7533-40-6Relevant articles and documents
Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics
Lee, Jin Woo,Collins, Jennifer E.,Wendt, Karen L.,Chakrabarti, Debopam,Cichewicz, Robert H.
supporting information, p. 503 - 517 (2021/03/01)
Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected to leave vast portions of humanity unprotected against the disease. To address this need, systematic testing of a fungal natural product extract library assembled through the University of Oklahoma Citizen Science Soil Collection Program has generated an initial set of bioactive extracts that exhibit potent antiplasmodial activity (EC50 25 μM, selectivity index > 250). The unique chemodiversity afforded by these fungal isolates serves to unlock new opportunities for translating peptaibols into a bioactive scaffold worthy of further development.
Palladium(0)-Catalyzed Enantioselective Intramolecular Arylation of Enantiotopic Secondary C?H Bonds
Melot, Romain,Zuccarello, Marco,Cavalli, Diana,Niggli, Nadja,Devereux, Michael,Bürgi, Thomas,Baudoin, Olivier
supporting information, p. 7245 - 7250 (2021/02/12)
The enantioselective functionalization of nonactivated enantiotopic secondary C?H bonds is one of the greatest challenges in transition-metal-catalyzed C?H activation proceeding by an inner-sphere mechanism. Such reactions have remained elusive within the realm of Pd0 catalysis. Reported here is the unique reactivity profile of the IBiox ligand family in the Pd0-catalyzed intramolecular arylation of such nonactivated secondary C?H bonds. Chiral C2-symmetric IBiox ligands led to high enantioselectivities for a broad range of valuable indane products containing a tertiary stereocenter, as well as the arylation of secondary C?H bonds adjacent to amides. Depending on the amide substituents and upon control of reaction time, indanes containing labile tertiary stereocenters were also obtained with high enantioselectivities. Analysis of the steric maps of the IBiox ligands indicated that the level of enantioselectivity correlates with the difference between the two most occupied and the two less occupied space quadrants, and provided a blueprint for the design of even more efficient ligands.
Enantio- and Diastereodivergent Sequential Catalysis Featuring Two Transition-Metal-Catalyzed Asymmetric Reactions
Abel-Snape, Xavier,Lautens, Mark,Masson-Makdissi, Jeanne,Prieto, Liher
supporting information, p. 16932 - 16936 (2021/07/02)
This study demonstrates the feasibility and inherent benefits of combining two distinct asymmetric transition-metal-catalyzed reactions in one pot. The reported transformation features a Pd-catalyzed asymmetric allylic alkylation and a Rh-catalyzed enantioselective 1,4-conjugate addition, effectively converting simple allyl enol carbonate precursors into enantioenriched cyclic ketones with two remote stereocenters. Despite the anticipated challenges associated with controlling stereoselectivity in such a complex system, the products are obtained in enantiomeric excesses ranging up to >99 % ee, exceeding those obtained from either of the individual asymmetric reactions. In addition, since the stereoselectivity of both steps is under catalyst control, this one-pot reaction is enantio- and diastereodivergent, enabling facile access to all stereoisomers from the same set of starting materials.
Application of proteasome inhibitor in inhibition of novel coronavirus
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Paragraph 0130; 0140-0142; 0162; 0172-0174, (2021/06/22)
The invention provides application of a proteasome inhibitor in inhibition of a novel coronavirus or preparation of novel coronavirus inhibitors. The proteasome inhibitor has a structure represented by a formula (I) or isomers, pharmaceutically acceptable salts thereof and prodrugs thereof. According to the application, by applying the proteasome inhibitor to inhibition of the novel coronavirus, good inhibiting activity is obtained, and a novel treatment way of think is provided for diseases such as pneumonia caused by the novel coronavirus.
Data mining of amine dehydrogenases for the synthesis of enantiopure amino alcohols
Guo, Jinggong,Li, Jun-Kuan,Ma, Jun-An,Miao, Yuchen,Qu, Ge,Sun, Zhoutong,Wang, Hongyue
, p. 5945 - 5952 (2020/10/08)
Chiral amino alcohols are essential building blocks for the pharmaceutical industry, and are widely present in natural and synthetic bioactive compounds. Amine dehydrogenases (AmDHs) can asymmetrically reduce prochiral ketones with low-cost ammonia to chiral amines and water as by-products, using NAD(P)H as a cofactor under mild conditions, but hydroxy ketones with formation of chiral hydroxy amines have rarely been investigated. In this study, six new bacterial AmDHs derived from amino acid dehydrogenases (AADHs) were identified by data mining, and five out of the six enzymes were able to efficiently reduce 1-hydroxybutan-2-one (1a) to (S)-2-aminobutan-1-ol ((S)-2a) with 19-99% conversions and 99% ee. The five AmDHs were purified and biochemically characterized for reductive amination activity towards substrate 1a with the optimal pH at 8.5 or 9.0 and the optimal temperature at 45 °C, 50 °C or 55 °C, and provided reductive amination of a broad range of prochiral α-hydroxy ketones, and even of a model β-hydroxy ketone leading to β-hydroxy amine with 99% ee. Our study expands the toolbox of AmDHs in the synthesis of chiral amino alcohols.
Copper(I) Phosphinooxazoline Complexes: Impact of the Ligand Substitution and Steric Demand on the Electrochemical and Photophysical Properties
Frey, Wolfgang,Giereth, Robin,Karnahl, Michael,Klo?, Marvin,Mengele, Alexander K.,Steffen, Andreas,Tschierlei, Stefanie
, p. 2675 - 2684 (2020/03/04)
A series of seven homoleptic CuI complexes based on hetero-bidentate P^N ligands was synthesized and comprehensively characterized. In order to study structure–property relationships, the type, size, number and configuration of substituents at the phosphinooxazoline (phox) ligands were systematically varied. To this end, a combination of X-ray diffraction, NMR spectroscopy, steady-state absorption and emission spectroscopy, time-resolved emission spectroscopy, quenching experiments and cyclic voltammetry was used to assess the photophysical and electrochemical properties. Furthermore, time-dependent density functional theory calculations were applied to also analyze the excited state structures and characteristics. Surprisingly, a strong dependency on the chirality of the respective P^N ligand was found, whereas the specific kind and size of the different substituents has only a minor impact on the properties in solution. Most importantly, all complexes except C3 are photostable in solution and show fully reversible redox processes. Sacrificial reductants were applied to demonstrate a successful electron transfer upon light irradiation. These properties render this class of photosensitizers as potential candidates for solar energy conversion issues.
Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases
Chen, Fei-Fei,Cosgrove, Sebastian C.,Birmingham, William R.,Mangas-Sanchez, Juan,Citoler, Joan,Thompson, Matthew P.,Zheng, Gao-Wei,Xu, Jian-He,Turner, Nicholas J.
, p. 11813 - 11818 (2019/12/02)
Chiral vicinal amino alcohols are an important motif found in many biologically active molecules. In this study, biocatalytic reductive amination of α-hydroxy ketones with ammonia was investigated using engineered amine dehydrogenases (AmDHs) derived from the leucine amino acid dehydrogenase (AADH) from Lysinibacillus fusiformis. The AmDHs thus identified enabled the synthesis of (S)-configured vicinal amino alcohols from the corresponding α-hydroxy ketones in up to 99% conversions and >99% ee. One of the AmDH variants was used to prepare a key intermediate for the antituberculosis pharmaceutical ethambutol.
Chiral resolution method for preparation of high-purity mono-configuration leucine
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Paragraph 0017; 0018, (2019/10/01)
The invention relates to a chiral resolution method for preparation of high-purity mono-configuration leucine. The method comprises the specific steps: (1) using (1R, 2R)-1,2-cyclohexanediamine as a precursor, and performing multistep derivation so as to prepare a catenane chiral resolution agent; (2) dissolving racemic leucine in a mixed solution of ethanol and water, mixing the solution with thechiral resolution agent and copper chloride which have the same molar amount as mono-configuration leucine, and precipitating a solid; (3) performing rotary evaporation under reduced pressure so as to remove ethanol in the mixed solution, performing extraction with ethyl acetate, and concentrating the filtrate so as to obtain optically pure dextro-leucine with an ee value of 98.0% or above; and (4) dissolving the precipitated solid in the step (3) in deionized water, performing extraction with ethyl acetate, and concentrating the filtrate so as to obtain optically pure L-leucine with an ee value of 99.0% or above. The method has the advantages that the synthesis method of the catenane chiral resolution agent is simple, and has a high yield of chiral resolution, the separated leucine has ahigh optical purity, and the method has easy large-scale chiral resolution.
Catalytic Mechanism Study on the 1,2- and 1,4-Transfer Hydrogenation of Ketimines and β-Enamino Esters Catalyzed by Axially Chiral Biscarboline-Based Alcohols
Dong, Mengxian,Wang, Jie,Wu, Shijie,Zhao, Yang,Ma, Yangyang,Xing, Yongfei,Cao, Fei,Li, Longfei,Li, Zhenqiu,Zhu, Huajie
supporting information, p. 4602 - 4610 (2019/08/30)
Axial N-O alcohols, which have two large carboline moieties connected to the axis were synthesized and used in catalytic enantioselective 1,2- and 1,4-transfer hydrogenations of total 26 ketimines and β-enamino esters. Excellent levels of enantioselectivity ranging from 91% to 99% were achieved by using catalyst (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. Interestingly, a mixture of (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide and (aR)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide was also able to provide high enantioselectivities up to 95% that is the same as that using pure (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. A plausible catalytic mechanism was suggested and total four kinds of transition states (TS) including almost 60 TS structures were investigated using density functional theory (DFT) with different basis sets such as 6-311G(2d,p). The predicted activation energy data are consistent with the experimental results. (Figure presented.).
Designing chiral amido-oxazolines as new chelating ligands devoted to direct Cu-catalyzed oxidation of allylic C–H bonds in cyclic olefins
Samadi, Saadi,Jadidi, Khosrow,Samadi, Mojgan,Ashouri, Akram,Notash, Behrouz
, p. 862 - 867 (2019/01/08)
A new type of amido-oxazoline ligands was conveniently synthesized from inexpensive and commercially available materials in high yields and enantiomeric excesses. The corresponding chiral copper complexes with this class of ligands [C2 symmetric S,S-bis(amido-oxazoline-Cu(II) complex] were synthesized accordingly. The ORTEP diagram of ligand 6a and complex 6a-copper were compared and characterization of the complex confirmed the involvement of both dentate parts of the ligands, the oxygen and nitrogen atoms, in complexation with copper. The utilization of this amido-oxazoline ligands in the copper-catalyzed enantioselective esterification of allylic C–H bonds of cyclic olefins with tert-butyl-4-nitrobenzoperoxoate resulted in the highest activities, yields (up to 95%) and enantioselectivities (up to 96%) in the presence of HZSM-5 zeolite. These new findings highlight the protocol as one of the most attractive and useful methods for the oxidation of the asymmetric allylic C–H bond of cycloalkenes compared to other methodologies reported in the literature.
