- PRACTICAL PREPARATION OF OPTICALLY ACTIVE O-BENZYLGLYCIDOL FROM OPTICALLY ACTIVE EPICHLOROHYDRIN
-
Practical preparation of optically active O-benzylglycidol has been developed starting from optically active epichlorohydrin by employing either basic or acidic conditions in the key stage.
- Takano, Seiichi,Sekiguchi, Yoshinori,Setoh, Masaki,Yoshimitsu, Takehiko,Inomata, Kohei,et al.
-
-
Read Online
- Design, Synthesis, and Structural Analysis of Cladosporin-Based Inhibitors of Malaria Parasites
-
Here we have described a systematic structure activity relationship (SAR) of a set of compounds inspired from cladosporin, a tool compound that targets parasite (Plasmodium falciparum) lysyl tRNA synthetase (KRS). Four sets of analogues, synthesized based on point changes in the chemical scaffold of cladosporin and other logical modifications and hybridizations, were assessed using high throughput enzymatic and parasitic assays along with in vitro pharmacokinetics. Co-crystallization of the most potent compound in our series (CL-2) with PfKRS revealed its structural basis of enzymatic binding and potency. Further, we report that CL-2 has performed better than cladosporin in terms of metabolic stability. It thus represents a new lead for further optimization toward the development of antimalarial drugs. Collectively, along with a lead compound, the series offers insights on how even the slightest chemical modification might play an important role in enhancing or decreasing the potency of a chemical scaffold.
- Babbar, Palak,Das, Pronay,Manickam, Yogavel,Mankad, Yash,Yadav, Swati,Parvez, Suhel,Sharma, Amit,Reddy, D. Srinivasa
-
p. 1777 - 1794
(2021/05/10)
-
- Discovery of a Potent and Selective Chikungunya Virus Envelope Protein Inhibitor through Computer-Aided Drug Design
-
The worldwide expansion of chikungunya virus (CHIKV) into tropical and subtropical areas in the last 15 years has posed a currently unmet need for vaccines and therapeutics. The E2-E1 envelope glycoprotein complex binds receptors on the host cell and promotes membrane fusion during CHIKV entry, thus constituting an attractive target for the development of antiviral drugs. In order to identify CHIKV antivirals acting through inhibition of the envelope glycoprotein complex function, our first approach was to search for amenable druggable sites within the E2-E1 heterodimer. We identified a pocket located in the interface between E2 and E1 around the fusion loop. Then, via a structure-based virtual screening approach and in vitro assay of antiviral activity, we identified compound 7 as a specific inhibitor of CHIKV. Through a lead optimization process, we obtained compound 11 that demonstrated increased antiviral activity and low cytotoxicity (EC50 1.6 μM, CC50 56.0 μM). Molecular dynamics simulations were carried out and described a possible interaction pattern of compound 11 and the E1-E2 dimer that could be useful for further optimization. As expected from target site selection, compound 11 inhibited virus internalization during CHIKV entry. In addition, virus populations resistant to compound 11 included mutation E2-P173S, which mapped to the proposed binding pocket, and second site mutation E1-Y24H. Construction of recombinant viruses showed that these mutations conferred antiviral resistance in the parental background. Finally, compound 11 presents acceptable solubility values and is chemically and enzymatically stable in different media. Altogether, these findings uncover a suitable pocket for the design of CHIKV entry inhibitors with promising antiviral activity and pharmacological profiles.
- álvarez, Diego E.,Battini, Leandro,Bollini, Mariela,Fidalgo, Daniela M.
-
p. 1503 - 1518
(2021/06/28)
-
- Facile microwave-assisted synthesis and antitubercular evaluation of novel aziridine derivatives
-
Novel 2-(aryloxymethyl)aziridines and 2-((3-aryl-1-phenylallyloxy)methyl)aziridine derivatives were prepared via ring-opening reaction of epoxides. The synthesized derivatives were characterized by using elemental analysis (EA), FT-IR, 13C NMR, and 1H NMR. The in vitro antitubercular activities of the synthesized compounds were evaluated against Mycobacterium tuberculosis H37Rv (MTB H37Rv) strain using MTT-MABA assay. All the aziridine derivatives exhibited improved persuasive antitubercular activity against MTB H37Rv in comparison with standard drugs. Among the tested compounds, 2-(naphthalene-1-yloxy) methyl aziridine (5b), 2-(naphthalene-2-yloxy)methylaziridine (5c), 2-(m-tolyloxymethyl)aziridine (5e), 2-(3-(4-methoxyphenyl)-1-phenylalloxy)methylaziridine (12b) and 2-(3-(2-chlorophenyl)-1-phenylallyloxy)methylaziridine (12c) revealed promising activity against MTB H37Rv. Specifically, compound 5b and 12 b showed three-times more active (MIC = 0.5 μg/mL) than the standard drugs ethambutol (MIC = 1.56 μg/mL) and ciprofloxacin (MIC = 1.56 μg/mL).
- Sarojini, Perumal,Jeyachandran, Malaichamy,Sriram, Dharmarajan,Ranganathan, Palraj,Gandhimathi
-
-
- An Amphiphilic (salen)Co Complex – Utilizing Hydrophobic Interactions to Enhance the Efficiency of a Cooperative Catalyst
-
An amphiphilic (salen)Co(III) complex is presented that accelerates the hydrolytic kinetic resolution (HKR) of epoxides almost 10 times faster than catalysts from commercially available sources. This was achieved by introducing hydrophobic chains that increase the rate of reaction in one of two ways – by enhancing cooperativity under homogeneous conditions, and increasing the interfacial area under biphasic reaction conditions. While numerous strategies have been employed to increase the efficiency of cooperative catalysts, the utilization of hydrophobic interactions is scarce. With the recent upsurge in green chemistry methods that conduct reactions ‘on water’ and at the oil-water interface, the introduction of hydrophobic interactions has potential to become a general strategy for enhancing the catalytic efficiency of cooperative catalytic systems. (Figure presented.).
- Solís-Mu?ana, Pablo,Salam, Joanne,Ren, Chloe Z.-J.,Carr, Bronte,Whitten, Andrew E.,Warr, Gregory G.,Chen, Jack L.-Y.
-
supporting information
p. 3207 - 3213
(2021/06/01)
-
- Engineering a homochiral metal-organic framework based on an amino acid for enantioselective separation
-
A chiral metal-organic framework possessing an open amphiphilic channel is constructed from a dicarboxylate ligand derived from an amino acid and is shown to be an efficient and recyclable chiral solid adsorbent, which is capable of separating racemic secondary alcohols, epoxides, and ibuprofen with very high enantioselectivity.
- Tang, Haitong,Yang, Keke,Wang, Kun-Yu,Meng, Qi,Wu, Fan,Fang, Yu,Wu, Xiang,Li, Yougui,Zhang, WenCheng,Luo, Yunfei,Zhu, Chengfeng,Zhou, Hong-Cai
-
p. 9016 - 9019
(2020/08/17)
-
- A new monooxygenase from: Herbaspirillum huttiense catalyzed highly enantioselective epoxidation of allylbenzenes and allylic alcohols
-
Asymmetric epoxidation is a green route to enantiopure epoxides, but often suffers from low enantioselectivity toward unconjugated terminal alkenes. Mining of the NCBI non-redundant protein sequences with a reconstructed ancestral sequence based on six st
- Lin, Hui,Tang, Yanhong,Dong, Shuang,Lang, Ruibo,Chen, Hongge
-
p. 2145 - 2151
(2020/04/17)
-
- Highly regio- and enantio-selective hydrolysis of two racemic epoxides by GmEH3, a novel epoxide hydrolase from Glycine max
-
A novel epoxide hydrolase from Glycine max, designated GmEH3, was excavated based on the computer-aided analysis. Then, gmeh3, a GmEH3-encoding gene, was cloned and successfully expressed in E. coli Rosetta(DE3). Among the ten investigated rac-epoxides, GmEH3 possessed the highest and best complementary regioselectivities (regioselectivity coefficients, αS = 93.7% and βR = 97.2%) in the asymmetric hydrolysis of rac-m-chlorostyrene oxide (5a), and the highest enantioselectivity (enantiomeric ratio, E = 55.6) towards rac-phenyl glycidyl ether (7a). The catalytic efficiency (kcatS/KmS = 2.50 mM?1 s?1) of purified GmEH3 for (S)-5a was slightly higher than that (kcatR/KmR = 1.52 mM?1 s?1) for (R)-5a, whereas the kcat/Km (5.16 mM?1 s?1) for (S)-7a was much higher than that (0.09 mM?1 s?1) for (R)-7a. Using 200 mg/mL wet cells of E. coli/gmeh3 as the biocatalyst, the scale-up enantioconvergent hydrolysis of 150 mM rac-5a at 25 °C for 1.5 h afforded (R)-5b with 90.2% eep and 95.4% yieldp, while the kinetic resolution of 500 mM rac-7a for 2.5 h retained (R)-7a with over 99% ees and 43.2% yields. Furthermore, the sources of high regiocomplementarity of GmEH3 for (S)- and (R)-5a as well as high enantioselectivity towards rac-7a were analyzed via molecular docking (MD) simulation.
- Zhang, Chen,Li, Chuang,Zhu, Xiu-xiu,Liu, You-yi,Zhao, Jun,Wu, Min-chen
-
p. 2795 - 2803
(2020/09/01)
-
- Chemoselective Epoxidation of Allyloxybenzene by Hydrogen Peroxide Over MFI-Type Titanosilicate
-
The chemoselective synthesis of 2-(phenoxymethyl)oxirane from allyloxybenzene is achieved with over 90 % yield in a sustainable reaction system using titanium-substituted silicalite-1 (TS-1) as a catalyst, hydrogen peroxide (H2O2) as an oxidant, and a mixture of MeOH/MeCN as a solvent at 40 °C. No acid-catalyzed side reactions prompted by the Lewis acidity of the Ti active site in TS-1 are observed. The TS-1 catalyst can also promote the formation of oxiranes from various p-substituted allyloxybenzenes in good yields. The reaction mechanism is investigated through the reaction with other allyloxy compounds. The results, which are supported by DFT calculations, indicate that an active species of Ti peroxides formed from the reaction of TS-1 with H2O2 selectively oxidizes the allyloxybenzene to 2-(phenoxymethyl)oxirane.
- Fujitani, Tadahiro,Hong, Dachao,Ito, Satoru,Ji, Xinyi,Kon, Yoshihiro,Nakashima, Takuya,Osuga, Ryota,Sato, Kazuhiko,Yokoi, Toshiyuki
-
-
- Sustainable Synthesis of a Potent and Selective 5-HT7Receptor Antagonist Using a Mechanochemical Approach
-
A mechanochemical procedure was developed to obtain PZ-1361, a potent and selective 5-HT7 receptor antagonist, with antidepressant properties in rodents. The elaborated protocol offered several advantages over classical batch synthesis, including improvement of the overall yield (from 34% to 64%), reduction of reaction time (from 60 to 5.5 h), limitation of the use of toxic solvents, and the formation of byproducts. This approach represents a rare example of the synthesis of biologically active compounds exclusively performed using mechanochemical reactions.
- Canale, Vittorio,Frisi, Valeria,Bantreil, Xavier,Lamaty, Frédéric,Zajdel, Pawe?
-
p. 10958 - 10965
(2020/09/18)
-
- Visible-light assisted of nano Ni/g-C3N4 with efficient photocatalytic activity and stability for selective aerobic C?H activation and epoxidation
-
A selective, economical, and ecological protocol has been described for the oxidation of methyl arenes and their analogs to the corresponding carbonyl compounds and epoxidation reactions of alkenes with molecular oxygen (O2) or air as a green oxygen source, under mild reaction conditions. The nano Ni/g-C3N4 exhibited high photocatalytic activity, stability, and selectivity in the C?H activation of methyl arenes, methylene arenes, and epoxidation of various alkenes under visible- light irradiation without the use of an oxidizing agent and under base free conditions.
- Akrami, Zahra,Hosseini-Sarvari, Mona
-
supporting information
(2020/10/13)
-
- Improving the activity and enantioselectivity of PvEH1, a Phaseolus vulgaris epoxide hydrolase, for o-methylphenyl glycidyl ether by multiple site-directed mutagenesis on the basis of rational design
-
Substrate spectrum assay exhibited that PvEH1, which is an epoxide hydrolase from P. vulgaris, had the highest specific activity and enantiomeric ratio (E) for racemic o-methylphenyl glycidyl ether (rac-1) among tested aryl glycidyl ethers (1–5). To produce (R)-1 via kinetic resolution of rac-1 efficiently, the catalytic properties of PvEH1 were further improved on the basis of rational design. Firstly, the seven single-site variants of PvEH1-encoding gene (pveh1) were PCR-amplified as designed, and expressed in E. coli BL21(DE3). Among all expressed single-site mutants, PvEH1L105I and PvEH1V106I had the highest specific activities of 17.6 and 16.4 U/mg protein, respectively, while PvEH1L196D had an enhanced E value of 9.2. Secondly, to combine their respective merits, one triple-site variant, pveh1L105I/V106I/L196D, was also amplified, and expressed. The specific activity, E value, and catalytic efficiency of PvEH1L105I/V106I/L196D were 23.1 U/mg, 10.9, and 6.65 mM?1 s?1, respectively, which were 2.0-, 1.8- and 2.4-fold higher than those of wild-type PvEH1. The source of PvEH1L105I/V106I/L196D with enhanced E value for rac-1 was preliminarily analyzed by molecular docking simulation. Finally, the scale-up kinetic resolution of 100 mM rac-1 was conducted using 5 mg wet cells/mL E. coli/pveh1L105I/V106I/L196D at 25 °C for 1.5 h, producing (R)-1 with 95.0% ees, 32.1% yield and 3.52 g/L/h space-time yield.
- Li, Chuang,Kan, Ting-Ting,Hu, Die,Wang, Ting-Ting,Su, Yong-Jun,Zhang, Chen,Cheng, Jian-Qing,Wu, Min-Chen
-
-
- Exploring the Biocatalytic Scope of a Novel Enantioselective Halohydrin Dehalogenase from an Alphaproteobacterium
-
A gene encoding halohydrin dehalogenase from an alphaproteobacterium (AbHHDH) was identified, cloned and over-expressed in Escherichia coli. AbHHDH was able to catalyze the stereoselective dehalogenation of prochiral and racemic halohydrins. It showed the highest enantioselectivity in the dehalogenation of 20?mM (R,S)-2-bromo-1-phenylethanol, which yielded (S)-2-bromo-1-phenylethanol with 99% ee and 34.5% yield. Moreover, AbHHDH catalyzed the azidolysis of epoxides with low to moderate (S)-enantioselectivity. The highest enantioselectivity (E = 18.6) was observed when (R,S)-benzyl glycidyl ether was used as the substrate. A sequential kinetic resolution catalyzed by HHDH was employed for the synthesis of chiral 1-chloro-3-phenoxy-2-propanol. We prepared enantiopure (S)-isomer with a high enantiopurity of ee > 99% and a yield of 30.7% (E-value: 21.3) by kinetic resolution of 20?mM substrate. The (S)-isomer with 99% ee readily obtained from 40 to 150?mM (R,S)-1-chloro-3-phenoxy-2-propanol. Taken together, the results of this study demonstrate the applicability of this HHDH for the production of optically active compounds. [Figure not available: see fulltext.].
- Xue, Feng,Ya, Xiangju,Xiu, Yuansong,Tong, Qi,Wang, Yuqi,Zhu, Xinhai,Huang, He
-
p. 629 - 637
(2019/01/25)
-
- Synthesis, Characterization, and Evaluation of Surface and Thermal Properties and Cytotoxicity of 2-Hydroxy-3-Phenoxypropyl Imidazolium Bola-Type Gemini Amphiphiles
-
A library of imidazolium-based gemini cationic bola amphiphiles was synthesized using a regioselective ring-opening reaction of glycidyl phenyl ether with imidazole under solvent-free conditions. The corresponding hexafluorophosphate (PF6?) and tetrafluoroborate (BF4?) counterion-containing amphiphiles were also synthesized and characterized using nuclear magnetic resonance (NMR) and mass spectroscopy. The micellar and interfacial parameters like the critical micelle concentration (CMC), surface pressure at the CMC (Пcmc), surface tension at CMC (γcmc), counterion binding (β), maximum surface excess concentration (Γmax), minimum area per molecule (Amin), standard free energy of micellization (ΔG0mic) and adsorption (ΔG0ads), and Kraft temperature were evaluated using surface tension and conductometry methods in aqueous solution as well as in buffer solution. Dynamic light scattering (DLS) was used to determine the size of the micelles formed in the aqueous solution. Cytotoxicity tests were carried out on the C6 glioma cancerous brain cell line using the MTT assay (3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyltetrazolium bromide) to evaluate the IC50 value of all the synthesized amphiphiles. Thermal stability of these amphiphiles was also evaluated using a thermal gravimetric analyzer (TGA). Economic way of synthesis, moderate thermal stability, a low value of CMC, and cytotoxicity of these amphiphiles will inspire new research in the field of nanobiotechnology and pharmaceutical industries.
- Aggarwal, Rajni,Singh, Sukhprit,Saini, Vedangana,Kaur, Gurcharan
-
-
- Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H1 antagonize activities
-
To improve the anti-inflammatory activity of desloratadine, we designed and synthesized a series of novel desloratadine derivatives. All compounds were evaluated for their anti-inflammatory and H1 antagonistic activities. Among them, compound 2c showed the strongest H1 antagonistic and anti-inflammatory activity. It also exhibited promising pharmacokinetic profiles and low toxicity. All these results suggest that compound 2c as a novel anti-allergic agent is worthy of further investigation.
- Li, Feng,Xu, Qinlong,Zhu, Qihua,Chu, Zhaoxing,Lin, Gaofeng,Mo, Jiajia,Zhao, Yan,Li, Jiaming,He, Guangwei,Xu, Yungen
-
-
- A facile and efficient method for synthesis of β-iodocarboxylates from terminal epoxides
-
A facile and efficient method has been developed for synthesis of β-iodocarboxylates in the presences of Ph3P/I2. Starting from epoxides, a series of β-iodocarboxylate compounds can be directly obtained in toluene media with excellent yields. Moreover, the method was successfully applied for the late-stage modification of natural products, such as isosteviol and vincamine derivatives, achieving the corresponding β-iodocarboxylates in good yields.
- Zhu, Ye-Fu,Wei, Bo-Le,Wang, Wen-Qiong,Xuan, Li-Jiang
-
supporting information
(2019/11/26)
-
- A novel homochiral metal-organic framework with an expanded open cage based on (: R)-3,3′-bis(6-carboxy-2-naphthyl)-2,2′-dihydroxy-1,1′-binaphthyl: synthesis, X-ray structure and efficient HPLC enantiomer separation
-
A new homochiral metal-organic framework (MOF) with an expanded open cage based on the (R)-3,3′-bis(6-carboxy-2-naphthyl)-2,2′-dihydroxy-1,1′-binaphthyl ligand was synthesized and utilized as a novel chiral stationary phase for high-performance liquid chromatography. Twelve racemates including sec-alcohols, sulfoxides, epoxides, lactone, 1,3-dioxolan-2-one, and oxazolidinone were used as analytes for evaluating the separation properties of the chiral-MOF-packed column. Experimentally, the homochiral MOF offered good molecular recognition ability, which suggests good prospects for the application of chiral MOFs as stationary phases for enantioseparation.
- Tanaka, Koichi,Kawakita, Tomohiro,Morawiak, Maja,Urbanczyk-Lipkowska, Zofia
-
p. 487 - 493
(2019/01/21)
-
- Enantioselective Resolution Copolymerization of Racemic Epoxides and Anhydrides: Efficient Approach for Stereoregular Polyesters and Chiral Epoxides
-
Herein we report an efficient strategy for preparing isotactic polyesters and chiral epoxides via enantioselective resolution copolymerization of racemic terminal epoxides with anhydrides, mediated by enantiopure bimetallic complexes in conjunction with a nucleophilic cocatalyst. The chirality of both the axial linker and the diamine backbones of the ligand are responsible for the chiral induction of this kinetic resolution copolymerization process. The catalyst systems exhibit exceptional levels of enantioselectivity with a kinetic resolution coefficient exceeding 300 for various racemic epoxides, affording highly isotactic copolymers (selectivity factors of more than 300) with a completely alternating structure and low polydispersity index. Most of the produced isotactic polyesters are typical semicrystalline materials with melting temperatures in the range from 77 to 160 °C.
- Li, Jie,Ren, Bai-Hao,Wan, Zhao-Qian,Chen, Shi-Yu,Liu, Ye,Ren, Wei-Min,Lu, Xiao-Bing
-
supporting information
p. 8937 - 8942
(2019/06/11)
-
- Chiral Bifunctional Metalloporphyrin Catalysts for Kinetic Resolution of Epoxides with Carbon Dioxide
-
Chiral binaphthyl-strapped Zn(II) porphyrins with triazolium halide units were synthesized as bifunctional catalysts for kinetic resolution of epoxides with CO2. Several catalysts were screened by changing the linker length and nucleophilic counteranions, and the optimized catalyst accelerated the enantioselective reaction at ambient temperature to produce optically active cyclic carbonates and epoxides.
- Maeda, Chihiro,Mitsuzane, Mayato,Ema, Tadashi
-
supporting information
p. 1853 - 1856
(2019/03/11)
-
- Calix[8]arene as New Platform for Cobalt-Salen Complexes Immobilization and Use in Hydrolytic Kinetic Resolution of Epoxides
-
Eight cobalt-salen complexes have been covalently attached to a calix[8]arene platform through a flexible linker by a procedure employing Click chemistry. The corresponding well-defined catalyst proved its efficiency in the hydrolytic kinetic resolution (HKR) of various epoxides through an operative bimetallic cooperative activation, demonstrating highly enhanced activity when compared to its monomeric analogue. As an insoluble complex, this multisite cobalt-salen catalyst could be easily recovered and reused in successive catalytic runs. Products were isolated by a simple filtration with virtually no cobalt traces and without requiring a prior purification by flash chromatography.
- Abdellah, Ibrahim,Martini, Cyril,Dos Santos, Amandine,Dragoe, Diana,Guérineau, Vincent,Huc, Vincent,Schulz, Emmanuelle
-
p. 4761 - 4767
(2018/10/02)
-
- Montmorillonite K10 catalyzed highly regioselective azidolysis of epoxides: A short and efficient synthesis of phenylglycine
-
A series of β‐hydroxyazides were effectively synthesized from the regioselective ring opening of epoxides by sodium azide using montmorillonite K10 as a novel heterogeneous catalyst in aqueous acetonitrile in good to excellent yields. The utility of this method has been demonstrated by achieving a short synthesis of phenylglycine in 33.5% overall yield.
- Ch Ghosh, Keshab,Banerjee, Isita,Sinha, Surajit
-
supporting information
p. 2923 - 2934
(2018/12/04)
-
- NBS/DMSO-mediated synthesis of (2,3-dihydrobenzo[b] [1,4]oxathiin-3-yl)methanols from aryloxymethylthiiranes
-
(2,3-Dihydrobenzo[b][1,4]oxathiin-3-yl)methanols were synthesized via reactions of aryloxymethylthiiranes and N-bromosuccinimide (NBS) in DMSO under microwave irradiation. The reaction mechanism was proposed as an intramolecular aromatic electrophilic substitution of 1-bromo-2-(aryloxymethyl)thiiran-1-iums, generated from aryloxymethylthiiranes and NBS, and the subsequent DMSO nucleophilic ring opening reaction of thiiran-1-iums followed by the water displacement. The current method provides a direct and simple strategy in the efficient preparation of (2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanols from readily available aryloxymethylthiiranes.
- Dong, Jun,Xu, Jiaxi
-
p. 9037 - 9044
(2018/06/08)
-
- Evaluating Ylehd, a recombinant epoxide hydrolase from: Yarrowia lipolytica as a potential biocatalyst for the resolution of benzyl glycidyl ether
-
Glycidyl ethers and their vicinal diols are important building blocks in the organic synthesis of anti-cancer and anti-obesity drugs. Ylehd, an epoxide hydrolase from tropical marine yeast Yarrowia lipolytica, was explored for its enantioselective propert
- Bendigiri, Chandrika,Harini,Yenkar, Sajal,Zinjarde, Smita,Sowdhamini,Ravikumar, Ameeta
-
p. 12918 - 12926
(2018/04/16)
-
- Asymmetric Hydrolytic and Aminolytic Kinetic Resolution of Racemic Epoxides using Recyclable Macrocyclic Chiral Cobalt(III) Salen Complexes
-
New chiral macrocyclic cobalt(III) salen complexes were synthesized and used as catalyst for the asymmetric kinetic resolution (AKR) of terminal epoxides and glycidyl ethers with aromatic/aliphatic amines and water as nucleophiles. This is the first occasion where a Co(III) salen complex demonstrated its ability to catalyze AKR as well as hydrolytic kinetic resolution (HKR) reactions. Excellent enantiomeric excesses of the epoxides, the corresponding amino alcohols and diols (upto 99%) with quantitative yields were achieved by using the chiral Co(III) salen complexes in dichloromethane at room temperature. This protocol was further extended for the synthesis of two important drug molecules, i.e., (S)-propranolol and (R)-naftopidil. The catalytic system was also explored for the synthesis of chirally pure diols and chiral cyclic carbonates using carbon dioxide as a greener renewable C1 source. The catalyst was recycled for upto 5 catalytic cycles with retention of enantioselectivity. (Figure presented.).
- Tak, Rajkumar,Kumar, Manish,Menapara, Tusharkumar,Gupta, Naveen,Kureshy, Rukhsana I.,Khan, Noor-ul H.,Suresh
-
supporting information
p. 3990 - 4001
(2017/11/22)
-
- Preparation method of beta-carboxyl phosphate
-
The invention provides a preparation method of beta-carboxyl phosphate. The preparation method comprises the following steps: carrying out regional selective ring-opening reaction on an epoxy compound and trialkyl phosphite to generate beta-carboxyl phosphate intermediate; and then oxidizing the beta-carboxyl phosphate intermediate to obtain the beta-carboxyl phosphate. The method is gentle in reaction condition and simple and convenient to operate without protection of an anhydrous solvent and oxygen, and is suitable for large-scale production. The beta-carboxyl phosphate synthesized by the preparation method can be used as an important intermediate synthesized by various misoprostols, such as travoprost, bimatoprost and tafluprost.
- -
-
Paragraph 0086; 0087
(2017/09/01)
-
- LSD1 Inhibitors
-
The present invention relates to compounds that inhibit LSD1 activity. In particular, the present invention relates to compounds, pharmaceutical compositions and methods of use, such as methods of treating cancer using the compounds and pharmaceutical compositions of the present invention.
- -
-
Paragraph 0312; 0313
(2017/07/14)
-
- Facile synthesis of thietanes via ring expansion of thiiranes
-
Thietanes are pharmaceutically important cores of some biological compounds and intermediates of organic synthesis. Various thietanes were prepared from thiiranes via ring expansion through a reaction with trimethyloxosulfonium iodide in the presence of sodium hydride. The reaction process is a nucleophilic ring-opening reaction of thiiranes with dimethyloxosulfonium methylide, generated from trimethyloxosulfonium iodide and sodium hydride, and subsequent intramolecular displacement (cyclization) of thiolates to the dimethyloxosulfonium moiety. The current method provides a new strategy for efficient preparation of thietanes from readily available thiiranes.
- Dong, Jun,Xu, Jiaxi
-
p. 836 - 844
(2017/02/05)
-
- Solvent-Directed Epoxide Opening with Primary Amines for the Synthesis of β-Amino Alcohols
-
An efficient synthesis of β-amino alcohols from a variety of epoxides and primary unbranched amines in the absence of any catalyst in high yields and regioselectivities is reported. A variety of polar mixed solvent systems allow for the selective formation of secondary amino alcohols over tertiary amino alcohols. The reaction scope extends to a wide variety of aromatic and aliphatic substituted epoxides and primary amines bearing complex functionality.
- Lizza, Joseph R.,Moura-Letts, Gustavo
-
supporting information
p. 1231 - 1242
(2017/03/11)
-
- A process for preparing phenyl glycidyl ether method (by machine translation)
-
A phenyl glycidyl ether synthesis method, including ring-opening reaction, ring-closing reaction, water washing, refining, to phenyl glycidyl ether thick vacuum recovering excess of epichlorohydrin, phenyl glycidyl ether to obtain the finished product, recovery of the ech directly in the next batch of recycling. The invention comprises to phenol, epoxy chloropropane as raw material, first of all in the N, N - dimethyl ethanolamine, tetrabutylammonium hydrosulfate and polyquaternary ammonium salt - 7 ternary composite catalyst under the action of the ring-opening reaction, to produce an intermediate phenyl chlorohydrin; then with the sodium hydroxide solution to the closed-loop by the reaction of the phenyl glycidyl ether. Recovery of the ech can direct the recycling; the invention has simple process, production cycle is short, the final product has high yield, high and whose small in color and the like, is easy to realize industrial. (by machine translation)
- -
-
Paragraph 0018; 0019
(2017/08/25)
-
- Rhenium complex-catalyzed Meinwald rearrangement reactions of oxiranes
-
The Meinwald rearrangement reaction of oxiranes to the corresponding carbonyl compounds is efficiently catalyzed by the ReBr(CO)5 complex.
- Umeda, Rui,Muraki, Masahito,Nakamura, Yuudai,Tanaka, Tomoyuki,Kamiguchi, Kyohei,Nishiyama, Yutaka
-
supporting information
p. 2393 - 2395
(2017/05/29)
-
- Multivariate Metal-Organic Frameworks as Multifunctional Heterogeneous Asymmetric Catalysts for Sequential Reactions
-
The search for versatile heterogeneous catalysts with multiple active sites for broad asymmetric transformations has long been of great interest, but it remains a formidable synthetic challenge. Here we demonstrate that multivariate metal-organic frameworks (MTV-MOFs) can be used as an excellent platform to engineer heterogeneous catalysts featuring multiple and cooperative active sites. An isostructural series of 2-fold interpenetrated MTV-MOFs that contain up to three different chiral metallosalen catalysts was constructed and used as efficient and recyclable heterogeneous catalysts for a variety of asymmetric sequential alkene epoxidation/epoxide ring-opening reactions. Interpenetration of the frameworks brings metallosalen units adjacent to each other, allowing cooperative activation, which results in improved efficiency and enantioselectivity over the sum of the individual parts. The fact that manipulation of molecular catalysts in MTV-MOFs can control the activities and selectivities would facilitate the design of novel multifunctional materials for enantioselective processes.
- Xia, Qingchun,Li, Zijian,Tan, Chunxia,Liu, Yan,Gong, Wei,Cui, Yong
-
supporting information
p. 8259 - 8266
(2017/06/28)
-
- Stereoselective Hydrolysis of Epoxides by reVrEH3, a Novel Vigna radiata Epoxide Hydrolase with High Enantioselectivity or High and Complementary Regioselectivity
-
To provide more options for the stereoselective hydrolysis of epoxides, an epoxide hydrolase (VrEH3) gene from Vigna radiata was cloned and expressed in Escherichia coli. Recombinant VrEH3 displayed the maximum activity at pH 7.0 and 45 °C and high stability at pH 4.5-7.5 and 55 °C. Notably, reVrEH3 exhibited high and complementary regioselectivity toward styrene oxides 1a-3a and high enantioselectivity (E = 48.7) toward o-cresyl glycidyl ether 9a. To elucidate these interesting phenomena, the interactions of the three-dimensional structure between VrEH3 and enantiomers of 1a and 9a were analyzed by molecular docking simulation. Using E. coli/vreh3 whole cells, gram-scale preparations of (R)-1b and (R)-9a were performed by enantioconvergent hydrolysis of 100 mM rac-1a and kinetic resolution of 200 mM rac-9a in the buffer-free water system at 25 °C. These afforded (R)-1b with >99% eep and 78.7% overall yield after recrystallization and (R)-9a with >99% ees, 38.7% overall yield, and 12.7 g/L/h space-time yield.
- Hu, Die,Tang, Cunduo,Li, Chuang,Kan, Tingting,Shi, Xiaoling,Feng, Lei,Wu, Minchen
-
p. 9861 - 9870
(2017/11/22)
-
- Synthesis of 2-(phenoxymethyl)oxirane derivatives through unexpected rearrangement of oxiran-2-ylmethyl benzenesulfonates
-
The synthesis of 2-(phenoxymethyl)oxirane derivatives from oxiran-2-ylmethyl benzenesulfonates was developed through a base promoted rearrangement. A new C-O bond was formed along with the unexpected cleavage of C-S bond via this process. This unusual reaction was characterized with mild reaction conditions, high efficiency, and excellent functional group tolerance. A plausible reaction mechanism was proposed on the basis of experimental results and control experiments.
- Shen, Chuang,Guo, Xiang,Yu, Jun,Zeng, Xian-Guo,Peng, Li,Zhao, Chuan-Meng,Zhang, Fu-Li
-
supporting information
p. 273 - 278
(2017/02/10)
-
- Asymmetric Transfer Hydrogenation of 1,3-Alkoxy/Aryloxy Propanones Using Tethered Arene/Ru(II)/TsDPEN Complexes
-
A series of propanones containing combinations of aryloxy and alkoxy substituents at the 1- and 3-positions were reduced to the alcohols via asymmetric transfer hydrogenation using a tethered Ru(II)/TsDPEN catalyst. The enantioselectivities of the reductions reveal a complex pattern of electronic and steric effects which, when used in a matched combination, can lead to the formation of products of up to 68% ee (84:16 er) from this highly challenging class of substrate.
- Forshaw, Sam,Matthews, Alexander J.,Brown, Thomas J.,Diorazio, Louis J.,Williams, Luke,Wills, Martin
-
supporting information
p. 2789 - 2792
(2017/06/07)
-
- Chiral Macrocyclic Organocatalysts for Kinetic Resolution of Disubstituted Epoxides with Carbon Dioxide
-
Among chiral macrocycles 1 synthesized, 1m with the 3,5-bis(trifluoromethyl)phenylethynyl group was the best organocatalyst for the enantioselective synthesis of cyclic carbonates from disubstituted or monosubstituted epoxides and CO2. The X-ray crystal structure of 1m revealed a well-defined chiral cavity with multiple hydrogen-bonding sites that is suitable for the enantioselective activation of epoxides. A catalytic cycle proposed was supported by DFT calculations.
- Ema, Tadashi,Yokoyama, Maki,Watanabe, Sagiri,Sasaki, Sota,Ota, Hiromi,Takaishi, Kazuto
-
supporting information
p. 4070 - 4073
(2017/08/15)
-
- Chemical modifications of lignin for the preparation of macromers containing cyclic carbonates
-
An epoxidized lignin derivative was prepared directly inserting epichlorohydrin on the phenolic functionalities. The epoxidized lignin was then converted to cyclic carbonates through the coupling reaction of CO2 with the oxirane rings. Imidazolium based ionic liquids, acting as both solvents and catalysts, were successfully employed in the carbonation reaction. Moreover, the ionic liquid was reused up to three times without significant loss in activity. Finally, an exhaustive spectroscopic characterization was carried out on the epoxidized and carbonated lignins by quantitative 31P and 13C NMR analyses.
- Salanti, Anika,Zoia, Luca,Orlandi, Marco
-
p. 4063 - 4072
(2016/07/21)
-
- From insertion to multicomponent coupling: Temperature dependent reactions of arynes with aliphatic alcohols
-
The temperature dependent selectivity switch in the reaction of arynes with aliphatic alcohols in THF has been reported. At -20°C, arynes smoothly insert into the O-H bond of alcohols to form alkyl aryl ethers. Interestingly, at 60°C, a highly selective multicomponent coupling occurs with the solvent THF acting as the nucleophilic trigger affording (4-(alkoxy)butoxy)arenes.
- Thangaraj, Manikandan,Bhojgude, Sachin Suresh,Mane, Manoj V.,Biju, Akkattu T.
-
supporting information
p. 1665 - 1668
(2016/01/30)
-
- Azidolysis of epoxides catalysed by the halohydrin dehalogenase from Arthrobacter sp. AD2 and a mutant with enhanced enantioselectivity: an (S)-selective HHDH
-
Halohydrin dehalogenase from Arthrobacter sp. AD2 catalysed azidolysis of epoxides with high regioselectivity and low to moderate (S)-enantioselectivity (E?=?1–16). Mutation of the asparagine 178 to alanine (N178A) showed increased enantioselectivity towards styrene oxide derivatives and glycidyl ethers. Conversion of aromatic epoxides was catalysed by HheA-N178A with complete enantioselectivity, however the regioselectivity was reduced. As a result of the enzyme-catalysed reaction, enantiomerically pure (S)-β-azido alcohols and (R)-α-azido alcohols (ee???99%) were obtained.
- Mikleu?evi?, Ana,Primo?i?, Ines,Hrenar, Tomica,Salopek-Sondi, Branka,Tang, Lixia,Elenkov, Maja Majeri?
-
p. 930 - 935
(2016/09/13)
-
- Chiral oligomers of spiro-salencobalt(III)X for catalytic asymmetric cycloaddition of epoxides with CO2
-
Several new chiral oligomers of spiro-salenCo(III)X (spiro = 1.1′-spirobiindane-7.7′-diol) complexes have been designed, synthesized, and characterized by nuclear magnetic resonance (NMR), infrared (IR), and elemental analyses, in which, the chiral spiro moieties are first introduced into a scaffold of chiral salenCo catalysts. They were used to catalyze the asymmetric cycloaddition of epoxides with carbon dioxide. Under very mild reaction conditions, a kinetic resolution of racemic epoxides with CO2 was smoothly initiated by these chiral oligomer catalysts with good enantioselectivities, which can be attributed to the match effect between chiral backbones of salen and spiro. High stability and easy recyclability are their major advantages.
- Zhu, Zhouhe,Zhang, Yuqian,Wang, Kai,Fu, Xiying,Chen, Fengjuan,Jing, Huanwang
-
-
- Synthesis of enantiopure epoxide by 'one pot' chemoenzymatic approach using a highly enantioselective dehydrogenase
-
Enantiopure α-phenethyl alcohols, including aromatic halohydrins, are important chiral building blocks. One of the best approaches to synthesise α-phenethyl alcohols is asymmetric reduction of prochiral ketones by alcohol dehydrogenases (ADHs). The obtained enantiopure halohydrin could be directly used to produce enantiopure epoxide through a base-induced ring-closure reaction, which is an attractive 'one pot' chemoenzymatic method for producing high-yield epoxide. In this study, a novel medium-chain dehydrogenase (KcDH) from Kuraishia capsulate CBS1993 was identified and characterised to show its broad substrate scope and excellent enantioselectivity. KcDH showed activities on 25 substrates of the 26 tested aromatic ketones and heteroaryl ketones, with an enantiomeric excess (ee) >99% and the highest relative activity observed with para-nitro acetophenone. Due to its high enantioselectivity for α-haloketones, a chemoenzymatic method for the synthesis of enantiopure styrene oxide (SO) and phenyl glycidyl ether (PGE) was developed through a base-induced ring-closure reaction on enantiopure halohydrin obtained with KcDH. (R)-SO and (S)-PGE were obtained in 86% and 94% analytical yield, respectively, and both epoxides were obtained with ee >99%. Thus, our results suggested that KcDH may be a promising biocatalyst for the production of multiple enantiopure α-phenethyl alcohols and epoxides.
- Wu, Kai,Chen, Lifeng,Fan, Haiyang,Zhao, Zhiqiang,Wang, Hualei,Wei, Dongzhi
-
p. 899 - 904
(2016/02/05)
-
- Continuous and convergent access to vicinyl amino alcohols
-
Five active pharmaceutical ingredients (APIs) containing the vicinyl amino alcohol moiety were synthesized using a convergent chemical assembly system. The continuous system is composed of four flow reaction modules: biphasic oxidation, Corey-Chaykovsky epoxidation, phenol alkylation, and epoxide aminolysis. Judicious choice of reagents and module order allowed for two classes of β-amino alcohols, aryl and aryloxy, to be synthesized in good (27-69%) overall yields.
- Nobuta, Tomoya,Xiao, Guozhi,Ghislieri, Diego,Gilmore, Kerry,Seeberger, Peter H.
-
p. 15133 - 15136
(2015/10/12)
-
- Hydroxy-directed, fluoride-catalyzed epoxide hydrosilylation for the synthesis of 1,4-diols
-
Abstract A novel highly regioselective, fluoride-catalyzed hydrosilylation of β-hydroxy epoxides has been developed. The reaction is modular and applicable to the synthesis of a broad range of 1,4-diols. Fluoride is crucial for two reasons: First, it promotes the formation of a silyl ether (which contains a Si-H bond) and, second, it enables ring opening by an intramolecular SN2 reaction through activation of the silane. The reaction can be performed under air. A modular, convergent, and stereoselective synthesis of 1,4-diols by epoxide hydrosilylation has been developed (see scheme). The reaction occurs under fluoride catalysis, is high yielding, highly regioselective, and can be carried out on a large scale.
- Zhang, Yong-Qiang,Funken, Nico,Winterscheid, Peter,Gans?uer, Andreas
-
supporting information
p. 6931 - 6934
(2015/06/08)
-
- Discovery of (phenoxy-2-hydroxypropyl)piperidines as a novel class of voltage-gated sodium channel 1.7 inhibitors
-
A novel class of NaV1.7 inhibitors has been identified by high-throughput screening followed by structure activity relationship studies. Among this series of compounds, piperidine 9o showed potent human and mouse NaV1.7 inhibitory activities with fair subtype selectivity over NaV1.5. Compound 9o successfully demonstrated analgesic efficacy in mice comparable to that of the currently used drug, mexiletine, but with an expanded central nervous system safety margin.
- Suzuki, Sayaka,Kuroda, Takeshi,Kimoto, Hiroko,Domon, Yuki,Kubota, Kazufumi,Kitano, Yutaka,Yokoyama, Tomihisa,Shimizugawa, Akiko,Sugita, Ryusuke,Koishi, Ryuta,Asano, Daigo,Tamaki, Kazuhiko,Shinozuka, Tsuyoshi,Kobayashi, Hiroyuki
-
p. 5419 - 5423
(2015/11/09)
-
- Chiral aziridine ring opening: facile synthesis of (R)-mexiletine and (R)-phenoxybenzamine hydrochloride
-
Abstract A simple and efficient synthesis of chiral drugs (R)-mexiletine 1, an anti-arrhythmic drug and (R)-phenoxybenzamine hydrochloride 2, an anti-hypertensive drug has been described via controlled reductive ring opening of chiral aziridine as a key step. The target compounds 1 and 2 were obtained in overall yields of 34% and 10.5%, respectively.
- Viswanadh,Velayudham,Jambu,Sasikumar,Muthukrishnan
-
p. 5269 - 5271
(2015/08/26)
-
- Synthesis, radiolabeling and in vivo evaluation of [11C](R)-1- [4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT7receptor
-
In the search for a novel serotonin 7 (5-HT7) receptor PET radioligand we synthesized and evaluated a new series of biphenylpiperazine derivatives in vitro. Among the studied compounds, (R)-1-[4-[2-(4-methoxyphenyl) phenyl]piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol ((R)-16), showed the best combination of affinity, selectivity, and lipophilicity, and was thus chosen for carbon-11 labelling and evaluation in pigs. After intravenous injection, [11C](R)-16 entered the pig brain and displayed reversible tracer kinetics. Pretreatment with the 5-HT7receptor selective antagonist SB-269970 (1) resulted in limited decrease in the binding of [11C](R)-16, suggesting that this radioligand is not optimal for imaging the brain 5-HT7receptor in vivo but it may serve as a lead compound for the design of novel 5-HT7receptor PET radioligands.
- Hansen, Hanne D.,Lacivita, Enza,Di Pilato, Pantaleo,Herth, Matthias M.,Lehel, Szabolcs,Ettrup, Anders,Andersen, Valdemar L.,Dyssegaard, Agnete,De Giorgio, Paola,Perrone, Roberto,Berardi, Francesco,Colabufo, Nicola Antonio,Niso, Mauro,Knudsen, Gitte M.,Leopoldo, Marcello
-
p. 152 - 163
(2014/05/06)
-
- Dioxomolybdenum(VI) complexes with naphtholate-oxazoline ligands in catalytic epoxidation of olefins
-
Synthesis, characterization and catalytic epoxidation experiments of two new dioxomolybdenum(VI) complexes [MoO2(L)2] (3a-b) equipped with O,N-bidentate naphtholate-oxazoline ligands L = 2a-b are described. Ligands 2a-b (2a = 2-(4,5-dihydrooxazol-2-yl)naphthalen-1-ol, 2b = 2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)naphthalen-1-ol) were obtained via a two-step synthesis starting from 1-hydroxy-naphthoic acid. Complexes 3a-b were synthesized starting from [MoO2(acac)2] and obtained in good yields as air and moisture stable solids. The molecular structure of both complexes 3a-b were determined by single crystal X-ray diffraction analysis, showing the expected octahedral coordination of the Mo center by two bidentate ligands of 2a or 2b and two terminal oxo ligands. Interestingly, for complex 3b two different coordination isomers with regards to the orientation of the bidentate ligands (N,N-trans 3b and N,N-cis 3b'), were obtained in the solid state. Both complexes 3a-b show high catalytic activities and selectivities in the epoxidation of various terminal and internal olefins at low catalyst loadings of 0.05 mol% with tert-butylhydroperoxide. With cyclooctene TON of 5000 could be reached, for styrene selectivities of >90% were achieved.
- Traar, Pedro,Schachner, J?rg A.,Stanje, Bernhard,Belaj, Ferdinand,M?sch-Zanetti, Nadia C.
-
-
- Asymmetric hydrolytic kinetic resolution with recyclable polymeric Co(iii)-salen complexes: A practical strategy in the preparation of (S)-metoprolol, (S)-toliprolol and (S)-alprenolol: Computational rationale for enantioselectivity
-
A series of chiral polymeric Co(iii)-salen complexes based on a number of achiral and chiral linkers were synthesized and their catalytic performances were assessed in the asymmetric hydrolytic kinetic resolution of terminal epoxides. The effects of the linker were judiciously studied and it was found that in the case of the chiral BINOL-based polymeric salen complex 1, there was an enrichment in catalyst reactivity and enantioselectivity of the unreacted epoxide, particularly in the case of short as well as long chain aliphatic epoxides. Good isolated yields of the unreacted epoxide (up to 46% compared to 50% theoretical yield) along with high enantioselectivity (up to 99%) were obtained in most cases using catalyst 1. Further studies showed that catalyst 1 could retain its catalytic activity for six cycles under the present reaction conditions without any significant loss in activity or enantioselectivity. To show the practical applicability of the above synthesized catalyst we have synthesised some potent chiral β-blockers in moderate yield and high enantioselectivity using complex 1. The DFT (M06-L/6-31+G??//ONIOM(B3LYP/6-31G?:STO-3G)) calculations revealed that the chiral BINOL linker influences the enantioselectivity achieved with Co(iii)-salen complexes. Further, the transition state calculations show that the R-BINOL linker with the (S,S)-Co(iii)-salen complex is energetically preferred over the corresponding S-BINOL linker with the (S,S)-Co(iii)-salen complex for the HKR of 1,2-epoxyhexane. The role of non-covalent C-H?π interactions and steric effects has been discussed to control the HKR reaction of 1,2-epoxyhexane.
- Roy, Tamal,Barik, Sunirmal,Kumar, Manish,Kureshy, Rukhsana I.,Ganguly, Bishwajit,Khan, Noor-Ul H.,Abdi, Sayed H. R.,Bajaj, Hari C.
-
p. 3899 - 3908
(2015/02/19)
-
- Heterobimetallic dual-catalyst systems for the hydrolytic kinetic resolution of terminal epoxides
-
A heterobimetallic dual-catalyst system based on the preparation and use of various salen complexes has been developed for the hydrolytic kinetic resolution (HKR) of terminal epoxides. A combination of cobalt-salen and manganese-salen complexes, generated from ligands with the same configuration possessing thiophene or pyrrole moieties, produced indeed highly selective catalysts for the hydrolysis of epibromohydrin. This effect could also be extended to other terminal epoxides and to the more challenging ring opening of cyclohexene oxide. Kinetic studies indicated that only one CoIII salen complex was involved in the rate-determining step, which supported a heterobimetallic highly enantioselective pathway based on the crucial existence of in situ generated CoIII-OH species, previously postulated in the literature. The beneficial effect of the presence of additional Mn-complexes was ascribed to the inhibition of the alternative less enantioselective monometallic reaction pathway by epoxide activation.
- Hong, Xiang,Mellah, Mohamed,Schulz, Emmanuelle
-
p. 2608 - 2617
(2014/07/22)
-
- A smart library of epoxide hydrolase variants and the top hits for synthesis of (S)-β-blocker precursors
-
Microtuning of the enzyme active pocket has led to a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical β-blocker precursors. Improved activities of 6- to 430-fold were achieved by redesigning the active site at two predicted hot spots. This study represents a breakthrough in protein engineering of epoxide hydrolases and resulted in enhanced activity toward bulky substrates. Hot pockets: Microtuning of the enzyme active pocket gives a smart library of epoxide hydrolase variants with an expanded substrate spectrum covering a series of typical β-blocker precursors. Improved activities of 6- to 430-fold were achieved by redesigning the active site at two predicted hot spots, and enhanced activity toward bulky substrates was found.
- Kong, Xu-Dong,Ma, Qian,Zhou, Jiahai,Zeng, Bu-Bing,Xu, Jian-He
-
supporting information
p. 6641 - 6644
(2014/07/08)
-
- A new synthesis of sultams from amino alcohols
-
The base-mediated cyclization of N,O-dimesylate derivatives of cyclic and acyclic amino alcohols provides a simple access to five- and six-member sultams: isothiazolidine-1,1-dioxides and thiazinane-1,1-dioxides respectively.
- Lad, Nitin,Sharma, Rajiv,Marquez, Victor E.,Mascarenhas, Malcolm
-
p. 6307 - 6309
(2013/11/06)
-
- Dioxidomolybdenum(VI) complexes containing ligands with the bipyrrolidine backbone as efficient catalysts for olefin epoxidation
-
Air-stable chiral dioxidomolybdenum(VI) complexes of the type [MoO 2(L)] (L = L12-; 1, L = L22-, 2) were prepared by the reaction of [MoO2Cl2] with the bis(phenol) ligands 1,4-bis(2-hydroxy-benzyl)-(S,S)-2,2′-bipyrrolidine [(S,S)-H2L1] and 1,4-bis(2-hydroxy-3,5-di-tert-butylbenzyl)-(S,S)-2,2′-bipyrrolidine [(S,S)-H2L2). They were characterized by NMR spectroscopy, mass spectrometry, elemental analysis, and single-crystal X-ray diffraction analysis, which revealed a distorted octahedral coordination geometry around the molybdenum(VI) center with a cis-α configuration. The Mo-Ooxo bond lengths are almost equal and vary only between 1.701 and 1.7091 A. Complexes 1 and 2 were found to be efficient and selective catalysts for various olefin epoxidation reactions. Catalyst loadings of 0.5 mol-%, the use of 2 equiv. of oxidant (tert-butyl hydroperoxide), as well as unchanged catalyst performance over three consecutive catalytic runs demonstrate the excellent stability of the catalysts. Various challenging substrates including 1-octene or limonene were converted selectively to their corresponding epoxides. However, no asymmetric induction was observed. The cis-α isomers of dioxidomolybdenum complexes with a chiral backbone exhibit higher catalytic epoxidation activity than the related cis-β complexes. Copyright
- Mayilmurugan, Ramasamy,Traar, Pedro,Schachner, Joerg A.,Volpe, Manuel,Moesch-Zanetti, Nadia C.
-
p. 3664 - 3670
(2013/07/26)
-