5978-70-1Relevant academic research and scientific papers
Pickering-Droplet-Derived MOF Microreactors for Continuous-Flow Biocatalysis with Size Selectivity
Liang, Linfeng,Shi, Hu,Tian, Danping,Wang, Jun-Hao,Xue, Nan,Yang, Hengquan,Zhang, Xiaoming
supporting information, p. 16641 - 16652 (2021/10/20)
Enzymatic microarchitectures with spatially controlled reactivity, engineered molecular sieving ability, favorable interior environment, and industrial productivity show great potential in synthetic protocellular systems and practical biotechnology, but their construction remains a significant challenge. Here, we proposed a Pickering emulsion interface-directed synthesis method to fabricate such a microreactor, in which a robust and defect-free MOF layer was grown around silica emulsifier stabilized droplet surfaces. The compartmentalized interior droplets can provide a biomimetic microenvironment to host free enzymes, while the outer MOF layer secludes active species from the surroundings and endows the microreactor with size-selective permeability. Impressively, the thus-designed enzymatic microreactor exhibited excellent size selectivity and long-term stability, as demonstrated by a 1000 h continuous-flow reaction, while affording completely equal enantioselectivities to the free enzyme counterpart. Moreover, the catalytic efficiency of such enzymatic microreactors was conveniently regulated through engineering of the type or thickness of the outer MOF layer or interior environments for the enzymes, highlighting their superior customized specialties. This study provides new opportunities in designing MOF-based artificial cellular microreactors for practical applications.
Structure of the fungal hydroxylase, CYP505A30, and rational transfer of mutation data from CYP102A1 to alter regioselectivity
Aschenbrenner, Jasmin C.,Ebrecht, Ana C.,Opperman, Diederik J.,Smit, Martha S.,Tolmie, Carmien
, p. 7359 - 7367 (2021/11/23)
CYP505A30 is a fungal, self-sufficient cytochrome P450 monooxygenase that can selectively oxyfunctionalisen-alkanes, fatty alcohols, and fatty acids. From alkanes, it produces a mixture of non-vicinal diols by two sequential hydroxylation reactions. Here we report the structure of the haem domain of CYP505A30, the first structure for a member of the CYP505 family, with dodecanoic acid bound within the active site. Overall, a high structural similarity to the related bacterial CYP102A1 was observed, despite low sequence identity (a high degree of conservation with only two amino acid differences close to the haem. Stabilisation of the fatty acid substrate in CYP505A30 also occurs, as in CYP102A1,viaan arginine residue. However, compared to R47, which is situated in the β1 region of CYP102A1, R358 is located in the β3 region of CYP505A30. We furthermore created mutants to test if it is possible to rationally transfer the knowledge on active site mutations in CYP102A1 to change the regioselectivity of CYP505A30. The introduction of F93V, I334F mutations resulted in increased ω-1 (C2) regioselectivity, similar to CYP102A1 87-328, of more than 80% forn-octane and 90% forn-decane. Changing residues to resemble the CYP102A1 wildtype increased the regioselectivity towards ω-2 (C3) to over 60% for both substrates. The knowledge gained from this study unlocks a more selective production of symmetrical non-vicinal diols fromn-alkanes.
Amino Acid-Functionalized Metal-Organic Frameworks for Asymmetric Base–Metal Catalysis
Newar, Rajashree,Akhtar, Naved,Antil, Neha,Kumar, Ajay,Shukla, Sakshi,Begum, Wahida,Manna, Kuntal
supporting information, p. 10964 - 10970 (2021/03/29)
We report a strategy to develop heterogeneous single-site enantioselective catalysts based on naturally occurring amino acids and earth-abundant metals for eco-friendly asymmetric catalysis. The grafting of amino acids within the pores of a metal-organic framework (MOF), followed by post-synthetic metalation with iron precursor, affords highly active and enantioselective (>99 % ee for 10 examples) catalysts for hydrosilylation and hydroboration of carbonyl compounds. Impressively, the MOF-Fe catalyst displayed high turnover numbers of up to 10 000 and was recycled and reused more than 15 times without diminishing the enantioselectivity. MOF-Fe displayed much higher activity and enantioselectivity than its homogeneous control catalyst, likely due to the formation of robust single-site catalyst in the MOF through site-isolation.
Production of chiral alcohols from racemic mixtures by integrated heterogeneous chemoenzymatic catalysis in fixed bed continuous operation
Carceller, Jose Miguel,Climent, Maria J.,Corma, Avelino,Iborra, Sara,Mifsud, Maria
, p. 2767 - 2777 (2020/06/17)
Valuable chiral alcohols have been obtained from racemic mixtures with an integrated heterogeneous chemoenzymatic catalyst in a two consecutive fixed catalytic bed continuous reactor system. In the first bed the racemic mixture of alcohols is oxidized to the prochiral ketone with a Zr-Beta zeolite and using acetone as the hydrogen acceptor. In the second catalytic bed the prochiral ketone is stereoselectively reduced with an alcohol dehydrogenase (ADH) immobilized on a two dimensional (2D) zeolite. In this process, the alcohol (isopropanol) formed by the reduction of acetone in the first step reduces the cofactor in the second step, and the full reaction cycle is in this way internally closed with 100% atom economy. A conversion of about 95% with ～100% selectivity to either the (R) or the (S) alcohol has been obtained for a variety of racemic mixtures of alcohols.
Chiral Imidazo[1,5- a]pyridine-Oxazolines: A Versatile Family of NHC Ligands for the Highly Enantioselective Hydrosilylation of Ketones
Chinna Ayya Swamy,Varenikov, Andrii,Ruiter, Graham De
supporting information, p. 247 - 257 (2020/02/04)
Herein we report the synthesis and application of a versatile class of N-heterocyclic carbene ligands based on an imidazo[1,5-a]pyridine-3-ylidine backbone that is fused to a chiral oxazoline auxiliary. The key step in the synthesis of these ligands involves the installation of the oxazoline functionality via a microwave-assisted condensation of a cyano-azolium salt with a wide variety of 2-amino alcohols. The resulting chiral bidentate NHC-oxazoline ligands form stable complexes with rhodium(I) that are efficient catalysts for the enantioselective hydrosilylation of structurally diverse ketones. The corresponding secondary alcohols are isolated in good yields (typically >90%) with good to excellent enantioselectivities (80-93% ee). The reported hydrosilylation occurs at ambient temperatures (40 °C), with excellent functional group tolerability. Even ketones bearing heterocyclic substituents (e.g., pyridine or thiophene) or complex organic architectures are hydrosilylated efficiently, which is discussed further in this report.
Efficient Asymmetric Synthesis of Ethyl (S)-4-Chloro-3-hydroxybutyrate Using Alcohol Dehydrogenase SmADH31 with High Tolerance of Substrate and Product in a Monophasic Aqueous System
Chen, Rong,Liu, Qinghai,Wang, Hualei,Wei, Dongzhi,Xie, Youyu,Yang, Zeyu,Ye, Wenjie
, p. 1068 - 1076 (2020/07/06)
Bioreductions catalyzed by alcohol dehydrogenases (ADHs) play an important role in the synthesis of chiral alcohols. However, the synthesis of ethyl (S)-4-chloro-3-hydroxybutyrate [(S)-CHBE], an important drug intermediate, has significant challenges concerning high substrate or product inhibition toward ADHs, which complicates its production. Herein, we evaluated a novel ADH, SmADH31, obtained from the Stenotrophomonas maltophilia genome, which can tolerate extremely high concentrations (6 M) of both substrate and product. The coexpression of SmADH31 and glucose dehydrogenase from Bacillus subtilis in Escherichia coli meant that as much as 660 g L-1 (4.0 M) ethyl 4-chloroacetoacetate was completely converted into (S)-CHBE in a monophasic aqueous system with a >99.9% ee value and a high space-time yield (2664 g L-1 d-1). Molecular dynamics simulation shed light on the high activity and stereoselectivity of SmADH31. Moreover, five other optically pure chiral alcohols were synthesized at high concentrations (100-462 g L-1) as a result of the broad substrate spectrum of SmADH31. All these compounds act as important drug intermediates, demonstrating the industrial potential of SmADH31-mediated bioreductions.
METHODS OF MAKING HIGH ENANTIOSELECTIVE SECONDARY ALCOHOLS
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Paragraph 0098; 0099; 0109, (2020/09/08)
A new process to synthesis of compound OBI-3424 R-form and S-form products is provided. The "R-form" compound OBI-3423 was first synthesized with 48% overall yield from compound OBI-3424-5 by installation of the labile phosphate motif at later stage. The stereo chemistry is established by 5 steps chemo-enzyme combination synthesis to afford 99% optical purity, After then, the "S-form" compound OBI-3424 is prepared with improving overall yield of 54% from compound OBI-3424-5. The stereo chemistry is established by 4 steps combination of chemo-enzyme synthesis with excellent optical purity of 99%.
Asymmetric Transfer Hydrogenation in Thermomorphic Microemulsions Based on Ionic Liquids
Hejazifar, Mahtab,Pálv?lgyi, ádám Márk,Bitai, Jacqueline,Lanaridi, Olga,Bica-Schr?der, Katharina
, p. 1841 - 1851 (2019/10/11)
A thermomorphic ionic-liquid-based microemulsion system was successfully applied for the Ru-catalyzed asymmetric transfer hydrogenation of ketones. On the basis of the temperature-dependent multiphase behavior of the targeted microemulsion, simple product separation as well as catalyst recycling could be realized. The use of water-soluble ligands improved the immobilization of the catalyst in the microemulsion phase and significantly decreased the catalyst leaching into the organic layer upon extraction of the product. Eventually, the optimized microemulsion system could be applied to a wide range of aromatic ketones that were reduced with good isolated yields (up to 98%) and enantioselectivities (up to 97%), while aliphatic ketones were less successful.
Compartmentalized Nanoreactors for One-Pot Redox-Driven Transformations
Qu, Peiyuan,Kuepfert, Michael,Jockusch, Steffen,Weck, Marcus
, p. 2701 - 2706 (2019/03/08)
This contribution introduces poly(2-oxazoline)-based shell cross-linked micelles (SCMs) as nanoreactors to realize one-pot redox-driven deracemizations of secondary alcohols in aqueous media. TEMPO and Rh-TsDPEN moieties are spatially positioned into the hydrophilic corona and the hydrophobic micelle core, respectively. TEMPO catalyzes the oxidation of racemic secondary alcohols into ketones, while Rh-TsDPEN catalyzes the asymmetric transfer hydrogenation (ATH) of these ketones to afford enantioenriched secondary alcohols. Both catalysts, the Rh-TsDPEN complex and TEMPO, are incompatible with each other and the SCMs are designed to provide indispensable catalyst site isolation. Kinetic studies show that the SCMs enhance the reactivity of the immobilized catalysts, in comparison to those for the unsupported analogues under the same reaction conditions. Our nanoreactors can perform deracemizations on a broad range of secondary alcohol substrates and are reusable in a continuous manner while maintaining high activity.
One-Pot Absolute Stereochemical Identification of Alcohols via Guanidinium Sulfate Crystallization
Brummel, Beau R.,Lee, Kinsey G.,McMillen, Colin D.,Kolis, Joseph W.,Whitehead, Daniel C.
supporting information, p. 9622 - 9627 (2019/12/02)
A novel technique for the absolute stereochemical determination of alcohols has been developed that uses crystallization of guanidinium salts of organosulfates. The simple one-pot, two-step process leverages facile formation of guandinium organosulfate single crystals for the straightforward determination of the absolute stereochemistry of enantiopure alcohols by means of X-ray crystallography. The strong hydrogen bonding network drives the stability of the crystal lattice and allows for a diverse range of organic alcohol substrates to be analyzed.
