- Method for catalyzing asymmetric Henry reaction of trifluoromethyl ketone
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The invention provides a method for catalyzing asymmetric Henry reaction of trifluoromethyl ketone. The method adopts a brand-new catalyst namely a compound shown as a formula I, and is simple to operate, high in substrate universality, high in reaction y
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Paragraph 0192; 0195-0196
(2021/03/06)
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- Aryl substituted aminotetrahydropyran compound and use thereof
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The invention relates to an aryl substituted aminotetrahydropyran compound and use thereof, and further relates to a pharmaceutical composition comprising the compound. The compound or pharmaceuticalcomposition provided by the invention can be used as a dipeptidyl peptidase-IV (DPP-IV) inhibitor.
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Paragraph 0368; 0372; 0373
(2019/07/04)
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- LZC696 intermediate and synthetic method therefor
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The invention discloses a compound which is (R)-tert-butyl(1,((1,1'biphenyl)-4-yl)3-((t-butyldimethylsilyl)oxo)propane-2-yl)carbamate, and the structural formula of the compound is as shown in formula A in the specification. An LZC696 intermediate is synthetized by adopting the compound, the whole technological process is free of expensive reagents or raw materials, free of sensitive reaction for oxygen and simple in purifying procedure, and commercial using purity can be achieved only by recrystallization purification of the compound 3 and the final product. The synthetic process of the invention is low in cost, simple and environmentally-friendly, and is suitable for industrial mass production.
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Paragraph 0070; 0071
(2016/10/09)
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- Total synthesis and activity of the metallo-β-lactamase inhibitor aspergillomarasmine A
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Resistance to β-lactam antibiotics is mediated primarily by enzymes that hydrolytically inactivate the drugs by one of two mechanisms: serine nucleophilic attack or metal-dependent activation of a water molecule. Serine β-lactamases are countered in the c
- Koteva, Kalinka,King, Andrew M.,Capretta, Alfredo,Wright, Gerard D.
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supporting information
p. 2210 - 2212
(2016/02/19)
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- Studies on the synthesis of orthogonally protected azalanthionines, and of routes towards β-methyl azalanthionines, by ring opening of N-activated aziridine-2-carboxylates
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Orthogonally protected azalanthionines were successfully synthesised by the ring-opening of N-activated aziridine-2-carboxylates with protected diaminopropanoic acids (DAPs). The required DAPs were also prepared by ring-opening of N-activated aziridine-2-carboxylates with para- methoxybenzylamine, but it was found that the choice of aziridine protecting groups dictated both the success of the reaction as well as the regioselectivity of the isolated products. Attempts to extend the methodology to the preparation of the more sterically demanding β-methyl azalanthionines have, so far, been unsuccessful.
- O'Brien, Keith,ó Proinsias, Keith,Kelleher, Fintan
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supporting information
p. 5082 - 5092
(2014/07/08)
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- Studies on the synthesis of orthogonally protected azalanthionines, and of routes towards β-methyl azalanthionines, by ring opening of N-activated aziridine-2-carboxylates
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Orthogonally protected azalanthionines were successfully synthesised by the ring-opening of N-activated aziridine-2-carboxylates with protected diaminopropanoic acids (DAPs). The required DAPs were also prepared by ring-opening of N-activated aziridine-2-carboxylates with para-methoxybenzylamine, but it was found that the choice of aziridine protecting groups dictated both the success of the reaction as well as the regioselectivity of the isolated products. Attempts to extend the methodology to the preparation of the more sterically demanding β-methyl azalanthionines have, so far, been unsuccessful.
- O'Brien, Keith,ó Proinsias, Keith,Kelleher, Fintan
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p. 5082 - 5092
(2014/12/10)
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- Proteomic searches comparing two (R)-lacosamide affinity baits: An electrophilic arylisothiocyanate and a photoactivated arylazide group
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We have advanced a novel strategy to search for lacosamide ((R)-1) targets in the brain proteome where protein binding is expected to be modest. Our approach used lacosamide agents containing "affinity bait" (AB) and "chemical reporter" (CR) units. The affinity bait moiety is designed to irreversibly react with the target, and the CR group permits protein detection and capture. In this study, we report the preparation and evaluation of (R)-N-(4-azido)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-3) and show that this compound exhibits potent anticonvulsant activities in the MES seizure model in rodents. We compared the utility of (R)-3 with its isostere, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-2), in proteomic studies designed to identify potential (R)-1 targets. We showed that despite the two-fold improved anticonvulsant activity of (R)-3 compared with (R)-2, (R)-2 was superior in revealing potential binding targets in the mouse brain soluble proteome. The difference in these agents' utility has been attributed to the reactivity of the affinity baits (i.e., (R)-2: aryl isothiocyanate moiety; (R)-3: photoactivated aryl azide intermediates) in the irreversible protein modification step, and we conclude that this factor is a critical determinant of successful target detection where ligand (drug) binding is modest. The utility of (R)-2 and (R)-3 in in situ proteome studies is explored.
- Park, Ki Duk,Stables, James P.,Liu, Rihe,Kohn, Harold
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scheme or table
p. 2803 - 2813
(2010/08/21)
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- Lacosamide isothiocyanate-based agents: Novel agents to target and identify lacosamide receptors
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(R)-Lacosamide ((R)-2, (R)-N-benzyl 2-acetamido-3-methoxypropionamide) has recently gained regulatory approval for the treatment of partial-onset seizures in adults.Whole animal pharmacological studies have documented that (R)-2 function is unique. A robust strategy is advanced for the discovery of interacting proteins associated with function and toxicity of (R)-2 through the use of (R)-2 analogues, 3, which contain "affinity bait (AB)" and "chemical reporter (CR)" functional groups. In 3, covalent modification of the interacting proteins proceeds at the AB moiety, and detection or isolation of the selectively captured protein occurs through the bioorthogonal CR group upon reaction with an appropriate probe. We report the synthesis, pharmacological evaluation, and interrogation of the mouse soluble brain proteome using 3 where the AB group is an isothiocyanate moiety. One compound, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy) propionamide ((R)-9), exhibited excellent seizure protection in mice, and like (R)-2, anticonvulsant activity principally resided in the (R)-stereoisomer. Several proteins were preferentially labeled by (R)-9 compared with (S)-9, including collapsin response mediator protein 2. 2009 American Chemical Society.
- Ki, Duk Park,Morieux, Pierre,Salomé, Christophe,Cotten, Steven W.,Reamtong, Onrapak,Eyers, Claire,Gaskell, Simon J.,Stables, James P.,Liu, Rihe,Kohn, Harold
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supporting information; experimental part
p. 6897 - 6911
(2010/04/24)
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- NOVEL N-BENZYLAMIDE SUBSTITUTED DERIVATIVES OF 2-(ACYLAMIDO)ACETIC ACID AND 2-(ACYLAMIDO)PROPIONIC ACIDS: POTENT NEUROLOGICAL AGENTS
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A first aspect of the invention is a compound (sometimes also referred to herein as an "active agent" or "active compound") of Formula (I) or ( Ia): or a pharmaceutically acceptable salt or prodrug thereof. Compositions thereof and methods of using the same (e.g. for the treatment of a neurological disease) are also described.
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Page/Page column 27-28
(2009/12/27)
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- DPP-IV INHIBITOR INCLUDING BETA-AMINO GROUP, PREPARATION METHOD THEREOF AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME FOR PREVENTING AND TREATING A DIABETES OR AN OBESITY
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The present invention provides a novel heterocyclic compound containing a beta-amino group, a method for preparing the same, and a pharmaceutical composition comprising the same heterocyclic compound or a pharmaceutically acceptable salt thereof as an act
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Page/Page column 12; 15-16
(2008/12/08)
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- A new and expeditious asymmetric synthesis of (R)- and (S)-2-aminoalkanesulfonic acids from chiral amino alcohols
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The mechanism for the transformation of β-amino alcohol methanesulfonate hydrochlorides into sodium β-amino alkanesulfonates using sodium sulfite was investigated. The results show that sodium sulfite initially neutralizes the β-amino alcohol methanesulfonate hydrochloride to give a free β-amino alcohol methanesulfonate, which then cyclizes to a 2-alkylaziridine. Attack by the previously formed sodium bisulfite at the less hindered carbon atom of the aziridine ring then yields a β-amino alkanesulfate sodium salt. Based on this mechanistic proposal, a new and rapid asymmetric synthesis of (R)- and (S)-2-aminoalkanesulfonic acids from chiral amino alcohols was developed. Chiral amino alcohols were converted to chiral aziridines through the Wenker method or Mitsunobu reaction and the resulting aziridines were reacted with sodium bisulfite to produce chiral β-amino alkanesulfonic acids.
- Xu, Jiaxi
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p. 1129 - 1134
(2007/10/03)
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- Efficient synthesis of (6R)-6-amino-1-methyl-4-(3-methylbenzyl)-hexahydro-1H-1,4-diazepine from methyl (2R)- and (2S)-1-benzyloxycarbonylaziridine-2-carboxylates
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An efficient and practical method for the synthesis of (6R)-6-amino-1-methyl-4-(3-methylbenzyl)hexahydro-1H-1,4-diazepine 2, which serves as the amine part of DAT-582, a potent and selective 5-HT3 receptor antagonist, is described. The key inte
- Kato, Shiro,Harada, Hiroshi,Morie, Toshiya
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p. 3219 - 3225
(2007/10/03)
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- Asymmetric Ketone Reduction using Chiral Oxazaborolidines derived from Aziridine Carbinols
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Asymmetric borane reduction of acetophenone using 1,3,2-oxazaborolidines derived from aziridine-2-tertiary alcohols 1 and 2 yielded the corresponding alcohol in high optical yields.The synthesis of the novel chiral catalysts 1 and 2 using D-and L-serine,
- Willems, Johannes G. H.,Dommerholt, F. Jan,Hammink, Jeannet B.,Vaarhorst, Ariaela M.,Thijs, Lambertus,Zwanenburg, Binne
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p. 603 - 606
(2007/10/02)
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- Versatile Synthesis of Stereospecifically Labelled D-Amino Acids via Labelled Aziridines - Preparation of (2R,3S)-- and (2R,3R)--Serine; (2S,2'S,3S,3'S)-- and (2S,2'S,3R,3'R)--Cystine; and (2S,3S)- and (2S,3R)--β-Chloroalanine
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Stereospecifically β-labelled protected 2-carboxyaziridines 2, with the stereochemistry of a D-amino acid at C-2, have been prepared by a chemicoenzymic synthesis.Preparation of the labelled malates 5, by hydration of fumaric acid using the enzyme fumarase or by amination with aspartase followed by nitrosation, was followed by conversion into the isoserines 3, by a process involving Curtius rearrangement with retention of stereochemistry at the chirally labelled primary centre.Protection and ring closure gave the aziridines 2, which, on ring opening with the appropriate nucleophiles and deprotection, gave stereospecifically labelled samples of D-serine 16, D-cystine 20 and β-chloro-D-alanine 22.
- Axelsson, B. Svante,O'Toole, Kevin J.,Spencer, Philip A.,Young, Douglas W.
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p. 807 - 816
(2007/10/02)
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