- Asymmetric Dearomative Cascade Multiple Functionalizations of Activated N-Alkylpyridinium and N-Alkylquinolinium Salts
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An enantioselective cascade reaction of N-alkylpyridinium and -quinolinium salts with o-hydroxybenzylideneacetones to access fused polyheterocycles through cross dienamine-mediated addition followed by trapping of the dearomatized enamine-type intermediates and aminal formation has been developed. A cascade assembly of N-benzyl-4-methylpyridinium salt and cyclic 2,4-dienones is further disclosed to give bridged frameworks via repetitive dearomatization and aromatization activation.
- Chen, Ying-Chun,Du, Wei,Song, Xue,Yan, Ru-Jie
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supporting information
p. 7617 - 7621
(2020/10/09)
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- A new type of L-Tertiary leucine-derived ligand: Synthesis and application in Cu(II)-catalyzed asymmetric Henry reactions
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A new series of Schiff bases derived from amino acids were developed as chiral ligands for Cu(II)-catalyzed asymmetric Henry reactions. The optimum ligand 7d exhibited outstanding catalytic efficiency in the Cu(II)-catalyzed asymmetric Henry additions of four nitroalkanes to different kinds of aldehydes to produce 76 desired adducts in high yields (up to 96%) with excellent enantioselectivities, up to 99% enantiomeric excess (ee).
- Cai, Zedong,Lan, Ting,Ma, Pengfei,Zhang, Jingfang,Yang, Qingqing,He, Wei
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- Dynamic Kinetic Resolution of N-Protected Amino Acid Esters via Phase-Transfer Catalytic Base Hydrolysis
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Asymmetric base hydrolysis of α-chiral esters with synthetic small-molecule catalysts is described. Quaternary ammonium salts derived from quinine were used as chiral phase-transfer catalysts to promote the base hydrolysis of N-protected amino acid hexafluoroisopropyl esters in a CHCl3/NaOH (aq) via dynamic kinetic resolution, providing the corresponding products in moderate to good yields (up to 99%) with up to 96:4 er. Experimental and computational mechanistic studies using DFT calculation and pseudotransition state (pseudo-TS) conformational search afforded a TS model accounting for the origin of the stereoselectivity. The model suggested π-stacking and H-bonding interactions play essential roles in stabilizing the TS structures.
- Yamamoto, Eiji,Wakafuji, Kodai,Furutachi, Yuho,Kobayashi, Kaoru,Kamachi, Takashi,Tokunaga, Makoto
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p. 5708 - 5713
(2018/05/30)
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- Asymmetric Propargylboration of Aldimines and Ketimines with the Borabicyclo[3.3.2]decanes: Novel Entries to Allenyl Carbinamines, Amino Acids, and Their α-Methyl Counterparts
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Available in either enantiomerically pure form through quantitative Grignard procedures from air-stable crystalline complexes (1, 3), the B-γ-TMS propargylic derivatives of the 10-TMS- (2) and 10-phenyl-9-borabicyclo[3.3.2]decanes (4) provide highly selec
- Alicea-Matías, Eyleen,Soderquist, John A.
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p. 336 - 339
(2017/04/21)
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- COMPOUNDS AND RELATED METHODS OF USE
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Described herein are compounds of formula (I), related compositions, and their use, for example in the formation of α-amino acids or a precursor thereof such as an α-aminonitrile.
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- HYDANTOIN DERIVATIVES USEFUL AS KV3 INHIBITORS
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The invention provides compounds of formula (I): Said compounds being inhibitors of Kv3 channels and of use in the prophylaxis or treatment of related disorders.
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Paragraph 0708-0710
(2013/10/22)
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- PROCESS FOR PRODUCTION OF N-ALKOXYCARBONYL-tert-LEUCINES
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A high quality N-alcoxycarbonyl-tert leucine can be efficiently and stably produced with an easy procedure by reacting tert-leucine with an N-alcoxycarbonylating agent in the presence of water, wherein the use amount of the N-alcoxycarbonylating agent is not less than 0.90 times by mole and not more than 1.00 times by mole relative to the tert-leucine, with maintaining the pH of the reaction mixture in the range of not less than 9 and not more than 13 using a basic agent. In addition, an N-alcoxycarbonyl-tert-leucine can be efficiently extracted from the basic aqueous solution thereof under a mild condition using a water-immiscible solvent by mixing a hydroxide. Furthermore, the two crystal forms of N-butoxycarbonyl-tert-leucine can be controlled by adjusting the water amount in crystallization step, and the compound can be stably produced in an industrial production.
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Page/Page column 14
(2012/03/26)
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- HYDANTOIN DERIVATIVES USEFUL AS KV3 INHIBITORS
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The invention provides compounds of formula (I): Said compounds being inhibitors of Kv3 channels and of use in the prophylaxis or treatment of related disorders.
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Page/Page column 97
(2012/06/30)
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- IMIDAZOLIDINEDIONE DERIVATIVES
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The invention provides a compound of formula (Ia), and pharmaceutically acceptable salts thereof. The invention also provides use of the compounds or salts as modulators of Kv3.1 and/or Kv3.2, and in the treatment of diseases or disorders where a modulator of Kv3.1 and/or Kv3.2 is required, such as depression and mood disorders, hearing disorders, schizopherenea, substance abuse disorders, sleep disorders or epilepsy.
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Page/Page column 77
(2011/06/26)
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- Primary amino acid derivatives: Compounds with anticonvulsant and neuropathic pain protection activities
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Pharmacological management remains the primary method to treat epilepsy and neuropathic pain. We have advanced a novel class of anticonvulsants termed functionalized amino acids (FAAs). In this study, we examine FAA derivatives from which the terminal acetyl moiety was removed and termed these compounds primary amino acid derivatives (PAADs). Twenty-seven PAADs were prepared; the central C(2) R-substituent was varied, including C(2) stereochemistry, and the compounds were tested in rodent models of seizures and neuropathic pain. C(2)-Hydrocarbon N-benzylamide PAADs were potent anticonvulsants and excellent anticonvulsant activity (mice, ip; rat, po) was observed for C(2) R-substituted PAADs in which the R group was ethyl, isopropyl, or tert-butyl, and the C(2) stereochemistry conformed to the d-amino acid configuration ((R)-stereoisomer). These values surpassed the activities of several clinical antiepileptic drugs. The C(2) (R)-ethyl and C(2) (R)-isopropyl PAADs also displayed excellent activities in the mouse (ip) formalin neuropathic pain model. Significantly, unlike the FAA structure-activity relationship, PAAD anticonvulsant activity increased upon substitution of a methylene unit for a heteroatom in the R-substituent that was one atom removed from the C(2) site, suggesting that these PAADs function by a different pathway than FAAs.
- King, Amber M.,Salomé, Christophe,Dinsmore, Jason,Salomé-Grosjean, Elise,De Ryck, Marc,Kaminski, Rafal,Valade, Anne,Kohn, Harold
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supporting information; experimental part
p. 4815 - 4830
(2011/10/01)
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- Asymmetric synthesis of 2,3-dihydro-2-arylquinazolin-4-ones: Methodology and application to a potent fluorescent tubulin inhibitor with anticancer activity
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For several decades the 2,3-dihydroquinazolinone (DHQZ) heterocycle has been known to possess a variety of important biological and medicinal properties. Despite the many interesting facets of these molecules, synthetic access to nonracemic DHQZ analogues has remained elusive. Herein, we disclose a synthetic route that allows access to either enantiomer of a variety of DHQZ derivatives. We illustrate the utility of this chemistry with the asymmetric preparation and biological evaluation of a new chiral fluorescent tubulin binding agent with extremely potent antiproliferative properties against human cancer cells. A computational rationale for the increased potency of the (S)-enantiomer over the (R)-enantiomer is given, based on the crystal structure of αβ-tubulin complexed with colchicine. Taking advantage of the inherent fluorescence of these molecules, confocal images of GMC-5-193 (compound 7) in the cytoplasm of human melanoma cells (MDA-MB-435) cells are presented.
- Chinigo, Gary M.,Paige, Mikell,Grindrod, Scott,Hamel, Ernest,Dakshanamurthy, Sivanesan,Chruszcz, Maksymilian,Minor, Wladek,Brown, Milton L.
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experimental part
p. 4620 - 4631
(2009/06/06)
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- Enzymatic approach to both enantiomers of N-Boc hydrophobic amino acids
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Protease catalysed hydrolysis of N-Boc-amino acid esters allows us to obtain N-Boc l-acids and d-esters of amino butanoic acid, nor-leucine, nor-valine, leucine and t-leucine in excellent ee. The reaction occurs in short reaction times and high concentrations. When a biphasic system (buffer-MTBE) is employed, a strong solvent effect is observed. This method could be of significance for the preparation of d-t-leucine, for which a practical method is currently unavailable.
- Agosta, Eleonora,Caligiuri, Antonio,D'Arrigo, Paola,Servi, Stefano,Tessaro, Davide,Canevotti, Renato
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p. 1995 - 1999
(2007/10/03)
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- Chiral electrophilic 'glycinal' equivalents. New synthons for optically active α-amino acids and 4-substituted 2-oxazolidinones
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The thermal reaction of 3-[(1S)-2-alkoxy-1-apocamphanecarbonyl]-2-oxazolones (21a-c) with dialkyl azodicarboxylates (9) results in exclusive formation of [4 + 2] type cycloadducts (22 and 23) with moderate levels of diastereofacial selection (up to 72% d.e.). The diastereomers thus obtained were readily purified and subsequent treatment with acidic methanol followed by removal of the auxiliary with LiBH4/MeOH (1:2) gave optically pure 4-methoxy-5-hydrazino-2-oxazolidinones (26 and 27), which serve as α-aminoaldehyde templates useful for the synthesis of a wide variety of optically active α-amino acids as well as 4-alkyl and 4-aryl-2-oxazolidinones.
- Matsunaga, Hirofumi,Ishizuka, Tadao,Kunieda, Takehisa
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p. 1275 - 1294
(2007/10/03)
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- Versatile routes to chiral 4-substituted 2-oxazolindinones and α-amino acids. Use of chiron, [4 + 2] cycloadducts of dialkyl azodi-carboxylates and 2-oxazolones
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The thermal reaction of 3-[(1S)-2-alkoxy-1-apocamphanecarbonyl]-2-oxazolones with dialkyl azodicarboxylates results in exclusive formation of [4 + 2] type cycloadducts with moderate levels of diastereofacial selection, which serve as versatile chiral synthons for a wide variety of 4-alkyl and 4-alkyl-2-oxazolidinones as well as α-amino acids.
- Matsunaga,Ishizuka,Marubayashi,Kunieda
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p. 1077 - 1079
(2007/10/02)
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