cas 7533-40-6, L(+)-Leucinol | Articles data

Articles about 7533-40-6Total 94 be found

Article title
Article abstract
Author
Journal number and time
Download

Palladium(0)-Catalyzed Enantioselective Intramolecular Arylation of Enantiotopic Secondary C?H Bonds
The enantioselective functionalization of nonactivated enantiotopic secondary C?H bonds is one of the greatest challenges in transition-metal-catalyzed C?H activation proceeding by an inner-sphere mechanism. Such reactions have remained elusive within the realm of Pd0 catalysis. Reported here is the unique reactivity profile of the IBiox ligand family in the Pd0-catalyzed intramolecular arylation of such nonactivated secondary C?H bonds. Chiral C2-symmetric IBiox ligands led to high enantioselectivities for a broad range of valuable indane products containing a tertiary stereocenter, as well as the arylation of secondary C?H bonds adjacent to amides. Depending on the amide substituents and upon control of reaction time, indanes containing labile tertiary stereocenters were also obtained with high enantioselectivities. Analysis of the steric maps of the IBiox ligands indicated that the level of enantioselectivity correlates with the difference between the two most occupied and the two less occupied space quadrants, and provided a blueprint for the design of even more efficient ligands.
Melot, Romain,Zuccarello, Marco,Cavalli, Diana,Niggli, Nadja,Devereux, Michael,Bürgi, Thomas,Baudoin, Olivier
supporting information
p. 7245 - 7250
(2021/02/12)

Enantio- and Diastereodivergent Sequential Catalysis Featuring Two Transition-Metal-Catalyzed Asymmetric Reactions
This study demonstrates the feasibility and inherent benefits of combining two distinct asymmetric transition-metal-catalyzed reactions in one pot. The reported transformation features a Pd-catalyzed asymmetric allylic alkylation and a Rh-catalyzed enantioselective 1,4-conjugate addition, effectively converting simple allyl enol carbonate precursors into enantioenriched cyclic ketones with two remote stereocenters. Despite the anticipated challenges associated with controlling stereoselectivity in such a complex system, the products are obtained in enantiomeric excesses ranging up to >99 % ee, exceeding those obtained from either of the individual asymmetric reactions. In addition, since the stereoselectivity of both steps is under catalyst control, this one-pot reaction is enantio- and diastereodivergent, enabling facile access to all stereoisomers from the same set of starting materials.
Abel-Snape, Xavier,Lautens, Mark,Masson-Makdissi, Jeanne,Prieto, Liher
supporting information
p. 16932 - 16936
(2021/07/02)

Application of proteasome inhibitor in inhibition of novel coronavirus
The invention provides application of a proteasome inhibitor in inhibition of a novel coronavirus or preparation of novel coronavirus inhibitors. The proteasome inhibitor has a structure represented by a formula (I) or isomers, pharmaceutically acceptable salts thereof and prodrugs thereof. According to the application, by applying the proteasome inhibitor to inhibition of the novel coronavirus, good inhibiting activity is obtained, and a novel treatment way of think is provided for diseases such as pneumonia caused by the novel coronavirus.
-
Paragraph 0130; 0140-0142; 0162; 0172-0174

(2021/06/22)

Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics
Malaria remains a worldwide threat, afflicting over 200 million people each year. The emergence of drug resistance against existing therapeutics threatens to destabilize global efforts aimed at controlling Plasmodium spp. parasites, which is expected to leave vast portions of humanity unprotected against the disease. To address this need, systematic testing of a fungal natural product extract library assembled through the University of Oklahoma Citizen Science Soil Collection Program has generated an initial set of bioactive extracts that exhibit potent antiplasmodial activity (EC50 25 μM, selectivity index > 250). The unique chemodiversity afforded by these fungal isolates serves to unlock new opportunities for translating peptaibols into a bioactive scaffold worthy of further development.
Lee, Jin Woo,Collins, Jennifer E.,Wendt, Karen L.,Chakrabarti, Debopam,Cichewicz, Robert H.
supporting information
p. 503 - 517
(2021/03/01)

Copper(I) Phosphinooxazoline Complexes: Impact of the Ligand Substitution and Steric Demand on the Electrochemical and Photophysical Properties
A series of seven homoleptic CuI complexes based on hetero-bidentate P^N ligands was synthesized and comprehensively characterized. In order to study structure–property relationships, the type, size, number and configuration of substituents at the phosphinooxazoline (phox) ligands were systematically varied. To this end, a combination of X-ray diffraction, NMR spectroscopy, steady-state absorption and emission spectroscopy, time-resolved emission spectroscopy, quenching experiments and cyclic voltammetry was used to assess the photophysical and electrochemical properties. Furthermore, time-dependent density functional theory calculations were applied to also analyze the excited state structures and characteristics. Surprisingly, a strong dependency on the chirality of the respective P^N ligand was found, whereas the specific kind and size of the different substituents has only a minor impact on the properties in solution. Most importantly, all complexes except C3 are photostable in solution and show fully reversible redox processes. Sacrificial reductants were applied to demonstrate a successful electron transfer upon light irradiation. These properties render this class of photosensitizers as potential candidates for solar energy conversion issues.
Frey, Wolfgang,Giereth, Robin,Karnahl, Michael,Klo?, Marvin,Mengele, Alexander K.,Steffen, Andreas,Tschierlei, Stefanie
p. 2675 - 2684
(2020/03/04)

Data mining of amine dehydrogenases for the synthesis of enantiopure amino alcohols
Chiral amino alcohols are essential building blocks for the pharmaceutical industry, and are widely present in natural and synthetic bioactive compounds. Amine dehydrogenases (AmDHs) can asymmetrically reduce prochiral ketones with low-cost ammonia to chiral amines and water as by-products, using NAD(P)H as a cofactor under mild conditions, but hydroxy ketones with formation of chiral hydroxy amines have rarely been investigated. In this study, six new bacterial AmDHs derived from amino acid dehydrogenases (AADHs) were identified by data mining, and five out of the six enzymes were able to efficiently reduce 1-hydroxybutan-2-one (1a) to (S)-2-aminobutan-1-ol ((S)-2a) with 19-99% conversions and 99% ee. The five AmDHs were purified and biochemically characterized for reductive amination activity towards substrate 1a with the optimal pH at 8.5 or 9.0 and the optimal temperature at 45 °C, 50 °C or 55 °C, and provided reductive amination of a broad range of prochiral α-hydroxy ketones, and even of a model β-hydroxy ketone leading to β-hydroxy amine with 99% ee. Our study expands the toolbox of AmDHs in the synthesis of chiral amino alcohols.
Guo, Jinggong,Li, Jun-Kuan,Ma, Jun-An,Miao, Yuchen,Qu, Ge,Sun, Zhoutong,Wang, Hongyue
p. 5945 - 5952
(2020/10/08)

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
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
supporting information
p. 4602 - 4610
(2019/08/30)

Designing chiral amido-oxazolines as new chelating ligands devoted to direct Cu-catalyzed oxidation of allylic C–H bonds in cyclic olefins
A new type of amido-oxazoline ligands was conveniently synthesized from inexpensive and commercially available materials in high yields and enantiomeric excesses. The corresponding chiral copper complexes with this class of ligands [C2 symmetric S,S-bis(amido-oxazoline-Cu(II) complex] were synthesized accordingly. The ORTEP diagram of ligand 6a and complex 6a-copper were compared and characterization of the complex confirmed the involvement of both dentate parts of the ligands, the oxygen and nitrogen atoms, in complexation with copper. The utilization of this amido-oxazoline ligands in the copper-catalyzed enantioselective esterification of allylic C–H bonds of cyclic olefins with tert-butyl-4-nitrobenzoperoxoate resulted in the highest activities, yields (up to 95%) and enantioselectivities (up to 96%) in the presence of HZSM-5 zeolite. These new findings highlight the protocol as one of the most attractive and useful methods for the oxidation of the asymmetric allylic C–H bond of cycloalkenes compared to other methodologies reported in the literature.
Samadi, Saadi,Jadidi, Khosrow,Samadi, Mojgan,Ashouri, Akram,Notash, Behrouz
p. 862 - 867
(2019/01/08)

Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases
Chiral vicinal amino alcohols are an important motif found in many biologically active molecules. In this study, biocatalytic reductive amination of α-hydroxy ketones with ammonia was investigated using engineered amine dehydrogenases (AmDHs) derived from the leucine amino acid dehydrogenase (AADH) from Lysinibacillus fusiformis. The AmDHs thus identified enabled the synthesis of (S)-configured vicinal amino alcohols from the corresponding α-hydroxy ketones in up to 99% conversions and >99% ee. One of the AmDH variants was used to prepare a key intermediate for the antituberculosis pharmaceutical ethambutol.
Chen, Fei-Fei,Cosgrove, Sebastian C.,Birmingham, William R.,Mangas-Sanchez, Juan,Citoler, Joan,Thompson, Matthew P.,Zheng, Gao-Wei,Xu, Jian-He,Turner, Nicholas J.
p. 11813 - 11818
(2019/12/02)

Chiral resolution method for preparation of high-purity mono-configuration leucine
The invention relates to a chiral resolution method for preparation of high-purity mono-configuration leucine. The method comprises the specific steps: (1) using (1R, 2R)-1,2-cyclohexanediamine as a precursor, and performing multistep derivation so as to prepare a catenane chiral resolution agent; (2) dissolving racemic leucine in a mixed solution of ethanol and water, mixing the solution with thechiral resolution agent and copper chloride which have the same molar amount as mono-configuration leucine, and precipitating a solid; (3) performing rotary evaporation under reduced pressure so as to remove ethanol in the mixed solution, performing extraction with ethyl acetate, and concentrating the filtrate so as to obtain optically pure dextro-leucine with an ee value of 98.0% or above; and (4) dissolving the precipitated solid in the step (3) in deionized water, performing extraction with ethyl acetate, and concentrating the filtrate so as to obtain optically pure L-leucine with an ee value of 99.0% or above. The method has the advantages that the synthesis method of the catenane chiral resolution agent is simple, and has a high yield of chiral resolution, the separated leucine has ahigh optical purity, and the method has easy large-scale chiral resolution.
-
Paragraph 0017; 0018

(2019/10/01)

A new family of 1,2,3-oxathiazolidine-2,2-dioxide phosphonate derivatives: Synthesis, characterization and anticancer evaluation
An efficient synthesis of a new series of organophosphorus compounds having a cyclic sulfamidates moiety is described. The cyclic sulfamidate precursors were prepared from α-amino acids after four steps (Reduction, N-Boc protection, cyclization and cleavage). The novel organophosphonates were synthesized within two steps starting from the cyclic sulfamidate (chloroacetylation following by phosphorylation via Arbuzov reaction). A particular compound 7-a (diethyl phosphonate {2-[(4S)-4-benzyl-1,2,3-oxathiazolidin-3-yl-2,2-dioxyde]-2-oxoethyl}) was essayed for their in vitro cytotoxic activities against a panel of four cell lines (Jurkat, K562, U266, and A431). For all of these cells, the synthesized compound showed low cytotoxicity, even at high concentration levels (4?mM).
K'tir, Hacène,Aouf, Zineb,Souk, Tan Otea,Zerrouki, Rachida,Berredjem, Malika,Aouf, Nour-Eddine
p. 555 - 559
(2017/05/01)

Heterogeneous Catalytic Hydrogenation of Chiral Amino Acid Methyl Esters to Amino Alcohols with Retention of Configuration Over Mg-Modified Cu/ZnO/Al2O3 Catalyst
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
p. 2160 - 2166
(2017/07/25)

Design, Synthesis, Fungicidal Activity, and Unexpected Docking Model of the First Chiral Boscalid Analogues Containing Oxazolines
Chirality greatly influences the biological and pharmacological properties of a pesticide and will contribute to unnecessary environmental loading and undesired ecological impact. No structure and activity relationship (SAR) of enantiopure succinate dehydrogenase inhibitors (SDHIs) was documented during the structure optimization of boscalids. On the basis of commercial SDHIs, oxazoline natural products, and versatile oxazoline ligands in organic synthesis, the first effort was devoted to explore the chiral SDHIs and the preliminary mechanism thereof. Fine-tuning furnished chiral nicotinamides 4ag as a more promising fungicidal candidate against Rhizoctonia solani, Botrytis cinerea, and Sclerotinia sclerotiorum, with EC50 values of 0.58, 0.42, and 2.10 mg/L, respectively. In vivo bioassay and molecular docking were investigated to explore the potential in practical application and plausible novelty in action mechanism, respectively. The unexpected molecular docking model showed the different chiral effects on the binding site with the amino acid residues. This chiral nicotinamide also featured easy synthesis and cost-efficacy. It will provide a powerful complement to the commercial SDHI fungicides with the introduction of chirality.
Li, Shengkun,Li, Dangdang,Xiao, Taifeng,Zhang, Shasha,Song, Zehua,Ma, Hongyu
p. 8927 - 8934
(2016/12/07)

Enantiodivergent Synthesis of (+)- and (?)-Pyrrolidine 197B: Synthesis of trans-2,5-Disubstituted Pyrrolidines by Intramolecular Hydroamination
A highly efficient, diastereoselective, iron(III)-catalyzed intramolecular hydroamination/cyclization reaction involving α-substituted amino alkenes is described. Thus, enantiopure trans-2,5-disubstituted pyrrolidines and trans-5-substituted proline derivatives were synthesized by means of a combination of enantiopure starting materials, easily available from l-α-amino acids, with sustainable metal catalysts such as iron(III) salts. The scope of this methodology is highlighted in an enantiodivergent approach to the synthesis of both (+)- and (?)-pyrrolidine 197B alkaloids from l-glutamic acid. In addition, a computational study was carried out to gain insight into the complete diastereoselectivity of the transformation.
Pérez, Sixto J.,Purino, Martín A.,Cruz, Daniel A.,López-Soria, Juan M.,Carballo, Rubén M.,Ramírez, Miguel A.,Fernández, Israel,Martín, Víctor S.,Padrón, Juan I.
supporting information
p. 15529 - 15535
(2016/10/13)

Discovery of (S)-4-isobutyloxazolidin-2-one as a novel leucyl-tRNA synthetase (LRS)-targeted mTORC1 inhibitor
A series of leucinol analogs were investigated as leucyl-tRNA synthetase-targeted mTORC1 inhibitors. Among them, compound 5, (S)-4-isobutyloxazolidin-2-one, showed the most potent inhibition on the mTORC1 pathway in a concentration-dependent manner. Compound 5 inhibited downstream phosphorylation of mTORC1 by blocking leucine-sensing ability of LRS, without affecting the catalytic activity of LRS. In addition, compound 5 exhibited cytotoxicity against rapamycin-resistant colon cancer cells, suggesting that LRS has the potential to serve as a novel therapeutic target.
Yoon, Suyoung,Kim, Jong Hyun,Yoon, Ina,Kim, Changhoon,Kim, Sung-Eun,Koh, Yura,Jeong, Seung Jae,Lee, Jiyoun,Kim, Sunghoon,Lee, Jeewoo
p. 3038 - 3041
(2016/06/13)

Two rearrangement pathways in the geminal acylation of 2-methoxyoxazolidines leading to substituted 1,4-oxazines
Lewis acid-mediated geminal acylation of 2-methoxyoxazolidines with five- or six-membered acyloins followed by heterocyclization afforded 1,4-oxazines fused to cyclopentenone or cyclohexenone rings. Overall yields ranged from 30 to 73%. The position of the carbonyl group in the products depended on whether or not water was present during the ringexpanding acyl migration step. The route lacking water during the acyl migration step was best conducted in one pot. The addition of water effected cleavage of a silyloxy group in the intermediate during the initial Mukaiyama aldol reaction prior to the acyl migration.
Moulins, Jonathan R.,Hughes, Jeremy A.,Doyle, Lauren E.,Cameron, T. Stanley,Burnell, D. Jean
supporting information
p. 1325 - 1332
(2015/03/04)

Metal-free one-pot synthesis of 2-substituted and 2,3-disubstituted morpholines from aziridines
The metal-free synthesis of 2-substituted and 2,3-disubstituted morpholines through a one-pot strategy is described. A simple and inexpensive ammonium persulfate salt enables the reaction of aziridines with halogenated alcohols to proceed via an SN2-type ring opening followed by cyclization of the resulting haloalkoxy amine.
Sun, Hongnan,Huang, Binbin,Lin, Run,Yang, Chao,Xia, Wujiong
supporting information
p. 524 - 529
(2015/06/08)

Modular, One-Pot, Sequential Aziridine Ring Opening-SNAr Strategy to 7-, 10-, and 11-Membered Benzo-Fused Sultams
The generation of common and stereochemically rich medium-sized benzo-fused sultams via complementary pairing of heretofore-unknown (o-fluoroaryl)sulfonyl aziridine building blocks with an array of amino alcohols/amines in a modular one-pot, sequential protocol using an aziridine ring opening and intramolecular nucleophilic aromatic substitution is reported. The strategy employs a variety of amino alcohols/amines and proceeds with 6 + 4/6 + 5 and 6 + 1 cycloetherification pathways in a highly chemo- and regioselective fashion to obtain skeletally and structurally diverse, polycyclic, 10- to 11- and 7-membered benzo-fused sultams for broad-scale screening.
Loh, Joanna K.,Asad, Naeem,Samarakoon, Thiwanka B.,Hanson, Paul R.
p. 9926 - 9941
(2015/11/03)

Catalytic hydrogenation of amino acids to amino alcohols with complete retention of configuration
Rh-MoOx/SiO2 is an effective heterogeneous catalyst for selective hydrogenation of amino acids to amino alcohols in a water solvent. MoOx modification of Rh drastically enhanced the activity and improved the selectivity and ee. Various amino alcohols were obtained in high yields (90-94%) with complete retention of configuration. This journal is the Partner Organisations 2014.
Tamura, Masazumi,Tamura, Riku,Takeda, Yasuyuki,Nakagawa, Yoshinao,Tomishige, Keiichi
p. 6656 - 6659
(2014/06/10)

Readily available ferrocenyl-phosphinite ligands for Ru(II)-catalyzed enantioselective transfer hydrogenation of ketones and fabrication of hybrid heterojunctions
A variety of phosphinite based on ferrocenyl moiety possessing central chirality have been screened as ligands for ruthenium(II)-catalyzed transfer hydrogenation of acetophenone derivatives using iso-PrOH as the hydrogen source to afford the corresponding product, (R) or (S)-1-phenylethanol derivatives with high conversions and good enantioselectivities. These complexes were also employed in the asymmetric reduction of different prochiral ketones (up to 85% ee). A comparison of the catalytic properties of amino alcohols and other analogs based on ferrocenyl backbone is also discussed briefly. The structures of these ligands and their corresponding complexes have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis. Furthermore, organic-inorganic hybrid heterojunctions were also fabricated by forming thin films of ruthenium(II) complexes on n-Si and evaporation of Au as front contact. Current-voltage (I-V) characteristics of the structures showed excellent rectification properties. Electrical parameters including ideality factor, barrier height and series resistance were determined using I-V and capacitance-voltage (C-V) data. Finally, photoelectrical properties of the structures were examined by means of a solar simulator with AM1.5 global filter.
Ak, Bünyamin,Aydemir, Murat,Ocak, Yusuf Selim,Durap, Feyyaz,Kayan, Cezmi,Baysal, Akin,Temel, Hamdi
p. 244 - 253
(2013/12/04)

New chiral 4-substituted 2-cyanoethyl-oxazolines: Synthesis and assessment of some biological activities
This paper describes the synthesis of new enantiomerically pure 2-cyanoethyl-oxazolines in one step starting from a wide range of amino alcohols and 4-ethoxy-4-iminobutanenitrile with high to good yields (73-96%) via an appropriate procedure which can be used for a selective synthesis of mono-oxazolines. A simple operation as well as a practical separation is additional eco-friendly attributes of this method. All the synthesized compounds were identified and characterized with their physicochemical features and their spectral data (1H NMR, 13C NMR and TOFMS ES+). Among the prepared mono-oxazolines, the mono-oxazoline (3a) [3-[(4S)-4-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile] was tested to detect some biological activities. This compound was studied in vitro given the various types of pharmacological properties characterizing these compounds such as antioxidant, antimicrobial and analgesic activities. The antioxidant activity and mechanism of (3a) were identified using various in vitro antioxidant assays including 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and superoxide anion radicals (O2-) scavenging activity. In addition, compared to Quercetin, the tested synthetic product reveals a relatively-strong antiradical activity towards the DPPH (activity percentage of 81.22%) free radicals and significantly decreased the reactive oxygen species such as (O2 -) formation evaluated by the non-enzymatic (nitroblue tetrazolium/riboflavine) and the enzymatic (xanthine/xanthine oxidase) systems. Related activity values were, respectively, 66% and 60.30%. The oxazoline (3a) showed a high ability to reduce the O2- generation and proved to be a very potent radical scavenger. On the other hand, the analgesic property of the 3[(4S)-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile (3a) was demonstrated. The subcutaneous administration of (3a) produced a significant reduction in the number of abdominal constrictions amounting to 73.81% in the acetic acid writhing test in mice. In addition to these advances, the oxazoline (3a) has been investigated as an antimicrobial agent. Our results showed that this molecule exhibited various levels of antibacterial effect against all the tested bacterial strains.
Hassani, Rym,Kacem, Yakdhane,Ben Mansour, Hedi,Ben Ammar, Hamed,Ben Hassine, Béchir
p. 41 - 48
(2014/05/20)

Tetrahydroquinoline-derived macrocyclic toolbox: The discovery of antiangiogenesis agents in zebrafish assay
A novel approach to incorporate the macrocyclic rings onto the privileged substructure, i.e., tetrahydroquinoline scaffold, is developed. The presence of an amino acid-derived moiety in the macrocyclic skeleton provides an opportunity to modulate the nature of the chiral side chain. Further, evaluation in a zebrafish screen identified three active small molecules (2.5b, 3.2d, and 4.2) as antiangiogenesis agents at 2.5 μM.
Reddy Guduru, Shiva Krishna,Chamakuri, Srinivas,Chandrasekar, Gayathri,Kitambi, Satish Srinivas,Arya, Prabhat
supporting information
p. 666 - 670
(2013/07/26)

Screening of C2-symmetric chiral phosphinites as ligands for ruthenium(II)-catalyzed asymmetric transfer hydrogenation of prochiral aromatic ketones
Metal-catalyzed transfer hydrogenation processes provide a widely-used alternative to direct hydrogenation processes of ketones. As part of an ongoing program, we report enantioselective C2-symmetric bis(phosphinite)- ruthenium(II) catalytic systems for the transfer hydrogenation of prochiral aromatic ketones. The new catalytic systems can readily be formed under in situ conditions from C2-symmetric chiral bis(phosphinite) ligands and [Ru(η6-p-cymene)(μ-Cl)Cl]2 in transfer hydrogenation reaction media. These chiral ruthenium catalytic systems serve as catalyst precursors for the asymmetric transfer hydrogenation of acetophenone derivatives in iso-PrOH and giving the corresponding optical active secondary alcohols up to 94% ee.
Elma, Duygu,Durap, Feyyaz,Aydemir, Murat,Baysal, Akin,Meric, Nermin,Ak, Bünyamin,Turgut, Ylmaz,Gümgüm, Bahattin
p. 46 - 52
(2013/08/25)

Tunable ferrocenyl-phosphinite ligands for the ruthenium(II)-catalyzed asymmetric transfer hydrogenation of ketones
We report here new examples of enantiomerically pure monodendate phosphinite ligands containing both a ferrocene moiety and NH bridging moiety adjacent to the stereocenter, as well as their ruthenium(II) dichloro complexes. The phosphinites based on ferrocenyl moiety possessing stereogenic center have been screened as ligands for ruthenium(II)-catalyzed transfer hydrogenation of aromatic ketones to give corresponding secondary alcohols using iso-PrOH as the hydrogen source in the presence of NaOH. Up to 99% conversion with 97% ee was obtained in the transfer hydrogenation of acetophenone derivatives. Furthermore, the catalytic properties of these catalysts based on ferrocenyl-phosphinite backbone are also discussed briefly. The structures of these ligand and their corresponding complexes have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis.
I?ik, U?ur,Aydemir, Murat,Meri?, Nermin,Durap, Feyyaz,Kayan, Cezmi,Temel, Hamdi,Baysal, Akin
p. 225 - 233
(2013/10/08)

Green asymmetric synthesis: β-amino alcohol-catalyzed direct asymmetric aldol reactions in aqueous micelles
The ability of chiral β-amino alcohols to catalyze the direct asymmetric aldol reaction was evaluated for the first time in aqueous micellar media. A family of cheap and easily accessible β-amino alcohols, obtained in one step from naturally occurring amino acids, was shown to successfully catalyze the asymmetric aldol reaction between a series of ketones and aromatic aldehydes. These aldol reactions furnished the corresponding β-hydroxy ketones with up to 93% isolated yield and 89% ee. (S)-2-phenylglycinol and Triton X-100 proved to be the best organocatalyst and surfactant, respectively. Copyright
Pinaka, Afroditi,Vougioukalakis, Georgios C.,Dimotikali, Dimitra,Yannakopoulou, Elina,Chankvetadze, Bezhan,Papadopoulos, Kyriakos
p. 119 - 125
(2013/08/24)

Building a macrocyclic toolbox from C-linked carbohydrates identifies antiangiogenesis agents from zebrafish assay
We report the synthesis of four different types of macrocyclic-derived glycohybrids from carbohydrates that have an amino acid moiety in the large-ring skeleton. These macrocyclic glycohybrids were obtained from α-C-1H- and β-C-1H-linked carbohydrates. In one series, we utilized ring-closing metathesis as the "stitching technology" to obtain two different macrocycles, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The click approach was the key reaction in our second series to obtain two other macrocyclic compounds, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The evaluation of this toolbox resulted in the identification of two unique compounds as antiangiogenesis agents in an embryonic zebrafish assay. Interestingly, in both cases, the macrocyclic compounds that have a cis relationship (i.e., axial-axial orientation) between C-1H and C-5H showed activity and their other diastereomers (i.e., equatorial-axial C-1H and C-5 H) with a trans relationship did not show any effect. The synthesis of four different types of macrocyclic glycohybrids that contain an amino acid moiety in the large-ring skeleton is reported. Ring-closing metathesis and click chemistry approaches were utilized to obtain two different series of macrocycles. The evaluation of this toolbox resulted in the identification of two unique compounds as antiangiogenesis agents in an embryonic zebrafish assay. Copyright
Jogula, Srinivas,Dasari, Bhanudas,Khatravath, Mahender,Chandrasekar, Gayathri,Kitambi, Satish Srinivas,Arya, Prabhat
supporting information
p. 5036 - 5040
(2013/11/06)

Coordinating chiral ionic liquids
A practical synthesis of novel coordinating chiral ionic liquids with an amino alcohol structural motif was developed starting from commercially available amino alcohols. These basic chiral ionic liquids could be successfully applied as catalysts in the asymmetric alkylation of aldehydes and gave high enantioselectivities of up to 91% ee.
Vasiloiu, Maria,Leder, Sonja,Gaertner, Peter,Mereiter, Kurt,Bica, Katharina
p. 8092 - 8102
(2013/12/04)

Diastereoselective synthesis of N,N-dibenzyl-protected aminoalkyl hydroxyethylamines: Key building blocks for hydroxyethylamine-based BACE1 inhibitor
(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
scheme or table
p. 2907 - 2916
(2012/07/28)

Catalytic asymmetric [4+2] annulation initiated by an aza-rauhut-currier reaction: Facile entry to highly functionalized tetrahydropyridines
Under control: The first example of chiral amino phosphine catalysts for the title reaction between vinyl ketones and N-sulfonyl-1-aza-1,3-dienes has been developed. Under ambient conditions, this protocol provides straightforward access to densely functionalized, enantioenriched tetrahydropyridines with high levels of sterecontrol in good to excellent yields. Copyright
Shi, Zugui,Yu, Peiyuan,Loh, Teck-Peng,Zhong, Guofu
supporting information; scheme or table
p. 7825 - 7829
(2012/09/08)

Synthesis of imidacloprid derivatives with a chiral alkylated imidazolidine ring and evaluation of their insecticidal activity and affinity to the nicotinic acetylcholine receptor
A series of imidacloprid (IMI) derivatives with an alkylated imidazolidine ring were asymmetrically synthesized to evaluate their insecticidal activity against adult female housefly, Musca domestica, and affinity to the nicotinic acetylcholine receptor of the flies. The bulkier the alkyl group, the lower was the receptor affinity, but the derivatives methylated and ethylated at the R-5-position of the imidazolidine ring were equipotent to the unsubstituted compound. Quantitative structure-activity relationship (QSAR) analysis of the receptor affinity demonstrated that the introduction of a substituent into the imidazolidine ring was fundamentally disadvantageous, but the introduction of a substituent at the R-5-position was permissible in the case of its small size. The binding model of the synthesized derivatives with the receptor supported the QSAR analysis, indicating the existence of space for a short alkyl group around the R-5-position in the ligand-binding site. In addition, positive correlation was observed between the insecticidal activity and receptor affinity, suggesting that the receptor affinity was the primary factor in influencing the insecticidal activity even if the imidazolidine ring was modified.
Nishiwaki, Hisashi,Kuriyama, Mituhiro,Nagaoka, Hikaru,Kato, Akira,Yamauchi, Satoshi,Shuto, Yoshihiro,Akamatsu, Miki
p. 6305 - 6312,8
(2012/12/11)

Synthesis of selenium-linked neoglycoconjugates and pseudodisaccharides
The introduction of organoselenium moieties within the structure of carbohydrates has received attention recently. Herein, we report on the synthesis of selenium-containing neoglycoconjugates and pseudodisaccharides by the reaction of nucleophilic selenium species, generated from sugar diselenides, with chiral N-Boc aziridines and sugar tosylates. The reaction proceeds with moderate to good yields for various substrates. The introduction of organoselenium moieties within the framework of various sugars, with increased levels of complexity, thus allowing the synthesis of disaccharide and glycoconjugate mimetics.
Affeldt, Ricardo F.,Baldassari, Lucas L.,Luedtke, Diogo S.,Braga, Hugo C.
p. 10470 - 10475,6
(2012/12/12)

A convenient one-step synthesis of stable β-amino alcohol N-boranes from α-amino acids
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
experimental part
p. 1057 - 1062
(2012/05/21)

Synthesis and SAR study of novel peptide aldehydes as inhibitors of 20S proteasome
Based on the analysis of the crystal structure of MG101 (1) and 20S proteasomes, a new series of peptide aldehyde derivatives were designed and synthesized. Their ability to inhibit 20S proteasome was assayed. Among them, Cbz-Glu(OtBu)-Phe-Leucinal (3c), Cbz-Glu(OtBu)-Leu-Leucinal (3d), and Boc-Ser(OBzl)-Leu-Leucinal (3o) exhibited the most activity, which represented an order of magnitude enhancement compared with MG132 (2). The covalent docking protocol was used to explore the binding mode. The structure-activity relationship of the peptide aldehyde inhibitors is discussed.
Ma, Yuheng,Xu, Bo,Fang, Yuan,Yang, Zhenjun,Cui, Jingrong,Zhang, Liangren,Zhang, Lihe
experimental part
p. 7551 - 7564
(2011/11/14)

Asymmetric synthesis of β-adrenergic blockers through multistep one-pot transformations involving in situ chiral organocatalyst formation
Two birds one stone: A new atom-economical one-pot approach to enantioselective chiral drug synthesis, involving in situ multistep organocatalyst formation and the application of the reaction for multistep sequential synthesis of β-adrenergic blockers is disclosed (see scheme).
Wei, Shengwei,Messerer, Regina,Tsogoeva, Svetlana B.
supporting information; experimental part
p. 14380 - 14384
(2012/02/01)

One-pot and microwave-assisted synthesis of N-sulfonylaziridines
A novel and efficient microwave-assisted one-step reaction was developed to synthesize chiral N-sulfonylaziridines by the reaction of different chiral amino alcohols and sulfonic chlorides. The newly developed microwave synthetic method has the advantage of reducing the reaction time from 24 to 0.5 h with improved yields (84-93%) and minimizing by-products.
Xu, Hao,Tian, Hua,Zheng, Liangyu,Liu, Qingwen,Wang, Li,Zhang, Suoqin
body text
p. 2873 - 2875
(2011/06/21)

The first synthesis of β-amino phosphonates using cyclic sulfamidates
Cyclic sulfamidates (prepared from α-amino acids and β-amino alcohols) have been used for the first time for the synthesis of novel β-amino phosphonates (chiral and achiral) by treatment with dialkyl phosphites using sodium hydride. 2-Substituted and 1,2-disubtituted β-amino phosphonates have efficiently been prepared following this method. The products are formed in high yield (79-84%) within 8-12 h.
Das, Biswanath,Reddy, Cheruku Ravindra,Nagendra, Siddavatam,Lingaiah, Maram
scheme or table
p. 3496 - 3498
(2011/07/08)

Enantiopure cyclic O-substituted phenylphosphonothioic acid: Synthesis and chirality-recognition ability
As a new acidic selector (resolving agent), we synthesized an enantiopure O-alkyl phenylphosphonothioic acid with a seven-membered ring ((R)-5), which was designed on the basis of the results for the enantioseparation of 1-arylethylamine derivatives with acyclic O-ethyl phenylphosphonothioic acid (I). The phosphonothioic acid (R)-5 showed unique chirality-recognition ability in the enantioseparation of 1-naphthylethylamine derivatives, aliphatic secondary amines, and amino alcohols; the ability was complementary to that of I. The X-ray crystallographic analyses of the less- and more-soluble diastereomeric salts showed that hydrogen-bonding networks in the salt crystals are 21-column-type with a single exception which is cluster-type. In the cases of the 21-column-type crystals, stability of the crystals is firstly governed by hydrogen bonds to form a 21-column and secondly determined by intra-columnar T-shaped CH/π interaction(s), intra-columnar hydrogen bond(s), inter-columnar van der Waals interaction and/or inter-columnar T-shaped CH/π interaction(s). In contrast, the cluster-type salt crystal is stabilized by the assistance of inter-cluster T-shaped CH/π and van der Waals interactions. To realize still more numbers of intra- and inter-columnar and -cluster T-shaped CH/π interactions, the seven-membered ring of (R)-5 plays a considerable role. Copyright
Ribeiro, Nigel,Kobayashi, Yuka,Maeda, Jin,Saigo, Kazuhiko
experimental part
p. 438 - 448
(2012/01/02)

From peptides to their alternating ester-urea analogues: Synthesis and influence of hydrogen bonding motif and stereochemistry on aggregation
(Chemical Equation Presented) Peptide-mimicking scaffolds with an incorporated ester-urea motif, replacing two adjacent amide residues, were synthesized and their aggregation behavior was studied in dependence of hydrogen bonding sites as well as backbone stereochemistry. Two oligomer series containing either 50% or 100% ester-urea units and either all-(L) or (D)-alt-(L) backbone configuration were prepared via ester and amide couplings, using a divergent/convergent exponential growth strategy. Their aggregation behavior in organic solution was investigated by means of concentration-dependent NMR spectroscopy and compared to the parent peptide series. Interestingly, the naturally occurring peptide scaffold exhibits the largest tendency to associate in combination with the strongest difference in aggregation behavior between all-(L) and (D)-alt-(L) backbone stereochemistry. With increasing incorporation of the ester-urea motif the aggregation strength decreases and become much less dependent on the backbone configuration. The obtained structure-aggregation relationships reveal the importance of the commensurability and multivalency of hydrogen bonding sites as well as conformational restriction for peptide association and should hence aid the design of peptide mimics, such as β -sheet breakers or gelators. 2009 American Chemical Society.
Hartwig, Sebastian,Schwarz, Jutta,Hecht, Stefan
supporting information; experimental part
p. 772 - 782
(2010/07/05)

Studies of the synthesis of all stereoisomers of MG-132 proteasome inhibitors in the tumor targeting approach
MG-132 is a tripeptide aldehyde (Z-L-leu-L-leu-L-leu-H, 2) proteasome inhibitor that exerts antitumor activity and enhances cytostatic/cytotoxic effects of chemo- and radiotherapy. Because of a troublesome synthesis of tripeptides with a non-natural configuration and modified side chains of amino acids, only two stereoisomers of MG-132 have been reported. Here, we propose a new approach to the synthesis of tripeptide aldehydes based on the Ugi reaction. Chiral, enantiomerically stable 2-isocyano-4-methylpentyl acetates were used as substrates for Ugi reaction resulting in a formation of tripeptide skeletons. Further functionalization of the obtained products led to a synthesis of tripeptide aldehydes. All stereoisomers of MG-132 were synthesized and studied as potential inhibitors of chymotrypsin-like, trypsin-like, and peptidylglutamyl peptide hydrolyzing activities of proteasome. These studies demonstrated the influence of absolute configuration of chiral aldehydes on the cytostatic/cytotoxic effects of the synthesized compounds and revealed that only (S,R,S)-(-)-2 stereoisomer is a more potent. proteasome inhibitor than MG-132.
Mroczkiewicz, Michal,Winkler, Katarzyna,Nowis, Dominika,Placha, Grzegorz,Golab, Jakub,Ostaszewski, Ryszard
experimental part
p. 1509 - 1518
(2010/08/03)

Total synthesis and absolute configuration of (-)-berkeleyamide A
[Chemical equation presented] A chiral-pool approach to (-)-berkeleyamide A 1 based on a diastereoselective nitrile oxide [3 + 2]-cycloaddition completes the first total synthesis establishing the absolute stereochemistry of the natural product.
Sperry, Jonathan,Harris, Eric B. J.,Brimble, Margaret A.
scheme or table
p. 420 - 423
(2010/04/26)

Addition of allylzinc to a-amino acid-derived imines: Synthesis of diamino alcohols by Hydroboration
Imines obtained by condensation of Z-pro- tected or Boc-protected α-amino aldehydes with α-amino tert-butyl esters or with O-silyl-protected amino alcohols were reacted with preformed allyl zinc yielding homoal- lylamines with yields around 50% and selectivities ranging from 50:50 to 90:10. Hydroboration of the terminal double bond furnished diamino alcohols with yields up to 97%. The configuration of the substrates was determined by X-ray-crystallographic analysis of a hydroboration product and comparison of physical data. Springer-Verlag 2010.
Virlouvet, Mickael,Goesmann, Helmut,Feldmann, Claus,Podlech, Joachim
experimental part
p. 177 - 198
(2010/08/05)

Synthesis and crystal structure of chiral N-ferrocenylmethyl alkamine imine
Two chiral ferrocenylimine alcohols have been prepared, [Fe(η5-(C5H5){η5-C 5H4CH=NCH(CH2OH)(CH2R)}] (R = Ph, 5a; R = Pri, 5b). Single crystal X-ray diffraction analysis reveals that the molecular structure of compound 5b is enantiomerically pure.
Zhang, Yu-Mei,Liu, Peng,Zhang, Hong-Li
experimental part
p. 665 - 667
(2010/03/24)

A new and general method for the synthesis of tripeptide aldehydes based on the multi-component Ugi reaction
Tripeptide aldehydes, such as Z-Leu-Leu-Leu-H (MG-132), are an important class of compounds due to their biological activity. A new, general method for the synthesis of tripeptide aldehydes based on the multi-component Ugi reaction was developed. A careful choice of isocyanides makes it possible to obtain tripeptide precursors whose functionalization led to target structures. This method can be used for the preparation of tripeptide aldehydes with non-natural amino acid side chains.
Mroczkiewicz, Micha?,Ostaszewski, Ryszard
experimental part
p. 4025 - 4034
(2009/09/30)

Design of a genetic algorithm for the simulated evolution of a library of asymmetric transfer hydrogenation catalysts
A library of catalysts was designed for asymmetric-hydrogen transfer to acetophenone. At first, the whole library was submitted to evaluation using high-throughput experiments (HTE). The catalysts were listed in ascending order, with respect to their performance, and best catalysts were identified. In the second step, various simulated evolution experiments, based on a genetic algorithm, were applied to this library. A small part of the library, called the mother generation (GO), thus evolved from generation to generation. The goal was to use our collection of HTE data to adjust the parameters of the genetic algorithm, in order to obtain a maximum of the best catalysts within a minimal number of gen-erations. It was namely found that simulated evolution's results depended on the selection of GO and that a random GO should be preferred. We also demonstrated that it was possible to get 5 to 6 of the ten best catalysts while investigating only 10% of the library. Moreover, we developed a double algorithm making this result still achievable if the evolution started with one of the worst GO.
Vriamont, Nicolas,Govaerts, Bernadette,Grenouillet, Pierre,De Bellefon, Claude,Oliant, Olivier
supporting information; scheme or table
p. 6267 - 6278
(2010/01/19)

(S)-N-(5-Chlorothiophene-2-sulfonyl)-β,β-diethylalaninol a Notch-1-sparing γ-secretase inhibitor
Accumulation of beta-amyloid (Aβ), produced by the proteolytic cleavage of amyloid precursor protein (APP) by β- and γ-secretase, is widely believed to be associated with Alzheimer's disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identification of the Notch-1-sparing (9.5-fold) γ-secretase inhibitor (S)-N-(5-chlorothiophene-2-sulfonyl)-β,β-diethylalaninol 7.b.2 (Aβ 40/42 EC50 = 28 nM), which is efficacious in reduction of Aβ production in vivo.
Cole, Derek C.,Stock, Joseph R.,Kreft, Anthony F.,Antane, Madelene,Aschmies, Suzan H.,Atchison, Kevin P.,Casebier, David S.,Comery, Thomas A.,Diamantidis, George,Ellingboe, John W.,Harrison, Boyd L.,Hu, Yun,Jin, Mei,Kubrak, Dennis M.,Lu, Peimin,Mann, Charles W.,Martone, Robert L.,Moore, William J.,Oganesian, Aram,Riddell, David R.,Sonnenberg-Reines, June,Sun, Shaiu-Ching,Wagner, Erik,Wang, Zheng,Woller, Kevin R.,Xu, Zheng,Zhou, Hua,Jacobsen, J. Steven
scheme or table
p. 926 - 929
(2009/09/06)

Syntheis of new chiral 5,6,7,8-tetrahydrotetrazolo[1,5-a]pyrazines from α-amino acid derivatives following "click" chemistry
An efficient and practical synthesis of new chiral fused tetrazoles have been synthesized following [3+2] cycloaddition reaction starting from α-amino acid derivatives.
Mohapatra, Debendra K.,Maity, Pradip K.,Ghorpade, Ravindra V.,Gurjar, Mukund K.
body text
p. 865 - 872
(2010/09/16)

Enantioselective syntheses of morpholines and their homologues via S N2-type ring opening of aziridines and azetidines with haloalcohols
(Chemical Equation Presented) A highly regio- and stereoselective strategy for the syntheses in high yield and enantioselectivity of a variety of substituted nonracemic morpholines and their homologues is described. The reaction proceeds via an SN2-type ring opening of activated aziridines and azetidines by suitable halogenated alcohols in the presence of Lewis acid followed by base-mediated intramolecular ring closure of the resulting haloalkoxy amine.
Ghorai, Manas K.,Shukla, Dipti,Das, Kalpataru
body text
p. 7013 - 7022
(2009/12/22)

Dynamic covalent self-assembled macrocycles prepared from 2-formyl-aryl-boronic acids and 1,2-amino alcohols
Reaction of 2-formyl-aryl-boronic acids with 1,2-amino alcohols results in dynamic covalent self assembly to quantitatively afford tetracyclic macrocyclic Schiff base boracycles containing bridging boron-oxygen-boron functionality. The Royal Society of Ch
Galbraith, Ewan,Kelly, Andrew M.,Fossey, John S.,Kociok-Koehn, Gabriele,Davidson, Matthew G.,Bull, Steven D.,James, Tony D.
p. 181 - 185
(2009/03/12)

Synthesis of chiral polydentate ligands and the use of their titanium complexes as pre-catalysts for the asymmetric trimethylsilylcyanation of benzaldehyde
A number of polydentate ligands based on enantiomerically pure binaphthol have been synthesized. The ligand complexes with titanium isopropoxide were used as catalysts for the asymmetric addition of trimethylsilyl cyanide to benzaldehyde. A fragment with axial chirality is responsible for the configuration of O-trimethylsilyl cyanohydrin product. In the case of the optimum ligand based on (R)-binaphthol and (S)-leucinol, an enantiomeric excess of 86% and quantitative yield were achieved in 4 h.
Belokon,Chusov,Skrupskaya,Bor'Kin,Yashkina,Lyssenko,Il'In,Strelkova,Timofeeva,Peregudov,North
experimental part
p. 1981 - 1988
(2009/12/23)

ANESTHETIC COMPOUNDS
In one embodiment the invention provides novel compounds of Formula (I) as well as prodrugs, salts, hydrates, solvates and N-oxides thereof. The invention also provides pharmaceutical compositions that include such compounds as well as methods for making and methods for using such compounds in medical therapy.
-
Page/Page column 35; 43

(2008/06/13)