4276-75-9Relevant academic research and scientific papers
HPLC separation of 2-aryloxycarboxylic acid enantiomers on chiral stationary phases
Charushin, V. N.,Chulakov, E. N.,Krasnov, V. P.,Levit, G. L.,Sadretdinova, L. Sh.,Tumashov, A. A.,Vakarov, S. A.
, p. 900 - 907 (2021/06/07)
The possibility for separating enantiomers of a number of practically significant 2-aryloxycarboxylic acids was studied by normal- and reversed-phase HPLC on popular chiral stationary phases. The best separation parameters were achieved on the chiral phases with the polysaccharide base Chiralcel OD-H and Chiralpack AD under the normal-phase HPLC conditions. The (S)- and (R)-enantiomers of 2-(1-naphthyloxy)- and 2-(2-iodophenoxy)propionic acids with enantiomeric excess ee >99% were isolated using preparative chiral HPLC.
Access to Optically Enriched α-Aryloxycarboxylic Esters via Carbene-Catalyzed Dynamic Kinetic Resolution and Transesterification
Liu, Bin,Song, Runjiang,Xu, Jun,Majhi, Pankaj Kumar,Yang, Xing,Yang, Song,Jin, Zhichao,Chi, Yonggui Robin
supporting information, p. 3335 - 3338 (2020/04/30)
Optically active α-aryloxycarboxylic acids and their derivatives are important functional molecules. Disclosed here is a carbene-catalyzed dynamic kinetic resolution and transesterification reaction for access to this class of molecules with up to 99% yields and 99:1 er values. Addition of a chiral carbene catalyst to the ester substrate leads to two diastereomeric azolium ester intermediates that can quickly epimerize to each other and thus allows for effective dynamic kinetic resolution to be realized. The optically enriched ester products from our reaction can be quickly transformed to chiral herbicides and other bioactive molecules.
Structural insights into the differences among lactisole derivatives in inhibitory mechanisms against the human sweet taste receptor
Nakagita, Tomoya,Matsuya, Takumi,Narukawa, Masataka,Misaka, Takumi,Kobayashi, Takuya,Ishida, Akiko,Hashimoto, Makoto,Hirokawa, Takatsugu
, (2019/04/13)
Lactisole, an inhibitor of the human sweet taste receptor, has a 2-phenoxypropionic acid skeleton and has been shown to interact with the transmembrane domain of the T1R3 subunit (T1R3-TMD) of the receptor. Another inhibitor, 2,4-DP, which shares the same molecular skeleton as lactisole, was confirmed to be approximately 10-fold more potent in its inhibitory activity than lactisole; however the structural basis of their inhibitory mechanisms against the receptor remains to be elucidated. Crystal structures of the TMD of metabotropic glutamate receptors, which along with T1Rs are categorized as class C G-protein coupled receptors, have recently been reported and made it possible to create an accurate structural model for T1R3-TMD. In this study, the detailed structural mechanism underlying sweet taste inhibition was characterized by comparing the action of lactisole on T1R3-TMD with that of 2,4-DP. We first performed a series of experiments using cultured cells expressing the sweet taste receptor with mutations and examined the interactions with these inhibitors. Based on the results, we next performed docking simulations and then applied molecular dynamics-based energy minimization. Our analyses clearly revealed that the (S)-isomers of both lactisole and 2,4-DP, interacted with the same seven residues in T1R3-TMD and that the inhibitory potencies of those inhibitors were mainly due to stabilizing interactions mediated via their carboxyl groups in the vertical dimension of the ligand pocket of T1R3-TMD. In addition, 2,4-DP engaged in a hydrophobic interaction mediated by its o-Cl group, and this interaction may be chiefly responsible for the higher inhibitory potency of 2,4-DP.
Mutual Kinetic Resolution of Racemic 3,4-Dihydro-3-methyl-2H-[1,4]benzoxazines with Acyl Chlorides of Racemic O-Phenyllactic Acids and DFT Modelling of Transition States
Korolyova, Marina A.,Vakarov, Sergey A.,Kozhevnikov, Dmitry N.,Gruzdev, Dmitry A.,Levit, Galina L.,Krasnov, Victor P.
, p. 4577 - 4585 (2018/09/06)
The effect of the electronic nature of the para substituent on the aromatic ring of 2-aryloxypropionyl chlorides on the stereochemical outcome of the acylation of 3,4-dihydro-3-methyl-2H-[1,4]benzoxazine and its 7,8-difluoro-containing analogue has been studied. The geometries of the diastereoisomeric transition states and the corresponding Gibbs free enthalpies of activation were determined through DFT calculations at the COSMO-CH2Cl2-B3LYP-D3-gCP/def2-TZVP (or def2-SVP)//B3LYP-D3-gCP/def2-SVP level of theory. It has been found that a low-cost quantum chemical calculation at a chosen level of theory describes well the quantitative dependence of the selectivity of acylation on the structures of the reagents. The obtained results indicate that aromatic interactions between the reagents play a significant role in the process of stereodifferentiation, ensuring high selectivity of the acylation of benzoxazines with 2-aryloxyacyl chlorides.
Alkali-sensitive ring opening cucurbituril and application thereof
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Paragraph 0017; 0018, (2018/08/04)
The invention discloses alkali-sensitive ring opening cucurbituril. A structural formula of the alkali-sensitive ring opening cucurbituril is shown. The alkali-sensitive ring opening cucurbituril hasthe advantages that the alkali-sensitive ring opening cucurbituril can be used as a supermolecular medicine carrier and is provided with large ring cryptand with inner cavities, the ring rigidity of large rings can be reduced by means of ring opening, and accordingly the alkali-sensitive ring opening cucurbituril is extremely high in host-guest bonding capacity; the alkali-sensitive ring opening cucurbituril is excellent in alkali sensitivity, contains carboxylic acid groups and can be used as the medicine carrier to be widely applied to medicine delivery paths, and the water solubility and the stability of insoluble medicines can be greatly improved; the alkali-sensitive ring opening cucurbituril can be used as an alkali-sensitive carrier, medicines can be released in alkaline environments such as small intestines in human bodies, accordingly, effects of releasing the medicines in a sustained and controlled manner can be realized, and irritation of the medicines on gastric mucosas canbe prevented.
Highly Enantioselective Hydrogenation of Amides via Dynamic Kinetic Resolution Under Low Pressure and Room Temperature
Rasu, Loorthuraja,John, Jeremy M.,Stephenson, Elanna,Endean, Riley,Kalapugama, Suneth,Clément, Roxanne,Bergens, Steven H.
supporting information, p. 3065 - 3071 (2017/03/11)
High-throughput screening and lab-scale optimization were combined to develop the catalytic system trans-RuCl2((S,S)-skewphos)((R,R)-dpen), 2-PrONa, and 2-PrOH. This system hydrogenates functionalized α-phenoxy and related amides at room temperature under 4 atm H2 pressure to give chiral alcohols with up to 99% yield and in greater than 99% enantiomeric excess via dynamic kinetic resolution.
A 2 - (4-methoxyphenoxy) process for industrial production of sodium propionate
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Paragraph 0029; 0030, (2016/10/07)
The invention relates to the technical field of a preparation method of a compound, and especially relates to an industrial production method of a sweetness inhibitor 2-(4-methoxyphenoxy)sodium propionate. The method comprises the following steps: taking methoxyphenol and methyl 2-chloropropionate as raw materials, under the effect of sodium hydroxide and a catalyst, taking water as a solvent, reacting for 6-24 hours at the temperature of 60-90 DEG C to obtain the product 2-(4-methoxyphenoxy)propionic acid; placing the 2-(4-methoxyphenoxy)propionic acid and sodium hydroxide in ethanol, heating, and reacting to obtain 2-(4-methoxyphenoxy)sodium propionate. According to the invention, water is taken as a solvent, the impurity in the generated product can be effectively removed, the synthesis and purification treatment processes are simple, the purity of the product is high, and the industrial production method is suitable for industrial production of 2-(4-methoxyphenoxy)sodium propionate.
Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5′-monophosphate dehydrogenase
Gorla, Suresh Kumar,Kavitha, Mandapati,Zhang, Minjia,Chin, James En Wai,Liu, Xiaoping,Striepen, Boris,Makowska-Grzyska, Magdalena,Kim, Youngchang,Joachimiak, Andrzej,Hedstrom, Lizbeth,Cuny, Gregory D.
, p. 4028 - 4043 (2013/06/27)
Cryptosporidium parvum is an enteric protozoan parasite that has emerged as a major cause of diarrhea, malnutrition, and gastroenteritis and poses a potential bioterrorism threat. C. parvum synthesizes guanine nucleotides from host adenosine in a streamlined pathway that relies on inosine 5′-monophosphate dehydrogenase (IMPDH). We have previously identified several parasite-selective C. parvum IMPDH (CpIMPDH) inhibitors by high-throughput screening. In this paper, we report the structure-activity relationship (SAR) for a series of benzoxazole derivatives with many compounds demonstrating CpIMPDH IC50 values in the nanomolar range and >500-fold selectivity over human IMPDH (hIMPDH). Unlike previously reported CpIMPDH inhibitors, these compounds are competitive inhibitors versus NAD +. The SAR study reveals that pyridine and other small heteroaromatic substituents are required at the 2-position of the benzoxazole for potent inhibitory activity. In addition, several other SAR conclusions are highlighted with regard to the benzoxazole and the amide portion of the inhibitor, including preferred stereochemistry. An X-ray crystal structure of a representative E·IMP·inhibitor complex is also presented. Overall, the secondary amine derivative 15a demonstrated excellent CpIMPDH inhibitory activity (IC 50 = 0.5 ± 0.1 nM) and moderate stability (t1/2 = 44 min) in mouse liver microsomes. Compound 73, the racemic version of 15a, also displayed superb antiparasitic activity in a Toxoplasma gondii strain that relies on CpIMPDH (EC50 = 20 ± 20 nM), and selectivity versus a wild-type T. gondii strain (200-fold). No toxicity was observed (LD 50 > 50 μM) against a panel of four mammalian cells lines.
Design, synthesis, and pharmacological effects of structurally simple ligands for MT1 and MT2 melatonin receptors
Carocci, Alessia,Catalano, Alessia,Lovece, Angelo,Lentini, Giovanni,Duranti, Andrea,Lucini, Valeria,Pannacci, Marilou,Scaglione, Francesco,Franchini, Carlo
experimental part, p. 6496 - 6511 (2010/10/02)
A series of phenoxyalkyl and phenylthioalkyl amides were prepared as melatoninergic ligands. Modulation of affinity of the newly synthesized compound by applying SARs around the terminal amide moiety, the alkyl chain, and the methoxy group on the aromatic ring provides compounds with nanomolar affinity for both melatonin receptor subtypes. Affinity towards MT1 and MT2 receptors were modulated also exploiting chirality. The investigation of intrinsic activity revealed that all the tested compounds behave as full or partial agonists.
A great improvement of the enantioselectivity of lipase-catalyzed hydrolysis and esterification using co-solvents as an additive
Nishigaki, Tomohiro,Yasufuku, Yoshitaka,Murakami, Sayuri,Ebara, Yasuhito,Ueji, Shin-Ichi
experimental part, p. 617 - 622 (2009/04/11)
Addition of co-solvents such as tetrahydrofuran resulted in a great improvement of the enantioselectivity of lipase-catalyzed hydrolysis of butyl 2-(4-substituted phenoxy)propanoates in an aqueous buffer solution. On the other hand, lipase lyophilized from an aqueous solution containing the co-solvents catalyzed highly enantioselective esterification of 2-(4-substituted phenoxy)propionic acids, 2-(4-isobutylphenyl)propionic acid (ibuprofen), and 2-(6-methoxy-2-naph-thyl)propionic acid (naproxen) in an organic solvent. An increase in the E value up to two orders of magnitude was observed for some substrates. The origin of the enantioselectivity enhancement caused by the co-solvent addition was mainly attributed to a significant deceleration in the initial reaction rate for the incorrectly binding enantiomer, as compared with that for the correctly binding enantiomer. From the results of FT-1R, CD, and ESR spectra, the co-solvent addition was also found to bring about a partial destruction of the tertiary structure of lipase.
