10593-35-8Relevant academic research and scientific papers
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)
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.
Seawater-Based Biocatalytic Strategy: Stereoselective Reductions of Ketones with Marine Yeasts
Serra, Immacolata,Guidi, Benedetta,Burgaud, Gaetan,Contente, Martina L.,Ferraboschi, Patrizia,Pinto, Andrea,Compagno, Concetta,Molinari, Francesco,Romano, Diego
, p. 3254 - 3260 (2016)
The large consumption of freshwater in fermentations and bio-transformations is a matter of concern for the sustainability of many bio-processes. The use of seawater to perform bio-processes is a sustainable alternative. In this work, we used marine yeasts from deep-sub-seafloor sediments grown in seawater as bio-catalysts to perform the stereoselective reduction of different ketones, and the bio-transformations were accomplished in seawater as well. Strains of Meyerozyma guilliermondii and Rhodotorula mucilaginosa were able to reduce different aromatic ketones with high molar conversions and moderate-to-high enantioselectivity with no significant differences between bio-catalysis performed in seawater and freshwater. Finally, the selected marine yeasts were used for the reduction of key intermediates in seawater for the synthesis of molecules of pharmaceutical interest (desogestrel, norgestrel, gestodene, pramipexole).
Novel dimethoxy(aminoalkoxy)borate derived from (S)-diphenylprolinol as highly efficient catalyst for the enantioselective boron-mediated reduction of prochiral ketones
Stepanenko, Viatcheslav,Ortiz-Marciales, Margarita,Barnes, Charles L.,Garcia, Carmelo
, p. 995 - 998 (2009)
The novel dimethoxyl(aminoalkoxy)borate 1 was isolated as a white crystalline dimer joined by H-bonding as evidenced by X-ray analysis, and demonstrated to be a highly effective catalyst for the asymmetric reduction of representative prochiral ketones with borane-DMS. Optically pure alcohols were obtained using only 1 mol % of catalyst 1 in up to 99% ee.
A Practical Method for Asymmetric Borane Reduction of Prochiral Ketones Using Chiral Amino Alcohols and Trimethyl Borate
Masui, Moriyasu,Shioiri, Takayuki
, p. 273 - 274 (1997)
A new method for the asymmetric borane reduction with reagents prepared in situ from chiral amino alcohols and trimethyl borate is described.
A solar light-driven, eco-friendly protocol for highly enantioselective synthesis of chiral alcohols via photocatalytic/biocatalytic cascades
Choudhury, Sumit,Baeg, Jin-Ook,Park, No-Joong,Yadav, Rajesh K.
, p. 4389 - 4400 (2014)
The judicious utilization of solar light for the asymmetric synthesis of optically active compounds by imitating natural photosynthesis introduces a new concept that harnesses this renewable energy in vitro for ultimate transformation into chiral chemical bonds. Herein, we present a comprehensive description of such a biomimetic endeavor towards the design and construction of an asymmetric artificial photosynthesis system that comprises an efficient method of nicotinamide cofactor (NADPH) regeneration under visible light employing a graphene-based light harvesting photocatalyst and its subsequent utilization in an enzyme-catalyzed asymmetric reduction of prochiral ketones to expediently furnish the corresponding chiral secondary alcohols. A detailed optimization study revealed a major dependency of the reaction outcome on the amount of cofactor, photocatalyst and enzyme used, as well as the mode of their addition. A series of structurally diverse ketones bearing an array of (hetero)aryl/alkyl substituents proved to be highly suitable to our photocatalytic-biocatalytic cascade approach, providing (R/S)-1-(hetero)aryl/ alkylethanols in excellent enantioselectivities (ee ～ 95->99.9%) under mild and environmentally benign conditions. To the best of our knowledge, the synthesis of these enantiopure alcohols employing a visible-light-driven nicotinamide cofactor regeneration strategy has been reported for the first time. Such enantioenriched alcohols act as versatile chiral building blocks for the synthesis of compounds having industrial and pharmaceutical relevance. In addition, this solar-to-chiral chemicals prototype appears advantageous from ecological and economical perspectives. We describe mechanistic pathways to demonstrate how the present catalytic synthesis protocol functions through perfect orchestration between visible-light-driven photocatalysis and biocatalysis to be successively applied in inducing asymmetry in an achiral molecule for the ultimate goal of solar energy utilization in the synthesis of valuable chiral fine chemicals. This work highlights the potential advantages of a bioinspired system to the pertinence of solar energy in asymmetric transformations leading to enantioenriched alcohol precursors, and thus opens up a new field of research that might emerge as an important breakthrough with promising implications towards generating a sustainable and non-fossil/non- nuclear energy future. the Partner Organisations 2014.
Asymmetric hydrogenation of simple ketones with planar chiral ruthenocenyl phosphinooxazoline ligands
Wang, Yanlan,Liu, Delong,Meng, Qinghua,Zhang, Wanbin
, p. 2510 - 2512 (2009)
Ruthenocenyl phosphinooxazoline ligands have been shown to be highly efficient catalysts in the asymmetric hydrogenation. Both simple aromatic and heteroaromatic ketones were examined and excellent conversions and enantioselectivities were achieved.
Highly enantioselective transfer hydrogenation of ketones with chiral (NH)2P2 Macrocyclic Iron(II) complexes
Bigler, Raphael,Huber, Raffael,Mezzetti, Antonio
, p. 5171 - 5174 (2014)
Bis(isonitrile) iron(II) complexes bearing a C2-symmetric diamino (NH)2P2 macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a broad scope of substrates (ketones, enones, and imines) in high yield (up to 99.5 %), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading (generally 0.1 mol %). The catalyst can be easily tuned by modifying the substituents of the isonitrile ligand. Paying the iron price: Bis(isonitrile) iron(II) complexes with a C2-symmetric diamino (NH)2P2 macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a broad scope of substrates (ketones, enones, imines) in high yield (up to 99.5 %), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading (generally 0.1 mol %).
Microbial Oxidation with Bacillus stearothermophilus: High Enantioselective Resolution of 1-Heteroaryl and 1-Aryl Alcohols
Fantin, Giancarlo,Fogagnolo, Marco,Medici, Alessandro,Pedrini, Paola,Poli, Silvia,Gardini, Fausto
, p. 1607 - 1612 (1993)
Key Words: Microbial oxidation, Enantioselective resolution, 1-Heteroarylethanol, 1-Arylethanol, 1-(2-Thienyl)cyclopropanemethanol, Bacillus stearothermophilus The enantioselective resolution of the racemic 1-heteroaryl- and 1-arylethanols 1a-h via microbial oxidation with Bacillus stearothermophilus to give the R-enantiomers with high enantiomeric excesses is described.The kinetic resolution of 1-(2-thienyl)ethanol 1b by oxidation with Acinetobacter calcoaceticus anitrat to S-enantiomer (ee 100percent) is also reported.
Chiral Cyclopentadienone iron complexes for the catalytic asymmetric hydrogenation of ketones
Gajewski, Piotr,Renom-Carrasco, Marc,Facchini, Sofia Vailati,Pignataro, Luca,Lefort, Laurent,De Vries, Johannes G.,Ferraccioli, Raffaella,Forni, Alessandra,Piarulli, Umberto,Gennari, Cesare
, p. 1887 - 1893 (2015)
Three chiral (cyclopentadienone)iron complexes derived from (R)-BINOL (CK1-3) were synthesized and their structures unambiguously confirmed by X-ray analysis (CK3). Under suitable conditions for the in situ conversion into the corresponding (hydroxycyclopentadienyl)iron hydrides (Me3NO, H2), the new chiral complexes were tested in the catalytic asymmetric hydrogenation of ketones, showing moderate to good enantioselectivity. In particular, the complex bearing methoxy substituents at the 3,3-positions of the binaphthyl moiety (CK2) proved remarkably more enantioselective than the unsubstituted one (CK1) and reached the highest level of enantioselectivity (up to 77% ee) ever obtained with chiral (cyclopentadienone)iron complexes. Reducto! Chiral (cyclopentadienone)iron complexes were synthesized and tested, after in situ activation, in the catalytic asymmetric hydrogenation of ketones leading to the highest enantiomeric excesses ever obtained with this type of catalysts.
3- and 4-pyridylalkyl adamantanecarboxylates: Inhibitors of human cytochrome P450(17α) (17α-hydroxylase/C17,20-lyase). Potential nonsteroidal agents for the treatment of prostatic cancer
Chan, Ferdinand C. Y.,Potter, Gerard A.,Barrie, S. Elaine,Haynes, Benjamin P.,Rowlands, Martin G.,Houghton, John,Jarman, Michael
, p. 3319 - 3323 (1996)
Various 3- and 4-pyridylalkyl 1-adamantanecarboxylates have been synthesized and tested for inhibitory activity toward the 17α-hydroxylase and C17,20-lyase activities of human testicular cytochrome P450(17α). The 4-pyridylalkyl esters were much more inhibitory than their 3- pyridylalkyl counterparts. The most potent was (S)-1-(4-pyridyl)ethyl 1- adamantanecarboxylate (3b; IC50 for lyase, 1.8 nM), whereas the (R)- enantiomer 3a was much less inhibitory (IC50 74 nM). Nearly as potent as 3b was the dimethylated counterpart, the 2-(4-pyridylpropan-2-yl) ester 5 (IC50 2.7 nM), which was also more resistant to degradation by esterases. In contrast to their 4-pyridyl analogs, the enantiomers of the 1-(3- pyridyl)ethyl ester were similarly inhibitory (IC50 for lyase; (R)-isomer 8a 150 nM, (S)-isomer 8b 230 nM). Amides corresponding to the 4- pyridylmethyl ester 1 and the (S)-1-(4-pyridyl)ethyl ester 3b, respectively 11 and 15b, were much less inhibitory than their ester counterparts. On the basis of a combination of inhibitory potency and resistance to esterases, the ester 5 was the best candidate for further development as a potential nonsteroidal inhibitor of cytochrome P450(17α) for the treatment of prostate cancer.
