88496-71-3Relevant academic research and scientific papers
Efficient asymmetric synthesis of chiral alcohols using high 2-propanol tolerance alcohol dehydrogenase: Sm ADH2 via an environmentally friendly TBCR system
Yang, Zeyu,Fu, Hengwei,Ye, Wenjie,Xie, Youyu,Liu, Qinghai,Wang, Hualei,Wei, Dongzhi
, p. 70 - 78 (2020/01/21)
Alcohol dehydrogenases (ADHs) together with the economical substrate-coupled cofactor regeneration system play a pivotal role in the asymmetric synthesis of chiral alcohols; however, severe challenges concerning the poor tolerance of enzymes to 2-propanol and the adverse effects of the by-product, acetone, limit its applications, causing this strategy to lapse. Herein, a novel ADH gene smadh2 was identified from Stenotrophomonas maltophilia by traditional genome mining technology. The gene was cloned into Escherichia coli cells and then expressed to yield SmADH2. SmADH2 has a broad substrate spectrum and exhibits excellent tolerance and superb activity to 2-propanol even at 10.5 M (80%, v/v) concentration. Moreover, a new thermostatic bubble column reactor (TBCR) system is successfully designed to alleviate the inhibition of the by-product acetone by gas flow and continuously supplement 2-propanol. The organic waste can be simultaneously recovered for the purpose of green synthesis. In the sustainable system, structurally diverse chiral alcohols are synthesised at a high substrate loading (>150 g L-1) without adding external coenzymes. Among these, about 780 g L-1 (6 M) ethyl acetoacetate is completely converted into ethyl (R)-3-hydroxybutyrate in only 2.5 h with 99.9% ee and 7488 g L-1 d-1 space-time yield. Molecular dynamics simulation results shed light on the high catalytic activity toward the substrate. Therefore, the high 2-propanol tolerance SmADH2 with the TBCR system proves to be a potent biocatalytic strategy for the synthesis of chiral alcohols on an industrial scale.
Synthesis of Thelepamide via Catalyst-Controlled 1,4-Addition of Cysteine Derivatives and Structure Revision of Thelepamide
Seitz, Tobias,Millán, Ramón E.,Lentz, Dieter,Jiménez, Carlos,Rodríguez, Jaime,Christmann, Mathias
supporting information, p. 594 - 597 (2018/02/10)
The first enantioselective total synthesis and structural reassignment of (-)-thelepamide, a cytotoxic tetraketide-amino acid from the marine worm Thelepus crispus, is reported. A convergent approach provides access to all thelepamide diastereomers in six steps from four simple building blocks. Key features of the synthesis include the application of Melchiorre's organocatalytic thia-Michael reaction and a sonication-assisted assembly of an unprecedented N,O-acetal-hemiacetal moiety. The corrected structure was confirmed by NMR-DFT analysis.
Identification of a Robust Carbonyl Reductase for Diastereoselectively Building syn-3,5-Dihydroxy Hexanoate: A Bulky Side Chain of Atorvastatin
Gong, Xu-Min,Zheng, Gao-Wei,Liu, You-Yan,Xu, Jian-He
supporting information, p. 1349 - 1354 (2017/09/23)
t-Butyl-6-cyano-(3R,5R)-dihydroxyhexanoate is an advanced chiral precursor for the synthesis of the side chain pharmacophore of cholesterol-lowering drug atorvastatin. Herein, a robust carbonyl reductase (LbCR) was newly identified from Lactobacillus brevis, which displays high activity and excellent diastereoselectivity toward bulky t-butyl 6-cyano-(5R)-hydroxy-3-oxo-hexanoate (7). The engineered Escherichia coli cells harboring LbCR and glucose dehydrogenase (for cofactor regeneration) were employed as biocatalysts for the asymmetric reduction of substrate 7. As a result, as much as 300 g L-1 of water-insoluble substrate was completely converted to the corresponding chiral diol with >99.5% de in a space-time yield of 351 g L-1 d-1, indicating a great potential of LbCR for practical synthesis of the very bulky and bi-chiral 3,5-dihydroxy carboxylate side chain of best-selling statin drugs.
Study of Class i and Class III Polyhydroxyalkanoate (PHA) Synthases with Substrates Containing a Modified Side Chain
Jia, Kaimin,Cao, Ruikai,Hua, Duy H.,Li, Ping
, p. 1477 - 1485 (2016/05/09)
Polyhydroxyalkanoates (PHAs) are carbon and energy storage polymers produced by a variety of microbial organisms under nutrient-limited conditions. They have been considered as an environmentally friendly alternative to oil-based plastics due to their renewability, versatility, and biodegradability. PHA synthase (PhaC) plays a central role in PHA biosynthesis, in which its activity and substrate specificity are major factors in determining the productivity and properties of the produced polymers. However, the effects of modifying the substrate side chain are not well understood because of the difficulty to accessing the desired analogues. In this report, a series of 3-(R)-hydroxyacyl coenzyme A (HACoA) analogues were synthesized and tested with class I synthases from Chromobacterium sp. USM2 (PhaCCs and A479S-PhaCCs) and Caulobacter crescentus (PhaCCc) as well as class III synthase from Allochromatium vinosum (PhaECAv). It was found that, while different PHA synthases displayed distinct preference with regard to the length of the alkyl side chains, they could withstand moderate side chain modifications such as terminal unsaturated bonds and the azide group. Specifically, the specific activity of PhaCCs toward propynyl analogue (HHxyCoA) was only 5-fold less than that toward the classical substrate HBCoA. The catalytic efficiency (kcat/Km) of PhaECAv toward azide analogue (HABCoA) was determined to be 2.86 × 105 M-1 s-1, which was 6.2% of the value of HBCoA (4.62 × 106 M-1 s-1) measured in the presence of bovine serum albumin (BSA). These side chain modifications may be employed to introduce new material functions to PHAs as well as to study PHA biogenesis via click-chemistry, in which the latter remains unknown and is important for metabolic engineering to produce PHAs economically.
Identification of an ε-keto ester reductase for the efficient synthesis of an (R)-α-lipoic acid precursor
Zhang, Yu-Jun,Zhang, Wen-Xia,Zheng, Gao-Wei,Xu, Jian-He
supporting information, p. 1697 - 1702 (2015/06/02)
Abstract A novel reductase (CpAR2) with unusually high activity toward an ε-keto ester, ethyl 8-chloro-6-oxooctanoate, was isolated from Candida parapsilosis. The asymmetric reduction of ethyl 8-chloro-6-oxooctanoate using Escherichia coli cells coexpressing CpAR2 and glucose dehydrogenase genes gave ethyl (R)-8-chloro-6-hydroxyoctanoate, a key precursor for the synthesis of (R)-α-lipoic acid, in high space-time yield (530 gL-1d-1) and with excellent enantiomeric excess (>99%). This bioprocess was shown to be viable on a 10-L scale. This method provides a greener and more cost-effective method for the industrial production of (R)-α-lipoic acid.
Improving the toolbox of bioreductions by the use of continuous flow systems
Lopes, Raquel O.,Grimm, Simon,Ribeiro, Joyce B.,Leal, Ivana C. R.,Miranda, Leandro S. M.,De Souzae, Rodrigo O. M. A.
, p. 550 - 554 (2015/04/27)
Packed bed reactors can be used as an interesting alternative on the bioreduction of β-ketoesteres mediated by immobilized microorganisms. Here in, we report our results on the bioreduction of ethyl 3-oxohexanoate by immobilized Kluyveromyces marxianus cells and tert-butyl 3-oxobutanoate by immobilized Rhodotorula rubra cells under continuous flow conditions leading the desired β-hydroxy esters corresponding in high yields and enantiomeric excess.
Total synthesis of micromide: A marine natural product
Han, Jianrong,Lian, Jingtang,Tian, Xia,Zhou, Shengwei,Zhen, Xiaoli,Liu, Shouxin
, p. 7232 - 7238 (2015/02/19)
This paper describes an efficient procedure for the synthesis of micromide, a natural product that shows anti-solid-tumor activity. Our strategy involved the synthesis of N-nosyl-protected amino acids and their N-methylation with iodo-methane. The hindered oligopeptides containing N-methyl amino acids were synthesized in excellent yields and high purities.[ampi]]
Chiral amide from (1S, 2R)-(+)-norephedrine and furoic acid: An efficient catalyst for asymmetric Reformatsky reaction
Ananthi, Nallamuthu,Velmathi, Sivan
, p. 151 - 158 (2014/04/03)
Chiral amide derived from (1S, 2R)-(+)-norephedrine and 2-furoic acid was found to catalyse the asymmetric Reformatsky reaction between prochiral aldehydes and α-bromo ethylacetate with diethylzinc as zinc source. The corresponding chiral β-hydroxy esters were formed in 99% yield with over 80% enantiomeric excess. The presence of air was found to be essential for the effective C-C bond formation. The mechanism for the catalytic reaction was proposed. Indian Academy of Sciences.
ChenPhos: Highly modular P-stereogenic C1-symmetric diphosphine ligands for the efficient asymmetric hydrogenation of α-substituted cinnamic acids
Chen, Weiping,Spindler, Felix,Pugin, Benoit,Nettekoven, Ulrike
supporting information, p. 8652 - 8656 (2013/09/12)
These cats are purrfectionists: The ChenPhos ligands (see structure) showed dramatically higher catalytic activity in the title reaction than their C 2-symmetric predecessor with two dimethylaminoethyl-substituted ferrocenyl(phenyl)phosphanyl groups. The ready accessibility, extreme air stability, and high enantioselectivity, activity, and productivity of these ligands make them very promising for a wide range of practical applications. Copyright
Total syntheses of amphidinolides T1, T3, and T4
Clark, J. Stephen,Romiti, Filippo
supporting information, p. 10072 - 10075 (2013/10/01)
Concise and high-yielding total syntheses of amphidinolides T1, T3, and T4 have been completed using an alkynyl macrolactone as a common late-stage intermediate. The required α-hydroxy ketone motif was installed by sequential alkyne hydrosilylation, epoxidation, and Fleming-Tamao oxidation. An oxonium ylide rearrangement formed the trisubstituted tetrahydrofuran core found in the natural products.
