- Polysulfonate supported chiral diamine-nickel catalysts: Synthesis and applications
-
A series of chiral polysulfonate cyclohexyldiamine-Ni(II) catalysts were prepared via sulfur (VI) fluoride exchange click-reactions. The catalysts exhibited good catalytic activity and enantioselectivity in the Michael addition of malonates to nitroalkene
- Zhou, Jing-xuan,Zhu, Dong-yu,Chen, Jie,Zhang, Xue-jing,Yan, Ming,Chan, Albert S.C.
-
supporting information
(2021/01/25)
-
- COCRYSTALS OF (R)-BACLOFEN
-
The invention relates to novel cocrystals of (R)-Baclofen and processes for preparation thereof, and in particular to cocrystals of (R)-Baclofen with cinnamic acid, benzoic acid, salicylic acid and ferulic acid. It also refers to pharmaceutical compositions containing said cocrystals and to a use of said cocrystals or pharmaceutical compositions for the treatment of a disease or disorder selected from spasticity due to multiple sclerosis, spinal cord injury or cerebral palsy, and alcoholism.
- -
-
Page/Page column 23; 24
(2020/07/21)
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- Assembling of medium/long chain-based β-arylated unnatural amino acid derivatives via the Pd(II)-catalyzed sp3 β-C-H arylation and a short route for rolipram-type derivatives
-
In this paper, we report the assembling of libraries of β-arylated short/medium/long chain-based non-α-amino acid (aminoalkanoic acid) derivatives via the Pd(II)-catalyzed, bidentate directing group 8-aminoquinoline-aided sp3 β-C-H activation/arylation method. Short/medium chain-based unnatural amino acid derivatives containing an aryl group at the β-position are promising small molecules with therapeutic properties. Thus, it is necessary to enrich the libraries of short/medium/long chain-based unnatural amino acid derivatives containing an aryl group at the β-position. Considering the importance of β-arylated short/medium/long chain-based non-α-amino acid derivatives, an inclusive attention was paid to explore the Pd(II)-catalyzed sp3 β-C-H arylation of short/medium/long chain-based non-α-amino acids. Representative synthetic transformations including a short route for the assembling of rolipram and related compounds and 3-arylated GABA derivatives such as, baclofen, phenibut and tolibut were shown using selected β-C-H arylated non-α-amino acid derivatives.
- Tomar, Radha,Bhattacharya, Debabrata,Babu, Srinivasarao Arulananda
-
p. 2447 - 2465
(2019/03/26)
-
- Highly Enantioselective Synthesis of Chiral γ-Lactams by Rh-Catalyzed Asymmetric Hydrogenation
-
A Rh/bisphosphine-thiourea (ZhaoPhos) catalytic system has been identified for the straightforward asymmetric synthesis of chiral γ-lactams. A variety of NH free α,β-unsaturated lactams bearing a β-aryl or β-alkyl substituent were smoothly hydrogenated to
- Lang, Qiwei,Gu, Guoxian,Cheng, Yaoti,Yin, Qin,Zhang, Xumu
-
p. 4824 - 4828
(2018/06/08)
-
- A novel method for the synthesis of racemic pregabalin, baclofen and 3-phenibut involving lossen rearrangement
-
Pregabalin,baclofen,and3-phenibutareγ-aminobutyricacid receptorsusedasanticonvulsant agents. The racemic forms of these anticonvulsants have been prepared by Lossen rearrangement. This procedure also provides an easy method to prepare carbamates useful intermediates to prepare anticonvulsants. This process is economical and easy to scale-up and yields are good.
- Ponnusamy, Kannan,Davis Presley,Nagapillai, Prakash,Deivanayagam, Eswaramoorthy
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p. 275 - 278
(2018/09/14)
-
- A Versatile Route to Unstable Diazo Compounds via Oxadiazolines and their Use in Aryl–Alkyl Cross-Coupling Reactions
-
Coupling of readily available boronic acids and diazo compounds has emerged recently as a powerful metal-free carbon–carbon bond forming method. However, the difficulty in forming the unstable diazo compound partner in a mild fashion has hitherto limited their general use and the scope of the transformation. Here, we report the application of oxadiazolines as precursors for the generation of an unstable family of diazo compounds using flow UV photolysis and their first use in divergent protodeboronative and oxidative C(sp2)?C(sp3) cross-coupling processes, with excellent functional-group tolerance.
- Greb, Andreas,Poh, Jian-Siang,Greed, Stephanie,Battilocchio, Claudio,Pasau, Patrick,Blakemore, David C.,Ley, Steven V.
-
p. 16602 - 16605
(2017/12/13)
-
- New multicomponent reaction for the direct synthesis of β-aryl-γ-nitroesters promoted by hydrotalcite-derived mixed oxides as heterogeneous catalyst
-
A new approach based on multicomponent/domino combined reactions for the synthesis of γ-nitroesters promoted by a mixed aluminium-magnesium oxides derived from hydrotalcite-like material was developed. Different γ-nitroesters were synthesized in 15-95percent yield using Meldrum's acid, aromatic aldehydes, nitromethane and different alcohols as reagents and solvents. The γ-aminobutyric acid derivatives, Phenibut and Baclofen, were prepared in 63 and 61percent overall yield, respectively, through a two steps synthetic strategy. A mechanistic pathway was proposed based on the gas chromatography mass spectrometry (GC-MS) and electrospray ionization mass spectrometry (ESI-MS) experiments.
- D'Oca, Caroline R. M.,Naciuk, Fabricio F.,Silva, Jéssica C.,Guedes, Esthéfani P.,Moro, Celso C.,D'Oca, Marcelo G. M.,Santos, Leonardo S.,Natchigall, Fabiane M.,Russowsky, Dennis
-
p. 285 - 298
(2016/12/18)
-
- Enantioselective conjugate hydrocyanation of α,β-unsaturated N-acylpyrroles catalyzed by chiral lithium(I) phosphoryl phenoxide
-
Enantioselective conjugate hydrocyanation of α,β-unsaturated N-acylpyrroles with the combined use of Me3SiCN, LiCN, and HCN has been developed in the presence of a chiral lithium(I) phosphoryl phenoxide catalyst. This reaction is useful for a v
- Hatano, Manabu,Yamakawa, Katsuya,Ishihara, Kazuaki
-
p. 6686 - 6690
(2017/11/09)
-
- Squaramide-Catalyzed Michael Addition as a Key Step for the Direct Synthesis of GABAergic Drugs
-
Enantioselective organocatalytic Michael additions serve as the key step in syntheses of chiral drugs based on γ-aminobutyric acid. The applicability of various squaramide catalysts for these Michael-type reactions has been assessed. Very good results in
- Veverková, Eva,Bilka, Stanislav,Baran, Rastislav,?ebesta, Radovan
-
p. 1474 - 1482
(2016/05/24)
-
- A synthetic γ-amino butyric acid kind of chiral the method for preparing the compound of
-
The invention discloses a method for synthesizing a gamma-aminobutyric acid chiral compound. The method comprises the following steps of: adding nitroolefin and malonate to a solvent in the presence of a catalyst A and an additive; carrying out conjugate
- -
-
Paragraph 0029; 0039
(2017/03/17)
-
- Efficient synthesis of β-aryl-γ-lactams and their resolution with (S)-Naproxen: Preparation of (R)- and (S)-Baclofen
-
An efficient synthesis of enantiomerically-pure β-aryl-γ-lactams is described. The principal feature of this synthesis is the practical resolution of β-aryl-γ-lactams with (S)-Naproxen. The procedure is based on the Michael addition of nitromethane to benzylidenemalonates, which was easily obtained, followed by the reduction of the γ-nitroester in the presence of Raney nickel and the subsequent saponification/decarboxylation reaction. The utility of this methodology was highlighted by the preparation of enantiomerically-pure (R)- and (S)-Baclofen hydrochloride.
- Montoya-Balbás, Iris J.,Valentín-Guevara, Berenice,López-Mendoza, Estefanía,Linzaga-Elizalde, Irma,Ordo?ez, Mario,Román-Bravo, Perla
-
p. 22028 - 22043
(2016/01/25)
-
- One pot domino reaction accessing γ-nitroesters: Synthesis of GABA derivatives
-
Michael addition of 1,3-dicarbonyl compounds to nitrostyrenes is efficiently promoted by hydrotalcite [Mg-Al] to afford the respective γ-nitrodicarbonyl adducts. Differently, the addition of Meldrum's acid leads to a direct access of γ-nitroesters through a one pot domino process. GABA derivatives (+/-)-phenibut and (+/-)-baclofen were readily synthesized from the respective nitro adducts.
- Naciuk, Fabricio F.,Vargas, Debora Z.,D'oca, Caroline R. M.,Moro, Celso C.,Russowsky, Dennis
-
p. 1643 - 1653
(2015/03/18)
-
- Highly Enantioselective Michael Addition of Nitroalkanes to Enones and Its Application in Syntheses of (R)-Baclofen and (R)-Phenibut
-
A highly enantioselective Michael addition of nitroalkanes to α,β-unsaturated ketones was developed. In the presence of a chiral primary amine-thiourea catalyst based on dehydroabietic amine, γ-nitro ketones were obtained with excellent enantioselectiviti
- Guo, Xing-Tao,Shen, Jie,Sha, Feng,Wu, Xin-Yan
-
p. 2063 - 2072
(2015/07/15)
-
- Opposite enantioselectivity in the bioreduction of (Z)-β-aryl-β-cyanoacrylates mediated by the tryptophan 116 mutants of old yellow enzyme 1: Synthetic approach to (R)- and (S)-β-aryl-γ-lactams
-
The Trp 116 mutants of Old Yellow Enzyme 1 that catalyse the reduction of (Z)-β-aryl-β-cyanoacrylates give the opposite enantioselectivity according to the nature of the amino acid in position 116. Small amino acids (e.g., alanine) make the substrate bind
- Brenna, Elisabetta,Crotti, Michele,Gatti, Francesco G.,Monti, Daniela,Parmeggiani, Fabio,Powell, Robert W.,Santangelo, Sara,Stewart, Jon D.
-
p. 1849 - 1860
(2015/06/02)
-
- Multisite organic-inorganic hybrid catalysts for the direct sustainable synthesis of GABAergic drugs
-
Multisite organic-inorganic hybrid catalysts have been prepared and applied in a new general, practical, and sustainable synthetic procedure toward industrially relevant GABA derivatives. The domino sequence is composed of seven chemical transformations which are performed in two one-pot reactions. The method produces both enantiomeric forms of the product in high enantiopurity as well as the racemate in good yields after a single column purification step. This protocol highlights major process intensification, catalyst recyclability, and low waste generation.
- Leyva-Perez, Antonio,Garcia-Garcia, Pilar,Corma, Avelino
-
supporting information
p. 8687 - 8690
(2014/08/18)
-
- ALLOSTERIC PROTEIN KINASE MODULATORS
-
The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.
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-
Page/Page column 45
(2012/03/10)
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- Regio- and enantioselective palladium-catalyzed allylic alkylation of nitromethane with monosubstituted allyl substrates: Synthesis of (R)-rolipram and (R)-baclofen
-
The Pd-catalyzed asymmetric allylic alkylation (AAA) reaction of nitromethane with monosubstituted allyl substrates was realized for the first time to provide corresponding products in high yields with excellent regio- and enantioselectivities. The protocol was applied to the enantioselective synthesis of (R)-baclofen and (R)-rolipram.
- Yang, Xiao-Fei,Ding, Chang-Hua,Li, Xiao-Hui,Huang, Jian-Qiang,Hou, Xue-Long,Dai, Li-Xin,Wang, Pin-Jie
-
p. 8980 - 8985,6
(2012/12/12)
-
- Regio- and enantioselective palladium-catalyzed allylic alkylation of nitromethane with monosubstituted allyl substrates: Synthesis of (R)-rolipram and (R)-baclofen
-
The Pd-catalyzed asymmetric allylic alkylation (AAA) reaction of nitromethane with monosubstituted allyl substrates was realized for the first time to provide corresponding products in high yields with excellent regio- and enantioselectivities. The protocol was applied to the enantioselective synthesis of (R)-baclofen and (R)-rolipram.
- Yang, Xiao-Fei,Ding, Chang-Hua,Li, Xiao-Hui,Huang, Jian-Qiang,Hou, Xue-Long,Dai, Li-Xin,Wang, Pin-Jie
-
p. 8980 - 8985
(2013/01/15)
-
- Asymmetric synthesis of β-substituted γ-lactams via rhodium/diene-catalyzed 1,4-additions: Application to the synthesis of (R)-baclofen and (R)-rolipram
-
An efficient rhodium/diene-catalyzed asymmetric addition of arylboronic acids to α,β-unsaturated γ-lactams has been developed. The power of this methodology is further demonstrated by the concise synthesis of (R)-baclofen and (R)-rolipram.
- Shao, Cheng,Yu, Hong-Jie,Wu, Nuo-Yi,Tian, Ping,Wang, Rui,Feng, Chen-Guo,Lin, Guo-Qiang
-
supporting information; experimental part
p. 788 - 791
(2011/04/16)
-
- Biscinchona alkaloids as highly efficient bifunctional organocatalysts for the asymmetric conjugate addition of malonates to nitroalkenes at ambient temperature
-
The novel bifunctional bisalkaloids have been developed as highly efficient catalysts for the asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes with low catalyst loading (1 mol %) at ambient temperature, providing the products with
- Li, Fei,Li, Ying-Zi,Jia, Zhen-Shan,Xu, Ming-Hua,Tian, Ping,Lin, Guo-Qiang
-
experimental part
p. 10186 - 10194
(2012/01/03)
-
- Rhodium-catalyzed asymmetric addition of arylboronic acids to γ-phthalimido-substituted-α,β-unsaturated carboxylic acid esters: An approach to γ-amino acids
-
Efficient Rh-catalyzed asymmetric 1,4-addition of arylboronic acids to ethyl-γ-phthalimidocrotonate by using bis-sulfoxide ligand affords γ-aminobutyric acid (GABA) derivatives with high enantioselectivities (90-96% ee) under mild conditions. Optically pu
- Han, Fuzhong,Chen, Jun,Zhang, Xiangyang,Liu, Jibing,Cun, Linfeng,Zhu, Jin,Deng, Jingen,Liao, Jian
-
supporting information; experimental part
p. 830 - 833
(2011/03/20)
-
- A short, chemoenzymatic route to chiral β-aryl-γ-amino acids using reductases from anaerobic bacteria
-
A short chemoenzymatic synthesis of β-aryl-γ-aminobutyric acids has been developed, based on a highly enantioselective biocatalytic reduction of β-aryl-β-cyano-α,β-unsaturated carboxylic acids.
- Fryszkowska, Anna,Fisher, Karl,Gardiner, John M.,Stephens, Gill M.
-
supporting information; scheme or table
p. 533 - 535
(2010/05/11)
-
- Method of Producing Optically Active 4-Amino-3-Substituted Phenylbutanoic Acid
-
The present invention provides a method of producing a compound (IIa) or a compound (IIb), provides a method of producing a compound (IIIa) or a compound (IIIb), provides a method of producing a compound (Va) or its salt or a compound (Vb) or its salt, provides a method of producing a compound (IIIa) or a compound (IIIb), further, provides a method of producing a compound (Va) or its salt or a compound (Vb) or its salt including these production methods.
- -
-
Page/Page column 12
(2009/06/27)
-
- Highly enantioselective organocatalytic conjugate addition of nitromethane to α,β-unsaturated aldehydes: Three-step synthesis of optically active baclofen
-
An efficient, organocatalytic, highly enantioselective, conjugate addition reaction of nitromethane with α,β-unsaturated aldehydes has been developed. The process serves as the key step for a practical 3-step synthesis of chiral baclofen, an antispastic drug.
- Zu, Liansuo,Xie, Hexin,Li, Hao,Wang, Jian,Wang, Wei
-
p. 2660 - 2664
(2008/09/19)
-
- Diastereoselective conjugate addition of cyanide to α,β- unsaturated oxazolidinones: Enantioselective synthesis of ent-pregabalin and baclofen
-
Conjugate addition of cyanide to chiral α,β-unsaturated oxazolidinones catalyzed by samarium(III) isopropoxide proceeds with good diastereoselectivity. The addition products can be converted into the biologically active targets ent-pregabalin and baclofen
- Armstrong, Alan,Convine, Nicola J.,Popkin, Matthew E.
-
p. 1589 - 1591
(2007/10/03)
-
- Co-catalyzed reductive cyclization of azido and cyano substituted α,β-unsaturated esters with NaBH4: enantioselective synthesis of (R)-baclofen and (R)-rolipram
-
Sodium borohydride in combination with a catalytic amount of CoCl2 has been found to be an excellent catalytic system in reductive cyclizations of suitably substituted azido and cyano groups of α,β-unsaturated esters to afford γ and δ-lactams in high yields. The process has been demonstrated for the enantioselective synthesis of (R)-baclofen, (R)-rolipram, and (R)-4-fluorophenylpiperidinone, a key intermediate for (-)-paroxetine.
- Paraskar, Abhimanyu S.,Sudalai, Arumugam
-
p. 4907 - 4916
(2007/10/03)
-
- Enantio- and diastereoselective michael reaction of 1,3-dicarbonyl compounds to nitroolefins catalyzed by a bifunctional thiourea
-
We synthesized a new class of bifunctional catalysts bearing a thiourea moiety and an amino group on a chiral scaffold. Among them, thiourea 1e bearing 3,5-bis(trifluoromethyl)benzene and dimethylamino groups was revealed to be highly efficient for the as
- Okino, Tomotaka,Hoashi, Yasutaka,Furukawa, Tomihiro,Xu, Xuenong,Takemoto, Yoshiji
-
p. 119 - 125
(2007/10/03)
-
- Asymmetric synthesis of β-substituted γ-lactams employing the samp-/ramp-hydrazone methodology. Application to the synthesis of (R-(-)-baclofen
-
A short and efficient asymmetric synthesis of β-substituted γ-lactams is described. Key steps are the α-alkylation of aldehyde SAMP-hydrazones with alkyl bromoacetates, their MMPP mediated conversion to the corresponding nitriles and a reductive cyclization with Raney Ni or Ni boride to the title pyrrolidin-2-ones. The β-substituted γ-lactams are obtained in three steps, good overall yields (27-78%) and excellent enantiomeric excesses (ee=93-99%). The applicability of this procedure for the asymmetric synthesis of GABAs (γ-aminobutyric acids) is demonstrated for (R-(-)-baclofen hydrochloride, which is obtained in 4 steps 55% yield and 94% ee.
- Enders, Dieter,Niemier, Oliver
-
p. 385 - 403
(2007/10/03)
-
- Synthesis of both enantiomers of baclofen using (R)- and (S)-N-phenylpantolactam as chiral auxiliaries
-
Esterification of racemic 4-nitro-3-(4-chlorophenyl)butanoic acid with (R)- or (S)-N-phenylpantolactam as the chiral auxiliary allowed us to obtain the (3R,3′R)- or (3S,3′S)-nitro esters with >98:2 dr after column chromatography. Hydrolysis of the resulti
- Camps, Pelayo,Munoz-Torrero, Diego,Sanchez, Laura
-
p. 2039 - 2044
(2007/10/03)
-
- A facile synthesis of 3-aryl pyroglutamic acid. Facile synthesis of baclofen and chlorpheg
-
A facile synthesis of 3-aryl pyroglutamic acids via stepwise [3+2] annulation and desulfonated hydrolysis is reported. Base-induced coupling/cyclization reactions of α-sulfonylacetamide with various β-functional groups of (Z)-2-bromoacrylates yielded three contiguous chiral centers on the polysubstituted pyroglutamates system with trans-trans orientation in a one-pot synthesis. This facile strategy was used to synthesize amino acid derivatives baclofen and chlorpheg.
- Chang, Meng-Yang,Sun, Pei-Pei,Chen, Shui-Tein,Chang, Nein-Chen
-
p. 5271 - 5273
(2007/10/03)
-
- Enantioselective Michael addition of nitromethane to α,β-enones catalyzed by chiral quaternary ammonium salts. A simple synthesis of (R)-baclofen
-
(equation presented) R/S = 85/15, 97.5/2 after recryst. Enantioselective Michael addition of nitromethane to an α,β-enone is a key step in the synthesis of (R)-baclofen.
- Corey,Zhang, Fu-Yao
-
p. 4257 - 4258
(2007/10/03)
-
- Enantioselective synthesis of 4-substituted 2-pyrrolidinones by site- selective C-H insertion of α-methoxycarbonyl-α-diazoacetanilides catalyzed by dirhodium(II) tetrakis[N-phthaloyl-(S)-tert-leucinate]
-
Site- and enantioselective intramolecular C-H insertion of α- methoxycarbonyl-α-diazoacetamides has been achieved by exploiting a p- nitrophenyl group as the N-substituent and dirhodium(II) tetrakis[N- phthaloyl-(S)-tert-leucinate] as catalyst, leading to the formation of 4 substituted 2-pyrrolidinone derivatives of up to 82% ee. The efficiency of the present protocol has been verified well by a short-step synthesis of (R)- (-)-baclofen.
- Anada, Masahiro,Hashimoto, Shun-Ichi
-
-
- A simple and efficient new approach to the total synthesis of (±)-4- amino-3-(4-chlorophenyl)-butyric acid (BACLOFEN)
-
Based on the utilization of a [2+21 cycloaddition reaction between dichloroketene and an appropriated olefin as a key step, we describe a new and simple four step approach to the total synthesis of (±)-4-amino-3-(4- chlorophenyl)-butyric acid (BACLOFEN),
- Coelho, Fernando,De Azevedo, Mariangela B. M.,Boschiero, Roberta,Resende, Patricia
-
p. 2455 - 2465
(2007/10/03)
-
- An efficient synthesis of (±)-4-amino-3-(4-chlorophenyl)-butyric acid. (baclofen)
-
A new preparation of baclofen is proposed. The key step involved a regioselective ring opening of 2-phenylaziridine with allylmagnesium bromide. Further oxidation of the side chain gives access to 4-phenyl-pyrrolidin-2-one and to baclofen.
- Ibuka,Schoenfelder,Bildstein,Mann
-
p. 1777 - 1782
(2007/10/02)
-
- Chemoenzymatic synthesis of both enantiomers of baclofen
-
Both enantiomers of baclofen have been synthesized in five steps from 4-chlorocinnamic acid. The key step is the highly stereoselective enzymatic hydrolysis of dimethyl 3-(4-chlorophenyl)glutarate by chymotrypsin.
- Chenevert, Robert,Desjardins, Michel
-
p. 4249 - 4250
(2007/10/02)
-