACPs from both biosynthetic pathways. The data presented provide the first experimental evidence that SCO1815, SCO1346, and SCO1814 have the catalytic capability to process intermediates in both fatty acid and undecylprodiginine biosynthesis.
- Singh, Renu,Reynolds, Kevin A.
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p. 631 - 640
(2015/03/31)
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- Tuning Product Selectivity in Catalytic Hydroformylation Reactions with Carbon Dioxide Expanded Liquids
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An improved hydroformylation process is provided, which comprises reacting an olefin with CO and H2 in the presence of a hydroformylation catalyst in a liquid that has been volumetrically expanded with a compressed gas, such as supercritical carbon dioxide.
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Page/Page column 6; sheet 1
(2008/06/13)
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- Group of anti-cancer compounds with specific structure and their production method
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Compounds containing a specific branched chain end terminal group, which is isopropyl, sec.-butyl, or tert.-butyl; a polar leading group; and long-chain aliphatic, non-cyclic, saturated or unsaturated, hydrocarbon group linking them; and having anti-cancer and immune boosting activity.
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Page/Page column 26
(2010/11/23)
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- Process for producing alcohol
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It is an object of the present invention to obtain a highly pure alcohol by reducing the aldehyde concentration in the product alcohol efficiently and inexpensively. The invention relates to a process for producing an alcohol including hydrogenating an aldehyde using a hydrogenation catalyst and subjecting the resultant product to distillation/purification, wherein the resultant hydrogenation product is subjected to distillation/purification in the absence of the hydrogenation catalyst or in the presence of the hydrogenation catalyst in such an amount that does not cause a dehydrogenation reaction.
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Page/Page column 5
(2008/06/13)
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- A NEW APPROACH TO THE SYNTHESIS OF OPTICALLY ACTIVE DISPARLURES - ATTRACTANTS OF Porthetria dispar
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A fairly simple and original one-stage method of obtaining optically active attractants of Porthetria dispar-(+)-and (-)-2-methyl-Z- and E-7,8-epoxyoctadecanes has been developed.The synthesis is based on the epoxidation of 2-methyloctadec-Z- and -E-7-enes by chiral peroxide complexes of molybdenum of the type of MoO5-L* in an organic solvent at room temperature.Derivatives of tartaric, lactic, β-aminopropionic, and aspartic acids have been used as the chiral ligands (L*).
- Dzhemilev, U. M.,Fekhretdinov, R. N.,Telin, A. G.,Tolstikov, G. A.,Amirkhanov, D. V.,Krivonogov, V. P.
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p. 482 - 487
(2007/10/02)
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- Hydroformylation of olefinic compounds
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Rhodium catalyzed hydroformylation of olefinic compounds is essentially effected in the presence of a secondary phosphine oxide of the general formula (I) in an amount of at least one mole per gram atom of rhodium, which supresses the thermal degradation of the rhodium catalyst in the hydroformylation stage as well as in the distillation of the reaction products: STR1 wherein, in the formula (I), R1 and R2 are the same or different, substituted or unsubstituted hydrocarbon residues containing not more than 20 carbon atoms. The phosphine oxide of the general formula (I) maintains the catalytic activity over a prolonged period of time and prevents essentially metallic rhodium from sticking to the vessel during distillation of the reaction products from the reaction mixture, and consequently makes recycle of the catalyst easier and enables lowering the hydroformylation pressure.
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