cas 99395-88-7, (S)-(+)-4-Phenyl-2-oxazolidinone

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Catalytic enantioselective synthesis of β-amino alcohols by nitrene insertion
Chiral β-amino alcohols are important building blocks for the synthesis of drugs, natural products, chiral auxiliaries, chiral ligands and chiral organocatalysts. The catalytic asymmetric β-amination of alcohols offers a direct strategy to access this class of molecules. Herein, we report a general intramolecular C(sp3)-H nitrene insertion method for the synthesis of chiral oxazolidin-2-ones as precursors of chiral β-amino alcohols. Specifically, the ring-closing C(sp3)-H amination of N-benzoyloxycarbamates with 2 mol% of a chiral ruthenium catalyst provides cyclic carbamates in up to 99% yield and with up to 99% ee. The method is applicable to benzylic, allylic, and propargylic C-H bonds and can even be applied to completely non-activated C (sp3)-H bonds, although with somewhat reduced yields and stereoselectivities. The obtained cyclic carbamates can subsequently be hydrolyzed to obtain chiral β-amino alcohols. The method is very practical as the catalyst can be easily synthesized on a gram scale and can be recycled after the reaction for further use. The synthetic value of the new method is demonstrated with the asymmetric synthesis of a chiral oxazolidin-2-one as intermediate for the synthesis of the natural product aurantioclavine and chiral β-amino alcohols that are intermediates for the synthesis of chiral amino acids, indane-derived chiral Box-ligands, and the natural products dihydrohamacanthin A and dragmacidin A.[Figure not available: see fulltext.].
Zhou, Zijun,Tan, Yuqi,Shen, Xiang,Ivlev, Sergei,Meggers, Eric
p. 452 - 458
(2020/12/31)

Preparation method of oxazolidinone compound
The preparation method comprises the following steps 1): dissolving aromatic amino acid in methanol, dissolving the aromatic amino acid in methanol, heating up to 50 - 60 °C heat preservation 1 - 2h, 2) reducing: adding a catalytic amount of lithium salt in ethanol water as a solvent. 3) Ring-closing: toluene is used as a solvent, a reduction product and diethyl carbonate are added to 100 °C, a sodium methoxide solution is added dropwise, and the product is obtained after completion of the dropwise addition and after-treatment and purification after completion of the normal pressure distillation to the temperature of 100 °C heat preservation. The lithium salt is introduced to participate in the reaction, sodium borohydride is selected as a solvent, sodium borohydride is completely dissolved, and the lithium salt can be free from the compound to improve the reaction activity, so that the use amount of sodium borohydride is reduced to 2 equivalent, and the production cost is remarkably reduced.
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(2021/11/10)

Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds
Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.
Pallesen, Jakob S.,Narayanan, Dilip,Tran, Kim T.,Solbak, Sara M. ?.,Marseglia, Giuseppe,S?rensen, Louis M. E.,H?j, Lars J.,Munafò, Federico,Carmona, Rosa M. C.,Garcia, Anthony D.,Desu, Haritha L.,Brambilla, Roberta,Johansen, Tommy N.,Popowicz, Grzegorz M.,Sattler, Michael,Gajhede, Michael,Bach, Anders
p. 4623 - 4661
(2021/05/07)

Live-Cell Protein Modification by Boronate-Assisted Hydroxamic Acid Catalysis
Selective methods for introducing protein post-translational modifications (PTMs) within living cells have proven valuable for interrogating their biological function. In contrast to enzymatic methods, abiotic catalysis should offer access to diverse and new-to-nature PTMs. Herein, we report the boronate-assisted hydroxamic acid (BAHA) catalyst system, which comprises a protein ligand, a hydroxamic acid Lewis base, and a diol moiety. In concert with a boronic acid-bearing acyl donor, our catalyst leverages a local molarity effect to promote acyl transfer to a target lysine residue. Our catalyst system employs micromolar reagent concentrations and affords minimal off-target protein reactivity. Critically, BAHA is resistant to glutathione, a metabolite which has hampered many efforts toward abiotic chemistry within living cells. To showcase this methodology, we installed a variety of acyl groups inE. colidihydrofolate reductase expressed within human cells. Our results further establish the well-known boronic acid-diol complexation as abona fidebio-orthogonal reaction with applications in chemical biology and in-cell catalysis.
Adamson, Christopher,Kajino, Hidetoshi,Kanai, Motomu,Kawashima, Shigehiro A.,Yamatsugu, Kenzo
supporting information
p. 14976 - 14980
(2021/09/29)

Preparation method of (S)-4-phenyl-2-oxazolidinone
The invention discloses a preparation method for synthesizing (S)-4-phenyl-2-oxazolidinone, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: reducing N-Boc-L-phenylglycine with a borane reagent to obtain N-Boc-L-phenylglycinol, and carrying out a ring closing reaction under the action of a catalyst to obtain (S)-4-phenyl-2-oxazolidinone. The product reacts with sulfur powder and ammonium sulfide or ammonium polysulfide to obtain (S)-4-phenyl oxazolidine-2-thioketone. The method avoids the use of cytotoxic reagents or solvents, has the advantages of accessible raw materials, simple operation and the like, conforms to green chemistry, and has potential industrial amplification prospects.
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(2021/03/18)

Preparation method of S-4-phenyl-2-oxazolidinone
The invention discloses a preparation method of S-4-phenyl-2-azolidinone. The preparation method comprises the following steps: reducing a compound 8 by potassium borohydride under acidic conditions to obtain a compound 9, and cyclizing the compound 9 and diethyl carbonate under alkaline conditions to obtain a compound 10, thereby obtaining (s)-4-phenyl-2-azolidinone. The raw materials used in the preparation method are easy to obtain, the reaction conditions are mild, the steps are simple, flammable and explosive reagents are not used, and the preparation method is suitable for large-scale industrial production and high in safety; the reaction yield is higher, and the cost is lower. Wide application prospects are realized.
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Paragraph 0021-0022

(2021/05/01)

Chiral separation materials based on derivatives of 6-amino-6-deoxyamylose
In order to develop new type of chiral separation materials, in this study, 6-amino-6-deoxyamylose was used as chiral starting material with which 10 derivatives were synthesized. The amino group in 6-amino-6-deoxyamylose was selectively acylated and then the hydroxyl groups were carbamoylated yielding amylose 6-amido-6-deoxy-2,3-bis(phenylcarbamate)s, which were employed as chiral selectors (CSs) for chiral stationary phases of high-performance liquid chromatography. The resulted 6-amido-6-deoxyamyloses and amylose 6-amido-6-deoxy-2,3-bis(phenylcarbamate)s were characterized by IR, 1H NMR, and elemental analysis. Enantioseparation evaluations indicated that most of the CSs demonstrated a moderate chiral recognition capability. The 6-nonphenyl (6-nonPh) CS of amylose 6-cyclohexylformamido-6-deoxy-2,3-bis(3,5-dimethylphenylcarbamate) showed the highest enantioselectivity towards the tested chiral analytes; the phenyl-heterogeneous (Ph-hetero) CS of amylose 6-(4-methylbenzamido)-6-deoxy-2,3-bis(3,5-dimethylphenylcarbamate) baseline separated the most chiral analytes; the phenyl-homogeneous (Ph-homo) CS of amylose 6-(3,5-dimethylbenzamido)-6-deoxy-2,3-bis(3,5-dimethylphenylcarbamate) also exhibited a good enantioseparation capability among the developed CSs. Regarding Ph-hetero CSs, the enantioselectivity depended on the combination of the substituent at 6-position and that at 2- and 3-positions; as for Ph-homo CSs, the enantioselectivity was related to the substituent at 2-, 3-, and 6-positions; with respect to 6-nonPh CSs, the retention factor of most analytes on the corresponding CSPs was lower than that on Ph-hetero and Ph-homo CSPs in the same mobile phases, indicating π–π interactions did occur during enantioseparation. Although the substituent at 6-position could not provide π–π interactions, the 6-nonPh CSs demonstrated an equivalent or even higher enantioselectivity compared with the Ph-homo and Ph-hetero CSs.
Gao, Ya-Ya,Zhang, Yu-Hang,Zhang, Shan,Chen, Wei,Bai, Zheng-Wu
supporting information
p. 899 - 914
(2021/10/07)

Efficient Access to Chiral 2-Oxazolidinones via Ni-Catalyzed Asymmetric Hydrogenation: Scope Study, Mechanistic Explanation, and Origin of Enantioselectivity
Cheap transition metal Ni-catalyzed asymmetric hydrogenation of 2-oxazolones was successfully developed, which provided an efficient synthetic strategy to prepare various chiral 2-oxazolidinones with 95%-99% yields and 97%->99% ee. The gram-scale hydrogenation could be proceeded well with >99% ee in the presence of low catalyst loading (up to 3350 TON). This Ni-catalyzed hydrogenation protocol demonstrated great synthetic utility, and the chiral 2-oxazolidinone product was easily converted to a variety of other important molecules in good yields and without loss of ee values, such as chiral dihydrothiophene-2(3H)-thione, amino alcohol, oxazoline ligand, and allenamide. Moreover, a series of deuterium labeling experiments, control experiments, and DFT calculations were conducted to illustrate a reasonable catalytic mechanism for this Ni-catalyzed asymmetric hydrogenation, which involved a tautomerization between the enamine and its isomer imine and then went through asymmetric 1,2-addition of Ni(II)-H to the preferred imine.
Dong, Xiu-Qin,Liu, Yuanhua,Wang, Heng,Wang, Minyan,Yang, Xuanliang,Yi, Zhiyuan,Yin, Congcong,Zhang, Xumu
p. 11153 - 11161
(2020/11/23)

Asymmetric catalysis with a chiral-at-osmium complex
The first example of a chiral osmium catalyst is reported in which the overall chirality originates exclusively from a stereogenic metal center (metal-centered chirality) with all coordinating ligands being achiral. The non-C2-symmetric chiral-at-metal complex contains two cyclometalated 7-methyl-1,7-phenanthrolinium heterocycles which can be described as two chelating pyridylidene remote N-heterocyclic carbene (rNHC) ligands. The octahedral coordination sphere is completed with one CO and one acetonitrile ligand. A monodentate chiral oxazoline ligand is used as a chiral auxiliary ligand to obtain enantiomerically pure chiral-at-osmium complexes (>99?:?1 e.r.). Finally, it is demonstrated that the developed chiral-at-osmium complex is suitable for ring-closing enantioselective C(sp3)-H aminations, including the first example of catalytic enantioselective cyclizations of azidoformates to chiral 2-oxazolidinones.
Wang, Guanghui,Zhou, Zijun,Shen, Xiang,Ivlev, Sergei,Meggers, Eric
supporting information
p. 7714 - 7717
(2020/07/27)

Synthesis of Chiral 5-Aryl-2-oxazolidinones via Halohydrin Dehalogenase-Catalyzed Enantio- and Regioselective Ring-Opening of Styrene Oxides
An efficient biocatalytic approach for enantio- and regioselective ring-opening of styrene oxides with cyanate was developed by using the halohydrin dehalogenase HheC from Agrobacterium radiobacter AD1, generating the corresponding chiral 5-aryl-2-oxazoli
Wan, Nanwei,Zhou, Xiaoying,Ma, Ran,Tian, Jiawei,Wang, Huihui,Cui, Baodong,Han, Wenyong,Chen, Yongzheng
p. 1201 - 1207
(2020/02/05)

Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin combining cinchona alkaloid moiety
Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated β-cyclodextrin (β-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than β-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of β-CD moiety, which lead to the different enantioseparation of β-CD-QN-based CSP and β-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding β-CD-based CSP for certain samples.
Zhu, Lunan,Zhu, Junchen,Sun, Xiaotong,Wu, Yaling,Wang, Huiying,Cheng, Lingping,Shen, Jiawei,Ke, Yanxiong
p. 1080 - 1090
(2020/05/25)

β-Amino Phosphine Mn Catalysts for 1,4-Transfer Hydrogenation of Chalcones and Allylic Alcohol Isomerization
Mn complexes with amino acid derived PN ligands were used in the catalytic transfer hydrogenation (TH) of ketone and chalcone substrates in 2-propanol with mild heating. Moreover, chalcones are reduced selectively to the saturated ketone at short times and can be fully converted to the alcohol when reactions are prolonged. The mechanism of chalcone reduction was briefly considered. Allylic alcohols are not reactive in 2-propanol, but quantitative isomerization occurs in toluene. Thus, we suspect that the allylic alcohols are dehydrogenated and the resulting ketone is formed through a direct 1,4-hydrogenation of the chalcone. Finally, several other related ligands that have been used in Mn-based TH reactions were explored to test the viability of ligand design in favoring chemoselectivity. The β-amino phosphine ligands proved most effective in this regard.
Vigneswaran, Vipulan,MacMillan, Samantha N.,Lacy, David C.
p. 4387 - 4391
(2019/11/14)

PROCESS FOR PREPARING OPTICALLY PURE (R)-4-N-PROPYL-DIHYDROFURAN-2(3H)-ONE
The present invention discloses a process for preparing optically pure (R)-4-n-propyl-dihydrofuran-2(3H)-one, belonging to the field of chemical synthesis. According to the process, optically pure (S)-3-n-pentanoyl-4-substituted oxazol-2-one is used as a starting material, and after alkylation, reduction, cyano hydrolysis, lactonization, the product optically pure (R)-4-n-propyl-dihydrofuran-2(3H)-one is given. The preparation process has the advantages of easy availability of raw materials, low price, high yield, high optical purity of product, simple reaction conditions and simple operations.
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Paragraph 0103-0104

(2019/12/10)

Regioselective Ring-Opening of Styrene Oxide Derivatives Using Halohydrin Dehalogenase for Synthesis of 4-Aryloxazolidinones
A biocatalytic approach towards a range of 4-aryloxazolidinones is developed using a halohydrin dehalogenase from Ilumatobacter coccineus (HheG) as biocatalyst. The method is based on the HheG-catalyzed α-position regioselective ring-opening of styrene oxide derivatives with cyanate as a nucleophile, producing the corresponding 4-aryloxazolidinones in moderate to good yields. Synthesis of enantiopure 4-aryloxazolidinones is also achievable using chiral epoxide materials. (Figure presented.).
Wan, Nanwei,Tian, Jiawei,Zhou, Xiaoying,Wang, Huihui,Cui, Baodong,Han, Wenyong,Chen, Yongzheng
p. 4651 - 4655
(2019/08/27)

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)

METHOD FOR PRODUCING OPTICALLY ACTIVE CYCLIC AMINE DERIVATIVE OR SALT THEREOF
PROBLEM TO BE SOLVED: To provide a novel method for producing an optically active imidazole derivative having strong analgesic action on neuropathic pain, fibromyalgia or the like. SOLUTION: The present invention provides a method for producing an optically active imidazole derivative or a salt thereof comprising the following three steps (where, A is dialkylamino or 4-alkylpiperazine-1-yl group-substituted piperidinyl or pyrrolidinyl group; R1 is phenyl group, benzyl group or isopropyl group; R2 is fluorine-substitutable methyl or ethyl group; R4 is C1-3 alkyl group or the like). SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT
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(2018/12/05)

Highly Stereoselective 2-Oxonia-Cope Rearrangement: A Platform Enabling At-Will Control of Regio-, Enantio-, and Diastereoselectivity in the Vinylogous Aldol Reactions of Aldehydes
A distinctly different approach for the vinylogous aldolation of aldehydes is described, which exploits 2-oxonia-Cope rearrangement reactions between two readily available partners, a set of rationally designed chiral homoallylic alcohol synthons and aldehydes, under simple conditions. In these processes, chirality transfer from the former to the latter is nearly perfect, giving rise to excellent enantio- and diastereoselectivity without the regioselectivity issue associated with traditional vinylogous aldol reactions.
Padarti, Akhil,Kim, Dongeun,Han, Hyunsoo
p. 756 - 759
(2018/02/10)

Synthesis of new C3 symmetric amino acid- and aminoalcohol-containing chiral stationary phases and application to HPLC enantioseparations
We recently reported a new C3-symmetric (R)-phenylglycinol N-1,3,5-benzenetricarboxylic acid-derived chiral high-performance liquid chromatography (HPLC) stationary phase (CSP 1) that demonstrated better results as compared to a previously described N-3,5-dintrobenzoyl (DNB) (R)-phenylglycinol-derived CSP. Over a decade ago, (S)-leucinol, (R)-phenylglycine, and (S)-leucine derivatives were used as the starting materials of 3,5-DNB-based Pirkle-type CSPs for chiral separation. In this study, three new C3-symmetric CSPs (CSP 2, 3, and 4) were prepared by combining the ideas and results mentioned above. Here we describe the synthetic procedures and applications of the new C3-symmetric CSPs (CSP 2–CSP 4).
Yu, Jeongjae,Armstrong, Daniel W.,Ryoo, Jae Jeong
p. 74 - 84
(2017/12/26)

Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase
A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.
Hellinghausen, Garrett,Lopez, Diego A.,Lee, Jauh T.,Wang, Yadi,Weatherly, Choyce A.,Portillo, Abiud E.,Berthod, Alain,Armstrong, Daniel W.
p. 1067 - 1078
(2018/08/01)

OXAZOLINE PSEUDODIMERS, PHARMACEUTICAL COMPOSITIONS AND THE USE THEREOF
The present disclosure is directed to oxazoline mono- and hetero-pseudodimer compounds, such as compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof: These compounds are useful for treating pain. The present disclosure also relates to pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula (I) or (II) or a pharmaceutically acceptable salt or solvate thereof
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Paragraph 0455

(2017/12/15)

Continuous Flow Synthesis of Carbonylated Heterocycles via Pd-Catalyzed Oxidative Carbonylation Using CO and O2 at Elevated Temperatures and Pressures
A continuous-flow Pd-catalyzed oxidative carbonylation protocol utilizing CO and O2 gas for the synthesis of carbonylated heterocycles is described. The optimization of temperature, pressure, CO/O2 ratio, catalyst loading, and reaction time resulted in process intensified conditions for this transformation. The optimized continuous flow conditions (120 °C, 20 bar pressure, 24 min residence time) were used to prepare a number of benzoxazolone, 2-benzoxazolidinone, and other biologically and synthetically important five- and six-membered carbonylated heterocycles in good overall yield and purity (14 examples). The continuous-flow process enables the safe and scalable oxidative carbonylation using CO/O2 under elevated pressures and temperatures.
Chen, Yuesu,Hone, Christopher A.,Gutmann, Bernhard,Kappe, C. Oliver
p. 1080 - 1087
(2017/07/26)

Catalytic Enantioselective Reaction of Allenylnitriles with Imines Using Chiral Bis(imidazoline)s Palladium(II) Pincer Complexes
The first highly enantioselective reaction of allenylnitriles with imines has been developed. Excellent yields and enantioselectivities were observed for the reaction with various imines using chiral Phebim-PdII complexes. This process offers a simple and efficient synthetic route for various functionalized α-vinylidene-β-aminonitriles and their derivatives.
Kondo, Masaru,Omori, Masashi,Hatanaka, Tsubasa,Funahashi, Yasuhiro,Nakamura, Shuichi
p. 8677 - 8680
(2017/07/17)

Chiral 2-carbonyl oxazoline synthesizing method
The invention discloses a chiral 2-carbonyl oxazoline synthesizing method. Chiral 2-carbonyl oxazoline is shown as a formula in the specification. The chiral 2-carbonyl oxazoline synthesizing method comprises the following steps: performing a backflow reaction with 142.2 mole percent zinc chloride serving as a catalyst, 22.3mmol of ethyl cyanoglyoxylate-2-oxime, 10.0g of D-phenylglycinol and 50mL of chlorobenzene serving as a solvent for 60 hours; performing column chromatography separation; eluting with petroleum ether or dichloromethane according to a volume ratio of 1:1; allowing a collected first component to volatilize naturally in order to obtain single crystal (R)-4-carbonyl oxazoline-2-ketone.
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Paragraph 0010

(2016/10/31)

Iron-Catalyzed Diastereoselective Synthesis of Unnatural Chiral Amino Acid Derivatives
An iron-catalyzed diastereoselective synthesis of unnatural chiral (S)-α-amino acids with γ-quaternary carbon centers has been developed. The protocol uses inexpensive iron salt as the catalyst, readily available 2-phthaloyl acrylamide and alkenes as the starting materials, and phenylsilane as the reductant, and the reactions were performed well in mixed solvent of 1,2-dichloroethane and ethylene glycol at room temperature. The method shows some advantages including simple and wide substrates, mild conditions, high diastereoselectivity, and easy workup procedures.
Zhang, Hao,Li, Haifang,Yang, Haijun,Fu, Hua
p. 3362 - 3365
(2016/07/26)

Computer-assisted design, synthesis, binding and cytotoxicity assessments of new 1-(4-(aryl(methyl)amino)butyl)-heterocyclic sigma 1 ligands
In this work we applied a blend of computational and synthetic techniques with the aim to design, synthesize, and characterize new σ1 receptor (σ1R) ligands. Starting from the structure of previously reported, high-affinity benzoxazolone-based σ1 ligands, the three-dimensional homology model of the σ1R was exploited for retrieving the molecular determinants to fulfill the optimal pharmacophore requirements. Accordingly, the benzoxazolone moiety was replaced by other heterocyclic scaffolds, the relevant conformational space in the σ1R binding cavity was explored, and the effect on σ1R binding affinity was ultimately assessed. Next, the compounds designed in silico were synthesized, and their affinity and selectivity toward σ1and σ2receptors were tested. Finally, a representative series of best σ1R binders were assayed for cytotoxic activity on the SH-SY5Y human neuroblastoma cell line. Specifically, the new 4-phenyloxazolidin-2-one derivatives 2b (i.e., (R)-2b and (S)-2b) emerged as potential leads for further development as σ1R agents, as they were found endowed with the highest σ1R affinity (Kiσ1 values in the range 0.95–9.3?nM), and showed minimal cytotoxic levels exhibited in the selected, cell-based test, in line with a σ1R agonist behavior.
Zampieri, Daniele,Vio, Luciano,Fermeglia, Maurizio,Pricl, Sabrina,Wünsch, Bernhard,Schepmann, Dirk,Romano, Maurizio,Mamolo, Maria Grazia,Laurini, Erik
p. 712 - 726
(2016/07/06)

(Enantio)selective Hydrogen Autotransfer: Ruthenium-Catalyzed Synthesis of Oxazolidin-2-ones from Urea and Diols
A novel strategy for the synthesis of oxazolidin-2-ones from vicinal diols and urea is described. In this heterocycle synthesis, two different C?O and C?N bonds are sequentially formed in a domino process consisting of nucleophilic substitution and alcohol amination. The use of readily available starting materials and the good atom economy render this process environmentally benign. While this transformation is already highly chemo- and regioselective, we also developed the first asymmetric version of this method using (R)-(+)-MeO-BIPHEP as the chiral ligand.
Pe?a-López, Miguel,Neumann, Helfried,Beller, Matthias
supporting information
p. 7826 - 7830
(2016/07/07)

New synthetic strategy for chiral 2-oxazolidinones derivatives via rhodium-catalyzed asymmetric hydrogenation
Asymmetric hydrogenation of 4-substituted cyclic enamido esters catalyzed by a rhodium-TangPhos complex provides an efficient method for the synthesis of chiral 4-substituted oxazolinones with excellent yields and good enantioselectivities. The products are valuable chiral building blocks and the applications as chiral auxiliaries and pharmaceuticals are well-known.
Wang, Qingli,Tan, Xuefeng,Zhu, Ziyue,Dong, Xiu-Qin,Zhang, Xumu
supporting information
p. 658 - 662
(2016/01/26)

Eluent tolerance and enantioseparation recovery of chiral packing materials based on chitosan bis(phenylcarbamate)-(n-octyl urea)s for high performance liquid chromatography
The goal of the present work was to study the influence of the swelling of chitosan derivatives on the enantioseparation and the separation performance recovery of chiral stationary phases (CSPs) based on these derivatives. Therefore, six chitosan bis(phenylcarbamate)-(n-octyl urea)s were synthesized, which were coated on macroporous 3-aminopropyl silica gel affording new CSPs. Most of the CSPs demonstrated strong enantioseparation capability for the tested chiral compounds. The swelling capacity of the chitosan bis(phenylcarbamate)-(n-octyl urea)s in ethyl acetate, acetone and tetrahydrofuran (THF) was evaluated. Among the chitosan derivatives, the chitosan bis(3,5-dichlorophenylcarbamate)-(n-octyl urea) polymer showed the highest swelling capacity in ethyl acetate and THF. The polymer-based CSPs could be utilized with pure ethyl acetate and a normal phase containing 70% THF, but was damaged by pure THF. On the other hand, the separation performance of the damaged CSP could be recovered after it was allowed to stand for a period of time. The observations are important for the development and application of polysaccharide derivative-based CSPs.
Wang, Jing,Huang, Shao-Hua,Chen, Wei,Bai, Zheng-Wu
supporting information

(2016/12/02)

A 4-substituted-2-oxazolidinone cyclization method
The invention discloses a cyclization method of 4-substituted-2-oxazolidone. The method is implemented through the following steps: (1) acylation: acylating chiral alkamine in a toluene solvent by adopting chloro-formate in the presence of potassium carbonate, so as to obtain chiral alkamine acylate; (2) cyclization: carrying out cyclization reaction through taking PEG-400 as a phase transfer catalyst, thereby obtaining 4-substituted-2-oxazolidone. Compared with the prior art, the cyclization method disclosed by the invention has the advantages that the adopted phase transfer catalyst is low in cost and is free of risk, reacting steps are reduced, the cost is reduced, and the conditions are mild, so that the method is suitable for industrial production.
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Paragraph 0019-0021

(2017/02/24)

Liquid Chromatographic Resolution of Racemic 2-Oxazolidinones and their Analogs on Seven Pirkle-Type Chiral Stationary Phases
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Yu, Jeong Jae,Hyun, Myung Ho,Armstrong, Daniel W.,Breitbach, Zachary S.,Ryoo, Jae Jeong
p. 723 - 726
(2015/07/20)

Asymmetric synthesis of 3,3,5,5-tetrasubstituted 1,2-dioxolanes: Total synthesis of epiplakinic acid F
The first enantioselective total synthesis of epiplakinic acid F (1) was achieved through a pivotal step involving a radical-mediated asymmetric peroxidation of vinylcyclopropanes with molecular oxygen to construct highly substituted 1,2-dioxolanes. Subsequent conversions of the chiral 1,2-dioxolanes led to total synthesis of epiplakinic acid F (1) and the confirmation of its absolute configuration. The enantiomer of epiplakinic acid F methyl ester (2) was also prepared. This journal is the Partner Organisations 2014.
Tian, Xiang-Yin,Han, Jian-Wei,Zhao, Qiong,Wong, Henry N. C.
supporting information
p. 3686 - 3700
(2014/06/09)

Catalytic fluoride triggers dehydrative oxazolidinone synthesis from CO2
Herein, catalytic fluoride (F-) is demonstrated to be a trigger for dehydrative immobilization of atmospheric pressure CO2, such that reaction of CO2 with β-amino alcohols derived from natural amino acids gives optically pure oxazolidinones in high yields. A synergistic combination of fluoride and organosilicon agents (e.g., Bu4NF + Ph3SiF or siloxanes) enhances the catalytic activity and functional group compatibility. This system lies at the interface between homogenous and heterogeneous catalysis, and may prove useful for the development of recoverable/reusable siloxane-based CO2 immobilization materials. This journal is
Takada, Yuki,Foo, Siong Wan,Yamazaki, Yusuke,Saito, Susumu
p. 50851 - 50857
(2015/02/19)

Binding mode and structure-activity relationships around direct inhibitors of the Nrf2-Keap1 complex
An X-ray crystal structure of Kelch-like ECH-associated protein (Keap1) co-crystallised with (1S,2R)-2-[(1S)-1-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl) methyl]-1,2,3,4-tetrahydroisoquinolin-2-carbonyl]cyclohexane-1-carboxylic acid (compound (S,R,S)-1 a) was obtained. This X-ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)-1 a, as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently. To dock or not to dock? Nrf2 has become an attractive neuroprotective target, as the Nrf2 pathway provides a natural cell defense mechanism against damage. Targeting its physiological negative modulator Keap1 with small molecules may allow Nrf2 to play its protective role. To this end, an X-ray structure of Keap1 co-crystallised with compound (S,R,S)-1 a was obtained, elucidating its binding mode, which in turn helped to drive the drug design process.
Jnoff, Eric,Albrecht, Claudia,Barker, John J.,Barker, Oliver,Beaumont, Edward,Bromidge, Steven,Brookfield, Frederick,Brooks, Mark,Bubert, Christian,Ceska, Tom,Corden, Vincent,Dawson, Graham,Duclos, Stephanie,Fryatt, Tara,Genicot, Christophe,Jigorel, Emilie,Kwong, Jason,Maghames, Rosemary,Mushi, Innocent,Pike, Richard,Sands, Zara A.,Smith, Myron A.,Stimson, Christopher C.,Courade, Jean-Philippe
supporting information
p. 699 - 705
(2014/05/06)

Total synthesis of the macrocyclic n -methyl enamides palmyrolide a and 2 s -sanctolide a
Full details of the total syntheses of the initially reported and revised structures of the neuroprotective agent palmyrolide A are reported. The key macrocyclization step was achieved using a sequential ring-closing metathesis/olefin isomerization reaction. Furthermore, the total synthesis of the related macrolide (2S)-sanctolide A is reported. The synthesis used key elements from the synthesis of palmyrolide A, including the RCM/olefin isomerization sequence. The synthetic work described herein serves to facilitate the assignment of stereochemistry of the natural product sanctolide A and demonstrates the utility of this approach for the synthesis of macrocyclic tertiary enamide natural products.
Wadsworth, Andrew D.,Furkert, Daniel P.,Brimble, Margaret A.
p. 11179 - 11193
(2015/01/08)

Amidation of esters with amino alcohols using organobase catalysis
A catalytic protocol for the base-mediated amidation of unactivated esters with amino alcohol derivatives is reported. Investigations into mechanistic aspects of the process indicate that the reaction involves an initial transesterification, followed by an intramolecular rearrangement. The reaction is highly general in nature and can be extended to include the synthesis of oxazolidinone systems through use of dimethyl carbonate.
Caldwell, Nicola,Campbell, Peter S.,Jamieson, Craig,Potjewyd, Frances,Simpson, Iain,Watson, Allan J. B.
p. 9347 - 9354
(2014/12/11)

SUBSTITUTED N-PENTANAMIDE COMPOUNDS, PREPARATION METHODS AND USES THEREOF
The present invention relates to a (2R, 3R)-3-(3-substituted phenyl)-2-methyl n-pentanamide compounds as shown in the formula I and the preparation method thereof, wherein, the substituents are as defined in the specification, the present invention further relates to a use of the above compounds for the preparation of tapentadol II or its pharmaceutically acceptable salt, and the intermediates involved in the preparation process.
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(2014/01/08)

Catalytic, enantioselective N-acylation of lactams and thiolactams using amidine-based catalysts
In contrast to alcohols and amines, racemic lactams and thiolactams cannot be resolved directly via enzymatic acylation or classical resolution. Asymmetric N-acylation promoted by amidine-based catalysts, particularly Cl-PIQ 2 and BTM 3, provides a convenient method for the kinetic resolution of these valuable compounds and often achieves excellent levels of enantioselectivity in this process. Density functional theory calculations indicate that the reaction occurs via N-acylation of the lactim tautomer and that cation-π interactions play a key role in the chiral recognition of lactam substrates.
Yang, Xing,Bumbu, Valentina D.,Liu, Peng,Li, Ximin,Jiang, Hui,Uffman, Eric W.,Guo, Lei,Zhang, Wei,Jiang, Xuntian,Houk,Birman, Vladimir B.
supporting information
p. 17605 - 17612
(2013/01/15)

Interaction of substrate and catalyst during the formation of oxazolidinones from 2-aminoalcohols and diethyl carbonate using recyclable 1,3-dichlorodistannoxanes
An efficient synthesis of oxazolidinone (OXZ) using 2-aminoalcohols (2AAs) and diethyl carbonate (DEC) as reagents in the presence of recyclable catalyst 1,3-dichloro-1,1,3,3-tetraalkyldistannoxane, [(RR′SnCl)2O] 2 (1) is reported. 0.5 mol% (with respect to 2AA) of 1 provides OXZ quantitatively within 1 h at 80 °C with turnover frequency (TOF) of 200 h-1. The observed TOF is much higher than the reported value (4 h-1) of the most convenient and commercially feasible K 2CO3 catalyst. Chiral 2AAs produce OXZs with 99% ee. Molar dependency of 1, DEC and 2AA is found to be 1:2:2. Molar conductivities (Ω-1 cm2 mol-1) in DMSO at 25 °C are 6.41 for 1a (R = R′ = Bu), 5.25 for 1b (R = Bu, R′ = Ph), 2.87 for 1c (R = Ph, R′ = Bu), and 2.21 for 1d (R = R′ = Ph) which reveal the mobility of bridged Cl in 1 during reaction. The study of a broad range of substrates and reaction parameters supports a reaction pathway that begins with initial attack by -OH of the pre-formed 2-ethylcarbamato aminoalcohol (2ECA) of 2AA on Snb of 1 displacing the bridged Cl. Change in the reaction rates resulted due to various alkyl and aryl substituents on Sn provides better understanding of the distannoxane catalysis, which has not been attempted before for the said reaction.
Pulla, Sharon,Unnikrishnan, Vineed,Ramidi, Punnamchandar,Sullivan, Shane Z.,Ghosh, Anindya,Dallas, Jerry L.,Munshi, Pradip
experimental part
p. 33 - 43
(2011/05/02)

Parallel kinetic resolution of D-labelled 2-aryl-propionic and butanoic acids using quasi-enantiomeric combinations of oxazolidin-2-ones
The parallel kinetic resolution of racemic 2-aryl-2-deuterio-propionic and butanoic acids using an equimolar combination of quasi-enantiomeric oxazolidin-2-ones is discussed. The levels of diastereoselectivity were high leading to enantiomerically pure D-
Coulbeck, Elliot,Dingjan, Marco,Eames, Jason
experimental part
p. 193 - 205
(2010/11/18)

Resolution of pentafluorophenyl active esters using (S)-4-phenyloxazolidin- 2-thione
A series of structurally related racemic pentafluorophenyl active esters were resolved using an equimolar amount of (S)-4- phenyloxazolidin-2-thione. The levels of diastereocontrol were found to be excellent (>86% de at -30% conversion).
Shaye, Najla Al,Broughton, Tom W.,Coulbeck, Elliot,Eames, Jason
scheme or table
p. 960 - 964
(2009/09/29)

Stereoselective synthesis of quaternary center bearing azetines and their β-amino acid derivatives
(Chemical Equation Presented) We describe here the use of a stable, four-membered azetine heterocycle for the preparation of highly substituted β-amino acid derivatives. Imidazolidinone chiral auxiliaries were found to eliminate a competitive reaction pathway that had been present under previously reported conditions for azetine synthesis. The ephedrine derived imidazolidin-2-one 21 was allowed to react as its chlorotitanium enolate with O-methyl or -benzyl oximes under optimized conditions to gain improved access to azetines at the gram scale. The azetines were further found to undergo alkylation with complete diastereocontrol, affording the creation of a quaternary center. Subsequent ring opening with benzoyl chloride and auxiliary cleavage provided the corresponding β2,2,3-amino carbonyl derivatives in good yields.
MacNevin, Christopher J.,Moore, Rhonda L.,Liotta, Dennis C.
p. 1264 - 1269
(2008/04/05)

Parallel kinetic resolution of active esters using designer oxazolidin-2-ones derived from phenylglycine
The parallel kinetic resolution of racemic pentafluorophenyl 2-phenylpropionate using an equimolar combination of quasi-enantiomeric oxazolidin-2-ones is discussed. The levels of diastereoselectivity were excellent (>90% de) leading to separable quasi-enantiomeric oxazolidin-2-one adducts in good yield. This methodology was subsequently used to resolve a series of 2-aryl propionic and butanoic acids.
Chavda, Sameer,Coulbeck, Elliot,Dingjan, Marco,Eames, Jason,Flinn, Anthony,Northen, Julian
p. 1536 - 1548
(2008/12/21)

PROCESS FOR THE PRODUCTION OF EZETIMIBE AND INTERMEDIATES USED IN THIS PROCES
This invention provides a novel, industrially easily realizable and economical process comprising only few steps, and built on new intermediates for the production of 1-(4-3(R)- [3(S)-(4-fluorophenyl)-3-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone (ezetimibe) according to the following reaction scheme: (I), (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X), (XI) wherein, the substances of the general Formulas II, IV, VI, VIII, IX, X and XI are new, Formula III is a non-isolated intermediate, Rl, R2 and R3 are represented by the compounds of Formulas Va-Vd, (Va), (Vb), (Vc), (Vd) and R4 is a silil, e.g. tert.buthyl-dimethyl-silil, tert-buthyl-diphenyl-silil group.
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Page/Page column 19

(2008/06/13)

Kinetic resolution of 2-oxazolidinones via catalytic, enantioselective N-acylation
Kinetic resolution of racemic 2-oxazolidinones via catalytic, enantioselective N-acylation has been achieved for the first time and with outstanding selectivities. Copyright
Birman, Vladimir B.,Jiang, Hui,Li, Ximin,Guo, Lei,Uffman, Eric W.
p. 6536 - 6537
(2007/10/03)

Strecker reactions of chiral N-acylhydrazones
Development of a method for addition of trimethylsilyl cyanide to chiral oxazolidinone-derived N-acylhydrazones is described. The diastereoselectivity was found to be highly dependent on the substituent of the oxazolidinone moiety; 4-phenyl-2-oxazolidinone achieved much higher stereocontrol than four other oxazolidinones screened. The reaction gives modest selectivity with aliphatic hydrazones and excellent selectivity with hydrazones prepared from aromatic aldehydes.
Ding, Hui,Friestad, Gregory K.
p. 185 - 199
(2008/02/02)

Remarkably efficient charcoal-promoted ring-closing carbonylations
An efficient, versatile and practical gram-scale preparation of oxazolidinone, imidazolidinone and dioxolanone is achieved. Georg Thieme Verlag Stuttgart.
Alouane, Nacira,Boutier, Audrey,Baron, Cyriella,Vrancken, Emmanuel,Mangeney, Pierre
p. 885 - 889
(2007/10/03)

Dirhodium tetracarboxylates derived from adamantylglycine as chiral catalysts for enantioselective C-H aminations
(Chemical Equation Presented) The dirhodium tetracarboxylate, Rh 2(S-TCPTAD)4, derived from adamantylglycine, is an effective chiral catalyst for both inter- and intramolecular C-H aminations.
Reddy, Ravisekhara P.,Davies, Huw M. L.
p. 5013 - 5016
(2007/10/03)

IMPROVED PROCESS FOR THE PREPARATION OF EZETIMIBE
The present invention relates to a cost effective and industrially advantageous process for the preparation of (3R,4S)-l-(4-Fluorophenyl)-3-[3(S)-3-(4-fluorophenyl)-3 - hydroxypropyl)]-4-(4-hydroxyρhenyl)-2-azetidinone, referred to here as Ezetimibe, it is represented as formula (1).
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Page/Page column 12

(2008/06/13)

Enantioselective acyl transfer catalysts and their use in kinetic resolution of alcohols and desymmetrization of meso-diols
Novel enantioselective acylation catalysts comprising chiral derivatives of DHIP and DHIQ, having the following representative general structures are disclosed: These new compounds are useful for resolving racemates or further enhancing the enantiomeric excess of an enantiomerically enriched composition and for desymmetrizing meso compounds.
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Page/Page column 20

(2008/06/13)

Chemically modified mutant serine hydrolases show improved catalytic activity and chiral selectivity
This invention provides novel chemically modified mutant serine hydrolases that catalyze a transamidation and/or a transpeptidation and/or a transesterification reaction. The modified serine hydrolases have one or more amino acid residues in a subsite replaced with a cysteine, wherein the cysteine is modified by replacing the thiol hydrogen in the cysteine with a substituent group providing a thiol side chain comprising a moiety selected from the group consisting of a polar aromatic substituent, an alkyl amino group with a positive charge, and a glycoside. In particularly preferred embodiments, the substitutents include an oxazolidinone, a C1 to C15 alkyl amino group with a positive charge, or a glycoside.
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(2008/06/13)