- Effects of the preparation method on the performance of the Cu/ZnO/Al 2O3 catalyst for the manufacture of l-phenylalaninol with high ee selectivity from l-phenylalanine methyl ester
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The effects of the preparation method on the properties of Cu/ZnO/Al 2O3 catalysts for l-phenylalanine methyl ester hydrogenation to l-phenylalaninol were investigated in detail, including the precipitation method and conditions (the aging time, calcination temperature and so on), with the help of ICP-OES, N2 and N2O adsorption, XRD, H2-TPR and TEM techniques. The results show that physicochemical properties of the catalysts are greatly affected by the preparation method and conditions. The uniform size distribution of CuO species can be obtained by fractional co-precipitation. The appropriate aging time is 2 h, and the catalyst aged for 2 h has the largest metallic copper surface area (SCu) and surface copper amount and the smallest CuO crystallites. The lower calcination temperature is favorable for increasing the surface area and metallic copper surface area of the catalyst. The spinel structure CuAl2O4 phase can form after calcination at 550 °C. The turnover frequency (TOF) values of l-phenylalaninol formed using different catalysts indicate the structurally sensitive character of the title reaction, and SCu is not the sole cause affecting the catalytic activities of the catalysts. B-TOF on the basis of the active sites (Cu0) in the boundary between CuO and ZnO or Al2O3 was proposed; the relationships of B-TOF with dCuO (particle size of CuO) and SCu were established. Using the Cu/ZnO/Al2O3 catalyst prepared by fractional co-precipitation with aging at 70 °C for 2 h and calcination at 450 °C for 4 h, 83.6% selectivity to l-phenylalaninol without racemization was achieved. This journal is the Partner Organisations 2014.
- Shi, Zhangping,Xiao, Xiuzhen,Mao, Dongsen,Lu, Guanzhong
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- Enantioselective Synthesis of β-Hydrazino Alcohols Using Alcohols and N-Boc-Hydrazine as Substrates
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An enantioselective approach for the synthesis of α-hydrazino aldehydes is described that utilizes alcohols and N-Boc hydrazine instead of the conventional combination of aldehydes with azodicarboxylates. This protocol is enabled by merging in situ aerobic dual oxidation with asymmetric organocatalysis. This reaction also exhibits a high tolerance for varieties of substituents on the alcohol component. This approach features excellent enantiocontrol, cheap starting materials, operational simplicity, and scalability. The corresponding chiral β-hydrazino alcohols were obtained by sequential reduction with excellent enantioselectivity (up to 98% ee).
- Cui, Zhihao,Du, Da-Ming
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- Preparation of L-phenylalaninol with high ee selectivity by catalytic hydrogenation of L-phenylalaninate over Cu/ZnO/Al2O3 catalyst
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The Cu/ZnO/Al2O3 catalyst for hydrogenation of l-phenylalaninate to l-phenylalaninol was prepared by a co-precipitation method, and characterized by XRD, low-temperature N2 adsorption, H 2-TPR, N2O chemisorption and ICP-AES. The results show that the physicochemical properties of the catalyst are greatly affected by the ZnO amount, and that the exposed copper surface area, dispersion of CuO and BET surface area of the Cu/ZnO/Al2O3 catalyst (Cu/Zn/Al = 1.0:0.3:1.0) reach the largest. The chemoselectivity of l-phenylalaninol is changed with ZnO amount in the Cu/ZnO/Al2O3 catalyst, and when Cu/Zn/Al = 1.0:0.3:1.0, the catalyst exhibits higher catalytic performance and chemoselectivity to l-phenylalaninol. Furthermore, the effect of temperature, pressure, reaction time and the molar ratio of catalyst to ester on the catalytic hydrogenation of l-phenylalaninate were investigated. When the catalytic hydrogenation of l-phenylalaninate was operated at 110 °C and 4 MPa of H2 for 5 h, the yield of l-phenylalaninol can reach 69.2 %, and its ee selectivity is 99.84 %.
- Gao, Chunyou,Xiao, Xiuzheng,Mao, Dongsen,Lu, Guanzhong
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- A highly effective and stable CuZn0.3MgxAlOy catalyst for the manufacture of chiral l-phenylalaninol: The role of Mg and its hydrotalcite-like precursor
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Highly effective CuZn0.3MgxAlOy (x = 0-0.2) catalysts for the synthesis of chiral l-phenylalaninol derived from Cu-rich hydrotalcite-like precursors were prepared by a co-precipitation method with Na2CO3 as the precipitant, and their physicochemical and catalytic properties were characterized. The results show that the presence of Mg2+ ions can promote the formation of hydrotalcite-like (htl) precursors, and the Mg2+ content would affect the phase purity of the prepared htl precursors. The BET surface area, exposed copper surface area and amount of acid sites of the samples decreased with the increase in the molar ratio of Mg2+/Al3+. Also, the dense layered htl precursors are beneficial to the atomically uniform distribution of the corresponding metal oxides in the prepared catalysts, promoting the stronger interaction between Cu0 and Al2O3 after the catalysts were reduced (SMSI effect). The activity of the CuZn0.3MgxAlOy catalysts is greatly dependent on not only the metallic copper surface area, but also the SMSI effect and the acidity of the catalysts. When Mg2+/Al3+ = 0.1 (mol), a phase-pure htl precursor could be obtained, and after calcination, the prepared CZA-0.1 catalyst exhibited very excellent catalytic performance for the hydrogenation of l-phenylalanine methyl ester to chiral l-phenylalaninol. After 5 h of reaction at 110 °C and 4 MPa H2, 100% conversion of l-phenylalanine methyl ester and 91.1% yield of l-phenylalaninol with an ee value of ～100% were achieved. After recycling 13 times, the l-phenylalaninol selectivity of the CZA-0.1 catalyst only decreased by 7.2%.
- Shi, Zhangping,Zhang, Shuangshuang,Xiao, Xiuzhen,Mao, Dongsen,Lu, Guanzhong
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- Chemical development on the chiral auxiliary (S)-4-(phenylmethyl)-2-oxazolidinone utilizing automated synthesis and DoE
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Enantiopure 4-substituted oxazolidinones are well-known chiral auxiliaries for asymmetric synthesis of carboxylic acid derivatives. The 4-(phenylmethyl)-substituted oxazolidinones derived from D- or L-phenylalanine are known to be particularly useful. We have conducted chemical development studies toward an efficient and scaleable "one-pot" process for production of (S)-4-(phenylmethyl)-2-oxazolidinone 2. The first step in the process employed a sodium borohydride reduction of phenylalanine mediated by an additive. The second step utilized triphosgene as a phosgene source to effect cyclization of the intermediate amino alcohol. Both chemical steps and workup procedures were screened and optimized utilizing statistical design of experiments (DoE) and parallel synthesis. The procedure was further characterized in an automated reactor system that provided heat flow measurements and modeled production at the plant scale. The efficiency of this process was compared to those of others previously reported on the basis of raw material cost, time requirements, safety, and hazardous waste generation.
- Vo, Lanchi,Ciula, James,Gooding, Owen W.
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- Construction and activity evaluation of novel benzodioxane derivatives as dual-target antifungal inhibitors
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Ergosterol exert the important function in maintaining the fluidity and osmotic pressure of fungal cells, and its key biosynthesis enzymes (Squalene epoxidase, SE; 14 α-demethylase, CYP51) displayed the obvious synergistic effects. Therefore, we expected to discover the novel antifungal compounds with dual-target (SE/CYP51) inhibitory activity. In the progress, we screened the different kinds of potent fragments based on the dual-target (CYP51, SE) features, and the method of fragment-based drug discovery (FBDD) was used to guide the construction of three different series of benzodioxane compounds. Subsequently, their chemical structures were synthesized and evaluated. These compounds displayed the obvious biological activity against the pathogenic fungal strains. Notably, target compounds 10a-2 and 22a-2 possessed the excellent broad-spectrum anti-fungal activity (MIC50, 0.125–2.0 μg/mL) and the activity against drug-resistant strains (MIC50, 0.5–2.0 μg/mL). Preliminary mechanism studies have confirmed that these compounds effectively inhibited the dual-target (SE/CYP51) activity, they could cause fungal rupture and death by blocking the bio-synthetic pathway of ergosterol. Further experiments discovered that compounds 10a-2 and 22a-2 also maintained a certain of anti-fungal effect in vivo. In summary, this study not only provided the new dual-target drug design strategy and method, but also discover the potential antifungal compounds.
- An, Yunfei,Fan, Haiyan,Han, Jun,Liu, Wenxia,Sun, Bin,Xie, Honglei
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- Preparation method of oxazolidinone compound
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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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Paragraph 0044; 0047-0048
(2021/11/10)
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- Direct Access to Primary Amines from Alkenes by Selective Metal-Free Hydroamination
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Direct and selective synthesis of primary amines from easily available precursors is attractive yet challenging. Herein, we report the rapid synthesis of primary amines from alkenes via metal-free regioselective hydroamination at room temperature. Ammonium carbonate was used as ammonia surrogate for the first time, allowing for efficient conversion of terminal and internal alkenes into linear, α-branched, and α-tertiary primary amines under mild conditions. This method provides a straightforward and powerful approach to a wide spectrum of advanced, highly functionalized primary amines which are of particular interest in pharmaceutical chemistry and other areas.
- Du, Yi-Dan,Chen, Bi-Hong,Shu, Wei
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supporting information
p. 9875 - 9880
(2021/03/29)
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- Nucleophilic RhI Catalyzed Selective Isomerization of Terminal Aziridines to Enamides
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The selective isomerization of various terminal N-Boc protected aziridines to enamides was realized using the highly reactive nucleophilic rhodium catalyst C with the Lewis acid LiNTf2 as co-catalyst under moderate conditions. The reaction proceeds smoothly with only 1 molpercent catalyst loading and excellent yields were achieved. An intermediate containing an enamide with a non-conjugated terminal C=C double bond was detected during the course of the reaction, which isomerizes to form the thermodynamically favored 2-amido styrene. Mechanistic insight is gained based on these observations.
- Tian, Yingying,Kunz, Doris
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p. 4272 - 4275
(2020/07/04)
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- Nickel-Catalyzed Asymmetric Hydrogenation of 2-Amidoacrylates
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Earth-abundant nickel, coordinated with a suitable chiral bisphosphine ligand, was found to be an efficient catalyst for the asymmetric hydrogenation of 2-amidoacrylates, affording the chiral α-amino acid esters in quantitative yields and excellent enantioselectivity (up to 96 % ee). The active catalyst component was studied by NMR and HRMS, which helped us to realize high catalytic efficiency on a gram scale with a low catalyst loading (S/C=2000). The hydrogenated products could be simply converted into chiral α-amino acids, β-amino alcohols, and their bioactive derivatives. Furthermore, the catalytic mechanism was investigated using deuterium-labeling experiments and computational calculations.
- Chen, Jianzhong,Gridnev, Ilya D.,Hu, Yawen,Li, Bowen,Zhang, Wanbin,Zhang, Zhenfeng
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p. 5371 - 5375
(2020/02/15)
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- Nascent-HBr-Catalyzed Removal of Orthogonal Protecting Groups in Aqueous Surfactants
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Organic reactions in the aqueous environment have recently emerged as a promising research area. The generation of nascent-HBr from the slow hydrolysis of the dispersed catalyst, benzyl bromide, with the interior water present in the hydrophobic core of the confined micellar medium in aqueous surfactant is described for the first time. The sustained-release nascent-HBr enabled the chemoselective cleavages of acid-sensitive orthogonal functionalities present in carbohydrates, amino alcohols, and hydroxylated acyclic compounds in good to excellent yields.
- Bera, Smritilekha,Gupta, Shilpi,Mondal, Dhananjoy
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- Carbon isotope labeling of carbamates by late-stage [11C], [13C] and [14C]carbon dioxide incorporation
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A general procedure for the late-stage [11C], [13C] and [14C]carbon isotope labeling of cyclic carbamates is reported. This protocol allows the incorporation of carbon dioxide, the primary source of carbon-14 and carbon-11 radioisotopes, in a direct, cost-effective and sustainable manner. A disconnection/reconnection strategy, involving ring opening/isotopic closure, was also implemented.
- Del Vecchio, Antonio,Talbot, Alex,Caillé, Fabien,Chevalier, Arnaud,Sallustrau, Antoine,Loreau, Olivier,Destro, Gianluca,Taran, Frédéric,Audisio, Davide
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supporting information
p. 11677 - 11680
(2020/10/19)
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- Selective hydrogenation of primary amides and cyclic di-peptides under Ru-catalysis
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A ruthenium(II)-catalyzed selective hydrogenation of challenging primary amides and cyclic di-peptides to their corresponding primary alcohols and amino alcohols, respectively, is reported. The hydrogenation reaction operates under mild and eco-benign conditions and can be scaled-up.
- Subaramanian, Murugan,Sivakumar, Ganesan,Babu, Jessin K.,Balaraman, Ekambaram
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supporting information
p. 12411 - 12414
(2020/10/30)
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- Development of an engineered thermostable amine dehydrogenase for the synthesis of structurally diverse chiral amines
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Amine dehydrogenases (AmDHs) are emerging as a class of attractive biocatalysts for synthesizing chiral amines via asymmetric reductive amination of ketones with inexpensive ammonia as an amino donor. However, the AmDHs developed to date exhibit limited substrate scope. Here, using directed evolution, we engineered a GkAmDH based on a thermostable phenylalanine dehydrogenase from Geobacillus kaustophilus. The newly developed AmDH is able to catalyze reductive amination of a diverse set of ketones and functionalized hydroxy ketones with ammonia or primary amines with up to >99% conversion, thus accessing structurally diverse chiral primary and secondary amines and chiral vicinal amino alcohols, with excellent enantioselectivity (up to >99% ee) and releasing water as the sole by-product.
- Chen, Fei-Fei,Chen, Qi,Liu, Lei,Wang, Dong-Hao,Wang, Zhi-Long,Xu, Jian-He,Zhang, Zhi-Jun,Zheng, Gao-Wei
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p. 2353 - 2358
(2020/05/13)
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- Catalytic Hydrogenation of N-protected α-Amino Acids Using Ruthenium Complexes with Monodentate Phosphine Ligands
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A ruthenium complex with a monodentate phosphine ligand was used to catalytically hydrogenate N-protected α-amino acids under essential retention of the configuration of their α-chiral centers. Among the ligands tested for this hydrogenation, which proceeds at a relatively low temperature, tris(para-fluorophenyl)phosphine exhibited the best performance. In comparison, electron-rich monodentate, bidentate, and tridentate phosphines were far less effective. The precatalyst Ru(OAc)2[(p-FC6H4)3P]2 was synthesized and isolated, and its structure was determined by a single-crystal X-ray diffraction analysis. N-protected α-amino acids with neutral alkyl side chains, including polar functional groups such as sulfides, indoles, ethers, phenols, pyrroles, and arenes, are compatible with the applied hydrogenation conditions, affording the corresponding optically active 2-substituted-2-(1H-pyrrol-1-yl)ethan-1-ol (2-amino ethanol) derivatives in moderate to high yield. (Figure presented.).
- Saito, Akari,Yoshioka, Shota,Naruto, Masayuki,Saito, Susumu
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supporting information
p. 424 - 429
(2019/11/28)
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- Discovery of a novel cathepsin inhibitor with dual autophagy-inducing and metastasis-inhibiting effects on breast cancer cells
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Drug resistance and cancer cells metastasis have been the leading causes of chemotherapy failure and cancer-associated death in breast cancer patients. In present, various active molecules either exhibiting novel mechanism of action such as inducing autophagy or inhibiting metastasis have been developed to address these problems. However, the compounds exhibiting such dual functions have rarely been described. Previous work in our group showed that TSA, as a synthetic analog of asperphenamate, induced autophagic cell death in breast cancer cells instead of apoptosis. Furthermore, the target enzyme of TSA was predicted to be cathepin L (Cat L) by natural product consensus pharmacophore strategy. Accumulated evidences have shown that cathepsins are closely associated with migration and invasion of breast cancer cells. It seemed likely that TSA-like molecules may possess the dual functions of inducing autophagy and inhibiting metastasis. Therefore, sixty optically active derivatives were firstly designed and synthesized by replacing the A-ring moiety of TSA with other substituted-phenyl sulfonyl groups. Further cathepsin inhibitory activity assay showed that (S, S) and (S, R) isomers displayed no activity against four kinds of cathepsins (L, S, K, B), while all derivatives tested were inactive toward K and B subtypes. Compound 6a with meta-bromo substituent displayed the greatest inhibitory activity, and its inhibitory capability against Cat L and S was 3.9 and 11.5-fold more potent than that of TSA, respectively. Molecular docking also exhibited that 6a formed more hydrogen bonds or π-π contacts with Cat L or S than TSA. In order to determine whether 6a could play dual roles, its anti-cancer mechanism was further investigated. On the one hand, MDC staining experiment and western blotting analysis validated that 6a can induce autophagy in MDA-MB-231 cells. On the other hand, its metastatic inhibitory ability was also confirmed by wound healing and transwell chamber experiment.
- Yuan, Lei,Liu, Jun,He, Wenhui,Bao, Youmei,Sheng, Lei,Zou, Chunyang,Hu, Baichun,Ge, Wentao,Liu, Yang,Wang, Jian,Lin, Bin,Li, Yanchun,Ma, Enlong
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p. 239 - 253
(2018/12/04)
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- New alkaloidal metabolites from cultures of entomopathogenic fungus Cordyceps takaomontana NBRC 101754
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Two new alkaloidal metabolites, cordytakaoamides A (1) and B (2), as well as, 2-[(2-hydroxyethyl) amino] benzoic acid (3) and 2E-decenamide (4), and three known compounds (5–7) were isolated from ethyl acetate and n-butanol soluble portions of the entomopathogenic fungus, Cordyceps takaomontana NBRC 101754. Compounds 3 and 4 were isolated here for first time from natural resources. The chemical structures were established depending upon spectroscopic techniques such as 1D, 2D NMR, and HRMS. The absolute configuration of 1 and 2 was elucidated via the total synthesis of 1 as well as the experimental circular dichroism. Compound 3 was confirmed by a signal crystal X-ray analysis.
- Hama, Maichi,Elshamy, Abdelsamed I.,Yoneyama, Tatsuro,Kasai, Yusuke,Yamamoto, Hirohumi,Tanigawa, Kana,Oshiro, Ayari,Noji, Masaaki,Ban, Sayaka,Imagawa, Hiroshi,Umeyama, Akemi
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- Catalytic Mechanism Study on the 1,2- and 1,4-Transfer Hydrogenation of Ketimines and β-Enamino Esters Catalyzed by Axially Chiral Biscarboline-Based Alcohols
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Axial N-O alcohols, which have two large carboline moieties connected to the axis were synthesized and used in catalytic enantioselective 1,2- and 1,4-transfer hydrogenations of total 26 ketimines and β-enamino esters. Excellent levels of enantioselectivity ranging from 91% to 99% were achieved by using catalyst (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. Interestingly, a mixture of (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide and (aR)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide was also able to provide high enantioselectivities up to 95% that is the same as that using pure (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. A plausible catalytic mechanism was suggested and total four kinds of transition states (TS) including almost 60 TS structures were investigated using density functional theory (DFT) with different basis sets such as 6-311G(2d,p). The predicted activation energy data are consistent with the experimental results. (Figure presented.).
- Dong, Mengxian,Wang, Jie,Wu, Shijie,Zhao, Yang,Ma, Yangyang,Xing, Yongfei,Cao, Fei,Li, Longfei,Li, Zhenqiu,Zhu, Huajie
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supporting information
p. 4602 - 4610
(2019/08/30)
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- Regioselective Fluorination of α-Hydroxy-β-aminophosphonates by Using PyFluor
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We report a simple protocol for the synthesis of α-fluoro-β-aminophosphonates by the regioselective fluorination of α-hydroxy-β-aminophosphonates under mild conditions. The fluorination reactions were mediated by the PyFluor reagent and occurred with the retention of configuration. The main products of this reaction were a series of α-fluoro-β-aminophosphonates, which can be used as precursors in the preparation of medicinally important compounds (e.g., dipeptide analogues).
- Ka?mierczak, Marcin,Kubicki, Maciej,Koroniak, Henryk
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p. 3844 - 3852
(2018/07/31)
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- Highly Efficient and Robust Enantioselective Liquid–Liquid Extraction of 1,2-Amino Alcohols utilizing VAPOL- and VANOL-based Phosphoric Acid Hosts
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The large-scale production of enantiopure compounds in a cost-effective and environmentally friendly manner remains one of the major challenges of modern-day chemistry. The resolution of racemates through enantioselective liquid–liquid extraction was developed as a suitable solution but has remained largely underused, owing to a lack of highly efficient and robust chiral hosts to mediate the process. This paucity of hosts can in part be attributed to a poor understanding of the underlying principles behind these processes hindering the design of more efficient selectors. A previously untested class of hosts, VAPOL and VANOL derived phosphoric acids, has been studied in depth for the efficient enantioselective liquid–liquid extraction of 1,2-amino alcohols. A systematic investigation of extraction parameters was conducted, revealing many key interactions and DFT calculations illustrate the binding modes for the 1:1 complexes that are involved in chiral recognition. The resulting, now-optimized, procedures are highly robust and easy to implement. They are also easily scalable, as demonstrated by U-tube experiments.
- Pinxterhuis, Erik B.,Gualtierotti, Jean-Baptiste,Wezenberg, Sander J.,de Vries, Johannes G.,Feringa, Ben L.
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p. 178 - 184
(2017/12/15)
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- Thiourea polyether bridged chiral molecular tweezer and preparation and application thereof
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The invention discloses a thiourea polyether bridged chiral molecular tweezer and a preparation and an application thereof. The thiourea polyether bridged chiral molecular tweezer takes a thiourea polyether chain as a linking group, and the ent-beyerane skeleton is taken as a chiral arm, and a structure is as shown in a formula (I) or a formula (II). The present invention provides the applicationof the thiourea polyether bridged chiral molecular tweezer for identifying a chiral molecular object, wherein the chiral molecular object is D/L-amino acid ester hydrochloride. The synthesized molecular tweezer has certain chiral recognition performance for D/L-amino-acid ester hydrochloride, and can be used for chiral recognition and separation of enantiomers.
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Paragraph 0037-0038; 0039-0040
(2019/01/08)
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- Synthesis of tubuphenylalanine and epi-tubuphenylalanine via regioselective aziridine ring opening with carbon nucleophiles followed by hydroboration-oxidation of 1,1-substituted amino alkenes
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An efficient synthesis of N-Boc-tubuphenylalanine benzyl ester (N-Boc-Tup-OBn, 1a) and N-Boc-epi-tubuphenylalanine benzyl ester (N-Boc-epi-Tup-OBn, 1b) is reported herein. Regioselective aziridine 4 ring opening with carbon nucleophiles followed by hydrob
- Reddy, Ramesh B.,Dudhe, Premansh,Chauhan, Priyanka,Sengupta, Sagnik,Chelvam, Venkatesh
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p. 6946 - 6953
(2018/10/24)
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- Asymmetric Sulfinylations of N-Methylephedrine-Modified Tri- or Tetraalkyl Zincates by Symmetric Diaryl Sulfoxides
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Diethylzinc was treated with 1 or 2 equiv. of AlkMgCl or PhMgBr (preferably) or with 1 equiv. of nBuLi (less efficiently) for forming species – plausibly zincates – which were sulfinylated by diaryl sulfoxides to give racemic alkyl aryl sulfoxides in yields reaching 100 %. Dialkylzinc reagents were also activated by treatments with 1 or 2 equiv. of an enantiomerically pure alkylmagnesium β-aminoalkoxide. This worked best when the alkoxide stemmed from a dialkylmagnesium reagent and an equimolar amount of N-methyl-(–)-ephedrine. This second activation mode allowed sulfinylations of what was originally the dialkylzinc reagent with diaryl sulfoxides. This generated alkyl aryl sulfoxides with enantiomeric ratios up to 93:7 in up to 100 % yield.
- Ruppenthal, Simon,Brückner, Reinhard
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supporting information
p. 2518 - 2530
(2018/06/11)
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- Development of C2-Symmetric Chiral Bifunctional Triamines: Synthesis and Application in Asymmetric Organocatalysis
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The synthesis and application of a newly designed C2-symmetric chiral bifunctional triamine family (C2-CBT) is reported. These enantiopure chiral triamine scaffolds can be accessed in multigram amounts from simple amino acids while avoiding chromatographic purification. As a proof of principle, C2-CBT has been studied in the aldol reaction of cyclic ketones with isatins, with the target tertiary alcohols being formed in a highly efficient manner. Catalyst recovery by simple extraction techniques and subsequent reuse has been performed.
- Ca?ellas, Santiago,Alonso, Pedro,Pericàs, Miquel à.
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supporting information
p. 4806 - 4810
(2018/08/24)
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- Highly efficient enantioselective liquid-liquid extraction of 1,2-amino-alcohols using SPINOL based phosphoric acid hosts
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Access to enantiopure compounds on large scale in an environmentally friendly and cost-efficient manner remains one of the greatest challenges in chemistry. Resolution of racemates using enantioselective liquid-liquid extraction has great potential to meet that challenge. However, a relatively feeble understanding of the chemical principles and physical properties behind this technique has hampered the development of hosts possessing sufficient resolving power for their application to large scale processes. Herein we present, employing the previously untested SPINOL based phosphoric acids host family, an in depths study of the parameters affecting the efficiency of the resolution of amino-alcohols in the optic of further understanding the core principles behind ELLE. We have systematically investigated the dependencies of the enantioselection by parameters such as the choice of solvent, the temperature, as well as the pH and bring to light many previously unsuspected and highly intriguing interactions. Furthermore, utilizing these new insights to our advantage, we developed novel, highly efficient, extraction and resolving protocols which provide remarkable levels of enantioselectivity. It was shown that the extraction is catalytic in host by demonstrating transport in a U-tube and finally it was demonstrated how the solvent dependency could be exploited in an unprecedented triphasic resolution system.
- Pinxterhuis, Erik B.,Gualtierotti, Jean-Baptiste,Heeres, Hero J.,De Vries, Johannes G.,Feringa, Ben L.
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p. 6409 - 6418
(2017/08/29)
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- Synthesis and stereochemical assignment of geraniol- and nerol-derived Cygerol enantiomers
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The enantiomers (up to 99% ee) of both geraniol- and nerol-derived 2-cyclohexyl-5,9-dimethyldeca-4,8-dienoic acid, the active ingredient of the wound healing medication Cygerol, were prepared via a low-temperature alkylation, basic hydrolysis, derivatization with (S)-4-benzyloxazolidin-2-one and chromatographic separation steps. The absolute configuration of stereocenters in the antipodes having an (E)- or (Z)-geometry of the internal double bond was determined based on characteristic 1H NMR signals of the corresponding (S)-4-benzyloxazolidin-2-one-derived imides and on conversion to the known diethyl (S)-2-cyclohexylsuccinate and (S)-2-cyclohexylbutane-1,4-diol with reported specific rotations.
- Sukhanova, Anna A.,Puchkin, Ilya A.,Vasil'ev, Andrei A.,Zlotin, Sergei G.
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supporting information
p. 1834 - 1841
(2017/11/20)
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- Synthesis and biological evaluation of N-(carbobenzyloxy)-L-phenylalanine and N-(carbobenzyloxy)-L-aspartic acid-β-benzyl ester derivatives as potent topoisomerase IIα inhibitors
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A new series of thirteen N-(carbobenzyloxy)-L-phenylalanine and N-(carbobenzyloxy)-L-aspartic acid-β-benzyl ester compounds were synthesized and evaluated for antiproliferative activity against four different human cancer cell lines: cervical cancer (HeLa
- Han, Xiaoyan,Zhong, Yifan,Zhou, Guan,Qi, Hui,Li, Shengbin,Ding, Qiang,Liu, Zhenming,Song, Yali,Qiao, Xiaoqiang
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p. 3116 - 3126
(2017/05/25)
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- Heterogeneous Catalytic Hydrogenation of Chiral Amino Acid Methyl Esters to Amino Alcohols with Retention of Configuration Over Mg-Modified Cu/ZnO/Al2O3 Catalyst
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Selective hydrogenation of amino acid methyl esters to chiral amino alcohols is an important and fascinating process. The CuZn0.3Mg0.1AlOx catalyst for the synthesis of chiral amino alcohols was prepared by the fractional
- Zhan, Bing,Zhang, Shuangshuang,Yu, Jun,Xiao, Xiuzheng,Guo, Xiaoming,Mao, Dongsen,Lu, Guanzhong
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p. 2160 - 2166
(2017/07/25)
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- Design, synthesis and biological evaluation of novel asperphenamate derivatives
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A series of novel asperphenamate derivatives were designed and synthesized, including series I (the A-phenyl group replaced with various aromatic heterocycles) and series II (the acyl group substituted by sulfonyl group). All compounds have been screened for their antiproliferative activity in vitro against MCF-7, HeLa, and BEL-7402 cell lines by the standard MTT method. Structure-activity relationship studies displayed the heterocycle type played an important role in activity. Six-membered ring derivatives displayed more potency than five-membered ring and the sulfonyl group in A-ring region made an important contribution to activity. Among all derivatives, tosyl derivative 8c exhibited the greatest potency in three human cancer cell lines. Especially in MCF-7 cells, the cellular potency of 8c was approximately 3.0-fold more potent than that of cisplatin. Firstly, the mechanism of cell death induced by 8c in MCF-7 cells was investigated. The results showed that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest. Further studies indicated that 8c might induce autophagic cell death in HeLa and BEL-7402 cell lines.
- Liu, Qingyin,Li, Wei,Sheng, Lei,Zou, Chunyang,Sun, Hongxin,Zhang, Chunfeng,Liu, Yang,Shi, Jiyue,Ma, Enlong,Yuan, Lei
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- Acylaminoimidazole derivative and use thereof
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The invention belongs to the technical field of medicines and relates to an acylaminoimidazole derivative shown in the general formula I and its stereisomer and pharmaceutical acceptable salt, hydrate, solvate or prodrug. In the formula I, substituents R, R1, Ar, M and X are defined in the specification. The invention also relates to a method for preparing the compound shown in the formula I, a medicinal composition containing the compound and a use of the compound and the medicinal composition in preparation of drugs for treating and/or preventing cancers and other skin proliferative diseases. An antifungal experiment proves that the compound has strong resistance to shallow and deep fungi and can be used for preparation of an antibacterial drug.
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Paragraph 0445; 0448; 0449
(2016/10/07)
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- The reductive cleavage of picolinic amides
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Treatment of picolinic amides with excess zinc in aqueous hydrochloric acid at room temperature affords the corresponding amines in good to excellent yields. The mild reaction conditions exhibit useful functional group tolerance and facilitate the application of the picolinic amide moiety as a protecting group which can be easily introduced and selectively removed.
- O'Donovan, Daniel H.,De Fusco, Claudia,Spring, David R.
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supporting information
p. 2962 - 2964
(2016/07/06)
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- Copper(II) complexes of pyridine-oxazoline (Pyox) ligands: Coordination chemistry, ligand stability, and catalysis
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The coordination chemistry of copper(II) complexes bearing pyridine-oxazoline ("Pyox") ligands has been studied, with an aim of investigating their catalytic ability. Interestingly, the stability of the coordinated ligands has been shown to be much less than previously assumed: hydrolysis of the ligands by fortuitous water gives rise to 2-pyridine carboxylate formation, which encapsulate the copper in a two-dimensional coordination polymer 3. The complexes [Cu(R-Pyox)(NCMe)2(ClO4)2] {R = benzyl (Bn) 2a, phenyl (Ph) 2b, isopropyl (iPr) 2c} have been prepared, of which the benzyl derivative has been analysed by CW EPR spectroscopy. The complex [Cu(Bn-Pyox)(NCMe)2(ClO4)2] and the afore-mentioned coordination polymer have been crystallographically characterised. The performance of complexes 2a-c in the asymmetric allylic oxidation of cyclohexene is described.
- Hallett, Andrew J.,O'Brien, Thomas M.,Carter, Emma,Kariuki, Benson M.,Murphy, Damien M.,Ward, Benjamin D.
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- Ligand, metal complex containing ligand, and reaction using metal complex containing ligand
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A hydrogen transfer reaction may be more efficiently promoted by using a metal complex represented by Formula (2): (wherein, R1 to R8 are the same or different, and each represents a hydrogen atom, a substituted or unsubstituted alkyl group or the like; or wherein; R1 and R2, R2 and R3, R3 and R4, R4 and R5, and R5 and R6 are respectively bonded to each other to form a bivalent hydrocarbon group; R9 are the same or different, and each represents an alkyl group or cycloalkyl group; M is ruthenium (Ru) or the like; X is a ligand; and n is 0, 1 or 2). More specifically, the metal complex enables a hydrogenation reaction of various substrates having a stable carbonyl group or the like to be advanced with a high yield under mild conditions.
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Page/Page column 46-50
(2016/10/31)
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- Amino alcohol-derived chiral ionic liquids: structural investigations toward chiral recognition
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From tentative beginnings, chiral ionic liquids have emerged into functionalized and tailor-made materials that provide novel input in classical asymmetric synthesis and separations. However, despite this broad application range the prediction of any chiral ionic liquids' performance is difficult. We present a systematic study toward the chiral recognition properties of novel ionic liquids with an amino alcohol sub-structure derived from the chiral pool precursors ephedrine, prolinol, and phenylalaninol. The influence of different ionic head groups and core structures on the diastereomeric interactions between racemic Mosher's acid carboxylate and enantiopure chiral ionic liquids was systematically investigated to provide insight into their recognition properties prior to application of these chiral ionic liquids in various fields.
- Vasiloiu, Maria,Cervenka, Isabella,Gaertner, Peter,Weil, Matthias,Schr?der, Christian,Bica, Katharina
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p. 1069 - 1082
(2015/10/19)
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- N-substituted benzenepropanamide or benzenepropenamide derivatives for use in the treatment of pain and inflammation
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Compounds for use in the treatment or prophylaxis of pain, including acute and chronic pain (e.g., nociceptive pain, neuropathic pain, headaches, migraine), represented by general formula (I) in which: the dotted line represents a single or a double bond; and R5 and R5′ are independently —H, —OH or —OR6, where R6 is a linear or branched C1-C4 alkyl; X is -0-, —CH2O—, —CH2CH2O—, —CH(CH3)CH2O— or —CH2CH(CH3)O—; Z is —CH2CH2O—, —CH(CH3)CH2O— or —CH2CH(CH3)O—; m is an integer of O or 1; and n is an integer of 0-50. The compounds of the invention are also effective for reducing inflammation and may be used alone or in combination with other analgesics.
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Page/Page column 8; 9
(2015/12/17)
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- Probing o-diphenylphosphanyl benzoate (o-DPPB)-directed C - C bond formation: Total synthesis of dictyostatin
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Herein, we report a robust total synthesis of dictyostatin. This polyketide natural product has attracted much attention because of its impressive antiproliferative activity against several human cancer-cell lines. We accomplished its synthesis in a highly convergent manner from three fragments of equal complexity, which were prepared on multigram scale. The southern and northwestern subunits were constructed through application of our o-DPPB-directed hydroformylation and allylic substitution methodology, respectively. These methods generated the C6 and C14 stereocenters of dictyostatin with good diastereoselectivities and simultaneously allowed further elaboration of the fragments by Wittig olefination and Sharpless asymmetric epoxidation, respectively. The compelling performance of the hydroformylation and allylic substitution with regard to practicability, selectivity, and scale underline their value for the construction of propionate motifs.
- Wünsch, Sebastian,Breit, Bernhard
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supporting information
p. 2358 - 2363
(2015/02/05)
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- PROCESS FOR THE PREPARATION OF COBICISTAT INTERMEDIATES
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The present invention relates to cobicistat intermediates, processes and further conversion to cobicistat with improved yield and quality.
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Page/Page column 9
(2014/05/07)
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- Adding the right (or left) twist to tris-chelate complexes-coordination chemistry of chiral oxazolylphenolates with M3+ ions (M = Al or lanthanide)
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A series of homoleptic tris-chelate complexes ML3 (M = Al or rare earth; L = chiral or achiral oxazolyl phenolate or -naphtholate) is reported. In all cases, complexes crystallize as mer-isomers and complete diastereoselectivity is observed on
- Aspinall, Helen C.,Bacsa, John,Beckingham, Oliver D.,Eden, Edward G. B.,Greeves, Nicholas,Hobbs, Matthew D.,Potjewyd, Frances,Schmidtmann, Marc,Thomas, Christopher D.
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supporting information
p. 1434 - 1442
(2014/01/06)
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- N-Substituted Benzenepropanamide and Benzenepropenamide For Use in the Prevention or the Treatment of Affective Disorders
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Compounds for use in the treatment or prophylaxis of an affective disorder, which compound is represented by formula I in which the dotted line represents a single or a double bond; and R5 and R5′ are independently —H, —OH or —OR6, where R6 is a linear or branched C1-C4 alkyl; X is —CH2O—; Z is —CH2OH2O—, —CH(CH3)CH2O— or —CH2CH(CH3)O—; m is 1; and n is an integer of 1-5; or a pharmaceutically acceptable salt, prodrug, metabolite, or hydrate thereof.
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Paragraph 0081-0084
(2014/09/30)
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- Bis(amidate)bis(amido) titanium complex: A regioselective intermolecular alkyne hydroamination catalyst
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An efficient and selective bis(amidate)bis(amido) titanium precatalyst for the anti-Markovnikov hydroamination of alkynes is reported. Hydroamination of terminal and internal alkynes with primary alkylamines, arylamines, and hydrazines is promoted by 5-10 mol % of Ti catalyst. Various functional groups are tolerated including esters, protected alcohols, and imines. The in situ generated complex shows comparable catalytic activity, demonstrating its synthetic versatility for benchtop application. Applications of this catalyst for the synthesis of amino alcohols and a one-pot procedure for indole synthesis are described. A mechanistic proposal that invokes turnover-limiting protonolysis is presented to rationalize the observed regioselectivities.
- Yim, Jacky C.-H.,Bexrud, Jason A.,Ayinla, Rashidat O.,Leitch, David C.,Schafer, Laurel L.
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p. 2015 - 2028
(2014/04/03)
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- ANTI-CANCER POLYKETIDE COMPOUNDS
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Provided herein, inter alia, are anticancer polyketides. The uses of the polyketides described herein include treatment of cancer, for example, through regulation of the spliceosome and detection of spliceosome inhibition.
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Paragraph 0155
(2013/10/21)
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- Chiral oxazoline substituted optically active poly(m-phenylene)s: Synthesis and coupling polymerizations of (S)-4-benzyl-2-(3,5-dihalidephenyl) oxazoline using transition metal catalysts
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Optically active poly(m-phenylene)s substituted with chiral oxazoline derivatives have been synthesized by the nickel-catalyzed Yamamoto coupling reaction of optically active (S)-4-benzyl-2-(3,5-dihalidephenyl)oxazoline derivatives (X = Br or I). The structures and chiroptical properties of the polymers were characterized by spectroscopic methods and thermal gravimetric analyses. The polymers showed higher absolute optical specific rotation values than their corresponding monomer, and showed a Cotton effect at transition region of conjugated main chain. The optical activities of the polymers should be attributed to the higher order structure such as helical conformations. Moreover, the helical conformation could be induced by addition of metal salts into polymer solutions. The polymers showed good thermal stabilities, which was attributable to the oxazoline side chains.
- Rattanatraicharoen, Poompat,Tanaka, Yoko,Shintaku, Keiko,Kawaguchi, Takuro,Yamabuki, Kazuhiro,Oishi, Tsutomu,Onimura, Kenjiro
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p. 1315 - 1322
(2013/04/10)
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- N- SUBSTITUTED BENZENEPROPANAMIDE AND BENZENEPROPENAMIDE FOR USE IN THE PREVENTION OR THE TREATMENT OF AFFECTIVE DISORDERS
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Compounds for use in the treatment or prophylaxis of an affective disorder, which compound is represented by formula I in which the dotted line represents a single or a double bond; and R5 and R5' are independently -H, -OH or -OR6, where R6 is a linear or branched C1-C4 alkyl; X is -CH2O-; Z is -CH2ΟΗ2O-,-CH(CH3)CH2O- or -CH2CH(CH3)O-; m is 1; and n is an integer of 1-5; or a pharmaceutically acceptable salt, prodrug, metabolite, or hydrate thereof.
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Page/Page column 23
(2013/04/10)
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- Ionic liquid crystals derived from amino acids
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Novel chiral amino acid derived ionic liquid crystals with amine and amide moieties as spacers between the imidazolium head group and the alkyl chain were synthesised. The key step in the synthesis utilised the relatively uncommon SO3 leaving group in a microwave-assisted reaction. The mesomorphic properties of the mesogens were determined by differential scanning calorimetry (DSC), polarising optical microscopy (POM) and X-ray diffraction. All liquid crystalline salts exhibit a smecticA mesophase geometry with strongly interdigitated bilayer structures. An increase of the steric bulk of the stereogenic centre hindered the formation of mesophases. In case of phenylalanine-derived derivatives a mesomorphic behaviour was observed for shorter alkyl chains as compared to other amino acid derivatives indicating an additional stabilising effect by the phenyl moiety. Ionic liquid crystals from amino acids: Novel chiral amino acid derived imidazolium salts with amine or amide units were prepared through the sulfamidate. Depending on the steric bulk of the R group, the chain lengths and the type of anion X, stable SmA phases were detected (see scheme; Bn=benzyl). Copyright
- Mansueto, Markus,Frey, Wolfgang,Laschat, Sabine
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supporting information
p. 16058 - 16065
(2014/04/03)
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- Two modes of asymmetric polymerization of phenylacetylenes having an L -amino alcohol residue and two hydroxy groups
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Four novel chiral phenylacetylenes having an L-amino alcohol residue and two hydroxymethyl groups were synthesized and polymerized by an achiral catalyst ((nbd)Rh+[η6-(C6H5)B -(C6H5)3]) or a chiral catalytic system ([Rh(nbd)Cl]2/(S)- or (R)-phenylethylamine ((S)- or (R)-PEA)). The two resulting polymers having an L-valinol or L-phenylalaninol residue showed Cotton effects at wavelengths around 430 nm. This observation indicated that they had an excess of one-handed helical backbones. Positive and negative Cotton effects were observed only for the polymers having an L-valinol residue produced by using (R)- and (S)-PEA as a cocatalyst, respectively, although the monomer had the same chirality. Even when the achiral catalyst was used, the two resulting polymers having an L-valinol or L-phenylalaninol residue showed Cotton effects despite the long distance between the chiral groups and the main chain. We have found the first example of a new type of chiral monomer, that is, a chiral phenylacetylene monomer having an L-amino alcohol residue and two hydroxy groups that was suitable for both modes of asymmetric polymerization, that is, the helix-sense-selective polymerization (HSSP) with the chiral catalytic system and the asymmetric-induced polymerization (AIP) with the achiral catalyst. The other two monomers having L-alaninol and L-tyrosinol were found to be unsuitable to neither HSSP nor AIP because of their polymers' low solubility.
- Jia, Hongge,Li, Jun,Zang, Yu,Aoki, Toshiki,Teraguchi, Masahiro,Kaneko, Takashi
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p. 5134 - 5143
(2013/01/15)
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- A convenient one-step synthesis of stable β-amino alcohol N-boranes from α-amino acids
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Novel, non-cyclic -amino alcohol N-boranes are isolated from the sodium borohydride-sulfuric acid assisted direct reduction of a series of -amino acids. The reduction takes place in one step under mild conditions and affords the products in good yields. Georg Thieme Verlag Stuttgart · New York.
- Pinaka, Afroditi,Vougioukalakis, Georgios C.,Dimotikali, Dimitra,Psyharis, Vassilis,Papadopoulos, Kyriakos
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experimental part
p. 1057 - 1062
(2012/05/21)
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- Microwave-enhanced solid-phase synthesis of N,N′-linked aliphatic oligoureas and related hybrids
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A practical and efficient microwave-assisted solid-phase method for the synthesis of N,N′-linked oligoureas and related amide/urea hybrid oligomers, featuring the use of succinimidyl (2-azido-2-substituted ethyl) carbamate monomers, is reported. The rate enhancement of urea formation under microwave irradiation combined with the mild conditions of the phosphine-based azide reduction makes this approach very effective for routine synthesis of oligoureas and possibly for library production.
- Douat-Casassus, Céline,Pulka, Karolina,Claudon, Paul,Guichard, Gilles
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supporting information; experimental part
p. 3130 - 3133
(2012/09/08)
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- Structure of FD-895 revealed through total synthesis
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The total synthesis of FD-895 was completed through a strategy that featured the use of a tandem esterification ring-closing metathesis (RCM) process to construct the 12-membered macrolide and a modified Stille coupling to append the side chain. These stu
- Villa, Reymundo,Mandel, Alexander L.,Jones, Brian D.,La Clair, James J.,Burkart, Michael D.
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supporting information
p. 5396 - 5399
(2013/01/15)
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- Preparation of chiral 1,2,4-triazolium salts as new NHC precatalysts
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The preparation of new chiral N,N′-disubstituted 1,2,4-triazolium based NHC salt precursors, Ia′ and Ib, from phenylhydrazine and l-phenylalanine is reported. The 1,3,4-trisubstituted triazolium salt Ia′ was obtained by a stepwise ring construction from l-phenylalanine via the corresponding imino ether and acetohydrazonamide, while a heterocyclic O-/N-heteroatom exchange strategy, based on a ring-opening/ring-closure of the oxadiazolium precursor, afforded the 1,4-disubstituted 1,2,4-triazolium salt Ib. The need for two different synthetic strategies is discussed.
- Strand, Ragnhild B.,Solvang, Tina,Sperger, Christian A.,Fiksdahl, Anne
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experimental part
p. 838 - 842
(2012/09/22)
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- An Efficient Synthesis of a Hydroxyethylamine (HEA) Isostere and Its α-Aminophosphonate and Phosphoramidate Derivatives as Potential Anti-HIV Agents
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HIV protease is a promising drug target for AIDS therapy, and several potent HIV-1 protease inhibitors have been reported to date. Although existing inhibitors exhibit high selectivity, they have also been associated with severe side effects and the possi
- Bhattacharya, Asish K.,Rana, Kalpeshkumar C.,Pannecouque, Christophe,DeClercq, Eric
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p. 1601 - 1611
(2012/10/29)
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- Diastereoselective synthesis of N,N-dibenzyl-protected aminoalkyl hydroxyethylamines: Key building blocks for hydroxyethylamine-based BACE1 inhibitor
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(Chemical Equation Presented) L-Amino acids were reduced with NaBH 4 followed by reacting with benzyl bromide to give N,N-dibenzyl-protected aminoalkyl ethanol 3, which in turn underwent a Swern oxidation, a Johnson-Corey-Chaykovsky reaction, and a nucleophilic reaction to afford N,N-dibenzyl-protected aminoalkyl hydroxyethylamine 6 with a diastereomer ratio 2.5-2.9:1 of (2R, 3S)-6:(2S, 3S)-6. Copyright Taylor & Francis Group, LLC.
- Wu, Jie,Gao, Shanyun,Liao, Guochao,Lin, Hansen,Nie, Aihua
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scheme or table
p. 2907 - 2916
(2012/07/28)
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