- Chiral guanidine catalyzed acylative kinetic resolution of racemic 2-bromo-1-arylethanols
-
In this study, chiral guanidine catalyzed acylative kinetic resolution of racemic 2-bromo-1-arylethanols was achieved with high selectivity. Irrespective of the electronic nature and the substitution patterns on the aromatic rings, a variety of substrates were suitable for this reaction. The branched acyl component was considered to be optimal for obtaining high s-values. The transition state of the reaction was proposed based on the absolute configuration of the obtained product.
- Sawada, Erika,Nakata, Kenya
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p. 371 - 373
(2021/03/16)
-
- Regioselective Sulfonylation/Acylation of Carbohydrates Catalyzed by FeCl3 Combined with Benzoyltrifluoroacetone and Its Mechanism Study
-
A catalytic amount of FeCl3 combined with benzoyl trifluoroacetone (Hbtfa) (FeCl3/Hbtfa = 1/2) was used to catalyze sulfonylation/acylation of diols and polyols using diisopropylethylamine (DIPEA) or potassium carbonate (K2CO3) as a base. The catalytic system exhibited high catalytic activity, leading to excellent isolated yields of sulfonylation/acylation products with high regioselectivities. Mechanism studies indicated that FeCl3 initially formed [Fe(btfa)3] (btfa = benzoyl trifluoroacetonate) with twice the amount of Hbtfa under basic conditions in the solvent acetonitrile at room temperature. Then, Fe(btfa)3 and two hydroxyl groups of the substrates formed a five- or six-membered ring intermediate in the presence of the base. The subsequent reaction between the cyclic intermediate and a sulfonylation reagent led to the selective sulfonylation of the substrate. All key intermediates were captured in the high-resolution mass spectrometry assay, therefore demonstrating this mechanism for the first time.
- Dong, Hai,Liu, Yu,Lv, Jian,Zhu, Jia-Jia
-
p. 3307 - 3319
(2020/03/25)
-
- Selective Asymmetric Transfer Hydrogenation of α-Substituted Acetophenones with Bifunctional Oxo-Tethered Ruthenium(II) Catalysts
-
A practical method for the asymmetric transfer hydrogenation of α-substituted ketones was developed utilizing oxo-tethered N-sulfonyldiamine-ruthenium complexes. Reduction by HCO2H and HCO2K in a mixed solvent of EtOAc/H2O allowed for the selective synthesis of halohydrins from 2-bromoacetophenone (98%) and 2-chloroacetophenone (>99%), leading to suppressed undesired side reactions stemming from formylation under the typical reaction conditions using an azeotropic 5:2 mixture of HCO2H and Et3N. A range of functional groups, such as halogens, methoxy, nitro, dimethylamino, and ester groups, were well tolerated, highlighting the potential of this method. Nearly complete selectivity with a preferable ee was maintained even with a substrate/catalyst (S/C) ratio of 5000. This catalyst system was also effective for the asymmetric reduction of α-sulfonated ketones without eroding the leaving group. (Figure presented.).
- Yuki, Yamato,Touge, Taichiro,Nara, Hideki,Matsumura, Kazuhiko,Fujiwhara, Mitsuhiko,Kayaki, Yoshihito,Ikariya, Takao
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p. 568 - 574
(2017/12/13)
-
- Study on a New Method for Synthesis of Mirabegron
-
Mirabegron is a muscle relaxing drug for the treatment of overactive bladder. The existing synthetic methods for mirabegron produced intermediate product 4-(2-(phenethylamino)ethyl)aniline, which complicated the final product purification process. In this study, we designed a new synthetic route for mirabegron with low cost starting materials and a production of mirabegron at a 99.6% purity and a 61% overall yield. Particularly, this new synthetic route did not produce side product 4-(2-(phenethylamino)ethyl)aniline, which significantly simplified the product purification process.
- Xu, Guiqing,Mao, Shen,Mao, Longfei,Jiang, Yuqin,Zhou, Yong,Shen, Jiaxuan,Dong, Wenpei
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p. 2703 - 2707
(2017/09/26)
-
- Development of novel LP1-based analogues with enhanced delta opioid receptor profile
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Pain relief achieved by co-administration of drugs acting at different targets is more effective than that obtained with conventional MOR selective agonists usually associated to relevant side effects. It has been demonstrated that simultaneously targeting different opioid receptors is a more effective therapeutic strategy. Giving the promising role for DOR in pain management, novel LP1-based analogues with different N-substituents were designed and synthesized with the aim to improve DOR profile. For this purpose, we maintained the phenyl ring in the N-substituent of 6,7-benzomorphan scaffold linked to an ethyl spacer bearing a hydroxyl/methyl or methoxyl group at carbon 2 or including it in a 1,4-benzodioxane ring. LP1 analogues were tested by competition binding assays. Compounds 6 (KiMOR = 2.47 nM, KiDOR = 9.6 nM), 7 (KiMOR = 0.5 nM and KiDOR = 0.8 nM) and 9 (KiMOR = 1.08 nM, KiDOR = 6.6 nM) retained MOR affinity but displayed an improved DOR binding capacity as compared to LP1 (KiMOR = 0.83 nM, KiDOR = 29.1 nM). Moreover, GPI and MVD functional assays indicated that compounds 6 (IC50 = 49.2 and IC50 = 10.8 nM), 7 (IC50 = 9.9 and IC50 = 11.8 nM) and 9 (IC50 = 21.5 and IC50 = 4.4 nM) showed a MOR/DOR agonist profile, unlike LP1 that was a MOR agonist/DOR antagonist (IC50 = 1.9 and IC50 = 1240 nM). Measurements of their antinociceptive effect was evaluated by mice radiant tail flick test displaying for compounds 6, 7 and 9 ED50 values of 1.3, 1.0 and 0.9 mg/kg, i.p., respectively. Moreover, the antinociceptive effect of compound 9 was longer lasting with respect to LP1. In conclusion the N-substituent nature of compounds 6, 7 and 9 shifts the DOR profile of LP1 from antagonism to agonism.
- Pasquinucci, Lorella,Turnaturi, Rita,Prezzavento, Orazio,Arena, Emanuela,Aricò, Giuseppina,Georgoussi, Zafiroula,Parenti, Rosalba,Cantarella, Giuseppina,Parenti, Carmela
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p. 4745 - 4752
(2017/10/05)
-
- Norepinephrine alkaloids as antiplasmodial agents: Synthesis of syncarpamide and insight into the structure-activity relationships of its analogues as antiplasmodial agents
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Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum syncarpum (Rutaceae) exhibited promising antiplasmodial activities against Plasmodium falciparum with reported IC50 values of 2.04 μM (D6 clone), 3.06 μM (W2 clone) and observed by us 3.90 μM (3D7 clone) and 2.56 μM (K1 clone). In continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric dihydroxylation as a key step has been accomplished. In order to study structure-activity-relationship (SAR) in detail, a library of 55 compounds (3–57), which are analogues/homologues of syncarpamide 1 were synthesized by varying the substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or by varying the acid groups in the ester and/or amide side chain based on the natural product lead molecule and further assayed in vitro against 3D7 and K1 strains of P. falciparum to evaluate their antiplasmodial activities. In order to study the effect of position of functional groups on antiplasmodial activity profile, a regioisomer (S)-58 of syncarpamide 1 was synthesized however, it turned out to be inactive against both the strains. Two compounds, (S)-41 and its enantiomer, (R)-42 having 3,4,5-trimethoxy cinnamoyl groups as side chains showed better antiplasmodial activity with IC50 values of 3.16, 2.28 μM (3D7) and 1.78, 2.07 μM (K1), respectively than the natural product, syncarpamide 1. Three compounds (S)-13, (S)-17, (S)-21 exhibited antiplasmodial activities with IC50 values of 6.39, 6.82, 6.41 μM against 3D7 strain, 4.27, 7.26, 2.71 μM against K1 strain and with CC50 values of 147.72, 153.0, >200 μM respectively. The in vitro antiplasmodial activity data of synthesized library suggests that the electron density and possibility of resonance in both the ester and amide side chains increases the antiplasmodial activity as compared to the parent natural product 1. The natural product syncarpamide 1 and four analogues/homologues out of the synthesized library of 55, (S)-41, (R)-42, (S)-55 and (S)-57 were assayed in vivo assay against chloroquine-resistant P. yoelii (N-67) strain of Plasmodium. However, none of the five molecules, 1, (S)-41, (R)-42, (S)-55 and (S)-57 exhibited any promising in vivo antimalarial activity against P. yoelii (N-67) strain. Compounds 4, 6, 7 and 11 showed high cytotoxicities with CC50 values of 5.87, 5.08, 6.44 and 14.04 μM, respectively. Compound 6 was found to be the most cytotoxic as compared to the standard drug, podophyllotoxin whereas compounds 4 and 7 showed comparable cytotoxicities to podophyllotoxin.
- Aratikatla, Eswar K.,Valkute, Tushar R.,Puri, Sunil K.,Srivastava, Kumkum,Bhattacharya, Asish K.
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supporting information
p. 1089 - 1105
(2017/08/03)
-
- AMIDO THIADIAZOLE DERIVATIVES AS NADPH OXIDASE INHIBITORS
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The present invention is related to amino thiazole derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).
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Page/Page column 114
(2016/07/05)
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- Stereoselective β-Mannosylation by Neighboring-Group Participation
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The stereoselective synthesis of glycosidic bonds is the main challenge of oligosaccharide synthesis. Neighboring-group participation (NGP) of C2 acyl substituents can be used to provide 1,2-trans-glycosides. Recently, the application of NGP has been extended to the preparation of 1,2-cis-glycosides with the advent of C2 chiral auxiliaries. However, this methodology has been strictly limited to the synthesis of 1,2-cis-gluco-type sugars. Reported herein is the design and synthesis of novel mannosyl donors which provide 1,2-cis-mannosides by NGP of thioether auxiliaries. A key element in the design is the use of1C4locked mannuronic acid lactones to enable NGP of the C2 auxiliary. In addition to C2 participation a new mode of remote participation of the C4 benzyl group was identified and provides 1,2-cis-mannosides.
- Elferink, Hidde,Mensink, Rens A.,White, Paul B.,Boltje, Thomas J.
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supporting information
p. 11217 - 11220
(2016/10/13)
-
- 9-Hetero-10-boraanthracene-derived borinic acid catalysts for regioselective activation of polyols
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Heteraborinine-derived borinic acids serve as efficient catalysts for regioselective monofunctionalization of di- and polyols. Arylborinic acids of this type, wherein the B-OH group is incorporated into a 6π electron system, display both improved catalytic activity for functionalization of diols and enhanced stability towards air oxidation relative to the 'parent' diphenylborinic acid (Ph2BOH). These properties enable their applications at loadings as low as 0.1 mol% and without the need for a stabilizing precatalyst ligand (e.g., ethanolamine). Complexation studies, computation and kinetic data suggest that while the heteraborinine-derived borinic acids show significantly lower association constants with substrates than Ph2BOH, this effect is more than compensated for by the increased nucleophilicity of their tetracoordinate diol adducts.
- Dimitrijevic, Elena,Taylor, Mark S.
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p. 3298 - 3303
(2013/07/26)
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- Regioselective, borinic acid-catalyzed monoacylation, sulfonylation and alkylation of diols and carbohydrates: Expansion of substrate scope and mechanistic studies
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Synthetic and mechanistic aspects of the diarylborinic acid-catalyzed regioselective monofunctionalization of 1,2- and 1,3-diols are presented. Diarylborinic acid catalysis is shown to be an efficient and general method for monotosylation of pyranoside derivatives bearing three secondary hydroxyl groups (7 examples, 88% average yield). In addition, the scope of the selective acylation, sulfonylation, and alkylation is extended to 1,2- and 1,3-diols not derived from carbohydrates (28 examples); the efficiency, generality, and operational simplicity of this method are competitive with those of state-of-the-art protocols including the broadly applied organotin-catalyzed or -mediated reactions. Mechanistic details of the organoboron-catalyzed processes are explored using competition experiments, kinetics, and catalyst structure-activity relationships. These experiments are consistent with a mechanism in which a tetracoordinate borinate complex reacts with the electrophilic species in the turnover-limiting step of the catalytic cycle.
- Lee, Doris,Williamson, Caitlin L.,Chan, Lina,Taylor, Mark S.
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supporting information; experimental part
p. 8260 - 8267
(2012/07/14)
-
- Tandem SN2-Michael addition to vinylogous carbonates for the stereoselective construction of 2,3,3,5-tetrasubstituted tetrahydrofurans
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A stereoselective method for the synthesis of substituted tetrahydrofuran derivatives employing a tandem alkylation-Michael addition sequence to vinylogous carbonates is developed. The method could be used to synthesize THFs bearing tertiary ethers. Further, the method is extended to the synthesis of adjacent bis-THFs.
- Gharpure, Santosh J.,Reddy, S. Raja Bhushan
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scheme or table
p. 6093 - 6097
(2011/01/04)
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- Further improvements of the dibutyl tin oxide-catalyzed regioselective diol tosylation
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In this Letter, we report that selective monotosylation of a 1,2-diol is possible using only 0.1 mol % of Bu2SnO. More interestingly, we found that the corresponding tin acetal 3b gave faster conversions and more reproducible reaction times. Moreover, the loading of this catalyst could be as low as 0.05-0.005 mol %.
- Guillaume, Michel,Lang, Yolande
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experimental part
p. 579 - 582
(2010/04/02)
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- Synthesis of hybrid 1,2,3-triazolo-δ-lactams/lactones using Huisgen [3+2] cycloaddition 'click-chemistry' in water
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The synthesis of a new class of hybrid 1,2,3-triazozlo-δ-lactams/lactones has been achieved using the Huisgen [3+2] dipolar cycloaddition 'click-chemistry' reaction of various organic azides with an activated alkyne in water, followed by cyclization.
- Kumar, Indresh,Rana, Sravendra,Cho, Jae Whan,Rode, Chandrashekhar V.
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scheme or table
p. 352 - 355
(2010/06/16)
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- Substituted 1,2,3,4-tetrahydroquinolin-6-yloxypropanes as β3-adrenergic receptor agonists: Design, synthesis, biological evaluation and pharmacophore modeling
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In search of potent β3-adrenergic receptor agonists, a series of novel substituted 1,2,3,4-tetrahydroquinolin-6-yloxypropanes has been synthesized and evaluated for their β3-adrenergic receptor agonistic activity (ranging from -17.73% to 90.64% inhibition at 10 μM) using well established Human SK-N-MC neuroblastoma cells model. Four molecules viz. 11, 15, 22 and 23 showed β3-AR agonistic IC50 value of 0.55, 0.59, 1.18 and 1.76 μM, respectively. These four candidates have been identified as possible leads for further development of β3-adrenergic receptor agonists for obesity and Type-II diabetes pharmacotherapy. The free OH and NH functions are found to be essential for β3-adrenergic receptor agonistic activity. Among the synthesized β3-adrenergic receptor agonists having 1,2,3,4-tetrahydroquinoline scaffold, the N-benzyl group is found to be superior over N-arylsulfonyl group. A putative pharmacophore model has been modeled considering the above four active molecules which distinguishes well between the active and inactive molecules.
- Shakya, Neeraj,Roy, Kuldeep K.,Saxena, Anil K.
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supporting information; experimental part
p. 830 - 847
(2009/07/25)
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- Enantioselective synthesis of 1-arylethanediols by rhodium-catalyzed transfer hydrogenation of α-tosyloxyarylketones
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Catalytic transfer hydrogenation of α-tosyloxyarylketones mediated by a chiral rhodium complex using an azeotropic mixture of formic acid/triethylamine afforded the corresponding 1-arylethanediol monotosylates in excellent yield with high enantioselectivity.
- Lee, Do-Min,Kumaraswamy, Gullapalli,Lee, Kee-In
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experimental part
p. 73 - 78
(2010/03/26)
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- METHOD FOR THE PREPARATION OF OPTICALLY ACTIVE 2-SULFONYLOXY-1-PHENYLETHANOL DERIVATIVES
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Optically active 2-sulfonyloxy-1-phenylethanol derivative of formula (II) can be prepared easily and selectively by the method of the present invention using an asymmetric reduction of an α-sulfonyloxy acetophenone compound with a rhodium catalyst having petamethylcyclopentadienyl group and a hydrogen donor, and the compound of formula (II) obtained in the inventive method exhibits a higher e.e. (enantiomer excess) value than that of the products in the conventional methods.
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Page/Page column 9
(2008/12/05)
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- Design, synthesis, and structure-activity relationship of carbamate-tethered aryl propanoic acids as novel PPARα/γ dual agonists
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We have developed a new class of PPARα/γ dual agonists, which show excellent agonistic activity in PPARα/γ transactivation assay. In particular, (R)-9d was identified as a potent PPARα/γ dual agonist with EC50s of 0.377 μM in PPARα and 0.136 μM in PPARγ, respectively. Interestingly, the structure-activity relationship revealed that the stereochemistry of the identified PPARα/γ dual agonists significantly affects their agonistic activities in PPARα than in PPARγ.
- Kim, Nam-Jung,Lee, Kwang-Ok,Koo, Bon-Woong,Li, Funan,Yoo, Ja-Kyung,Park, Hyun-Ju,Min, Kyung-Hoon,Lim, Joong In,Kim, Mi Kyung,Kim, Jin-Kwan,Suh, Young-Ger
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p. 3595 - 3598
(2008/02/11)
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- Process for the preparation of enantiomerically pure 3-phenyl-3-hydroxypropylamine
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The present invention relates to an improved process for the synthesis of enantiomerically pure 3-phenyl-3-hydroxypropylamine of formula I; more particularly the present invention relates to the said process using styrene; the synthetic strategy features a Sharpless asymmetric dihydroxylation (SAD) route to the target compound, using styrene, a readily accessible starting material gives the optically pure dihydroxy compound (ee >97%; the selective monotosylation of primary alcohol, nucleophilic displacement by cyano and subsequent reduction to amino group furnishes the desired 3-phenyl-3-hydroxypropylamine in enatiomerically pure form, a key intermediate in the synthesis of variety of oxetine related anti-depressant drugs.
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- Catalytic regioselective sulfonylation of α-chelatable alcohols: Scope and mechanistic insight
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This paper describes a convenient protocol for the regioselective sulfonylation of α-chelatable alcohols. Typically, the reaction of α-heterosubstituted alcohols with 1 equiv of p-TsCl and 1 equiv of Et3N in the presence of 2 mol % of Bu2SnO leads to rapid, regioselective, and exclusive monotosylation. The pKa of the amine was correlated to the reaction rate. A plausible mechanism for this reaction has been proposed on the basis of 119Sn NMR studies.
- Martinelli, Michael J.,Vaidyanathan, Rajappa,Pawlak, Joseph M.,Nayyar, Naresh K.,Dhokte, Ulhas P.,Doecke, Christopher W.,Zollars, Lisa M. H.,Moher, Eric D.,Khau, Vien Van,Kosmrlj, Berta
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p. 3578 - 3585
(2007/10/03)
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- Naphthyloxy acetic acid derivatives and a pharmaceutical composition comprising them as an active ingredient
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The naphthyloxyacetic acid derivatives of the formula (I) wherein A is H, -(alkylene)COOR1, -(alkylene)CONR2R3, -(alkylene)OH, -(alkylene)tetrazole, -(alkylene)CN; E is single bond or alkylene; G is —S—, —SO—, —SO2—, —O— or —NR4—; L is alkylene, —(CH2)m—CH═CH—(CH2)n— or —(CH2)x—CH(OH)—(CH2)y—; M is phenyl, phenyl(thio, oxy, amino), diphenylmethyl, diphenylmethyl(thio, oxy, amino), and pharmaceutical composition comprising them as an active ingradient. The compounds of the formula (I) can combine PGE2receptor and exhibit the activity to antagonize or agonize for PGE2receptor. Therefore, they are useful as anti-hyperlipemia, for the prevention of abortion, for analgesics, as antidiarrheals, sleep inducer, diuretic, anti-diabetes, abortient, cathartics, antiulcer, anti-gastritis or antihypertensive etc.
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-
Referential example 7
(2010/11/29)
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- Rhodium versus ruthenium: Contrasting behaviour in the asymmetric transfer hydrogenation of α-substituted acetophenones
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The reduction of a number of α-substituted acetophenones has been achieved using both ruthenium(II)- and rhodium(III)-based asymmetric transfer hydrogenation catalysts employing formic acid as the hydrogen donor.
- Cross, David J.,Kenny, Jennifer A.,Houson, Ian,Campbell, Lynne,Walsgrove, Tim,Wills, Martin
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p. 1801 - 1806
(2007/10/03)
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- Selective sulfonylation of 1,2-diols and derivatives catalyzed by a recoverable fluorous tin oxide
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Fluorous tin oxide (C6F13CH2CH2)2SnO is readily synthesized, exhibits spectra that are generally similar to dibutyltin oxide and appears to exist as an oligomer or polymer. The fluorous tin oxide can be used catalytically to effect the selective monotosylation of 1,2-diols with TsCl/Et3N, and it can be readily recovered and reused. (C) 2000 Published by Elsevier Science Ltd.
- Bucher,Curran
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p. 9617 - 9621
(2007/10/03)
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- Dibutyltin oxide catalyzed selective sulfonylation of α-chelatable primary alcohols
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(equation presented) The reaction of substituted glycols with catalytic dibutyltin oxide, stoichiometric p-toluenesulfonyl chloride, and triethylamine in CH2Cl2 resulted in the complete and rapid sulfonylation at the primary alcohol. The α-heterosubstituted primary alcohol moiety appeared optimal for best results, supporting the intermediacy of a five-membered chelate. The role of the amine is discussed, in addition to catalyst requirements and solvent effects.
- Martinelli, Michael J.,Nayyar, Naresh K.,Moher, Eric D.,Dhokte, Ulhas P.,Pawlak, Joseph M.,Vaidyanathan, Rajappa
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p. 447 - 450
(2008/02/11)
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- A New Stereochemical Model from NMR for Benzoylated Cyclodextrins, Promising New Chiral Solvating Agents for the Chiral Analysis of 3,5-Dinitrophenyl Derivatives
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Hexakis(2,3-di-O-benzoyl)-α-cyclodextrin and hexakis(2,3,6-tri-O-benzoyl)-α-cyclodextrin have been employed as chiral solvating agents (CSAs) for the NMR determination of the enantiomeric composition of derivatives of chiral amines, amino alcohols, alcohols, carboxyl acids, and amino acids bearing a 3,5-dinitrophenyl moiety. The conformational features of the two cyclodextrins have been carefully analyzed by NMR spectroscopy, and the origin of the symmetry change (C6 → C3), detected by NMR for hexakis(2,3-di-O-benzoyl)-α-cyclodextrin in CDC13, has been clarified.
- Uccello-Barretta, Gloria,Cuzzola, Angela,Balzano, Federica,Menicagli, Rita,Iuliano, Anna,Salvadori, Piero
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p. 827 - 835
(2007/10/03)
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- An external chiral ligand controlled enantioselective opening of oxirane and oxetane by organolithiums
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Enantioselective nucleophilic opening reactions of cyclohexene oxide and 3-phenyloxetane were achieved by the combination of an external chiral ligand and organolithiums in the presence of boran trifluoride to give the corresponding alcohols in up to 47% ee.
- Mizuno, Masashi,Kanai, Motomu,Iida, Akira,Tomioka, Kiyoshi
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p. 10699 - 10708
(2007/10/03)
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- Optically active N-1-phenylethyl derivatives of (1R)-2-amino-1-phenylethanol as chiral auxiliaries in the enantioselective addition of diethylzinc to arylaldehydes
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The aminoalcohols (1R)-2-N[(R)-1-phenylethyl]amino-1-phenylethanol, (1R)-2-N[(S)-1-phenylethyl]amino-1-phenylethanol, and (1R)-2-N-methyl-N[(R)-1-phenylethyl]amino-1-phenylethanol, synthesized by simple procedures, have been used as chiral catalysts in the enantioselective addition of diethylzinc to arylaldehydes, obtaining optically active 1-arylpropanols in good chemical yields (47 to 95%) and e.e.s. up to 88%.
- Iuliano,Pini,Salvadori
-
p. 739 - 744
(2007/10/02)
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- A CHEMOENZYMATIC ACCESS TO OPTICALLY ACTIVE 1,2-EPOXIDES
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Lipase-catalyzed transacylation in organic media was employed to produce optically active α-hydroxy tosylate which could be readily converted to the corresponding 1,2-epoxides with high optical purity.
- Chen, Ching-Shih,Liu, Yeuk-Chuen
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p. 7165 - 7168
(2007/10/02)
-
- Stereochemical Aspects of Conjugation Reactions Catalyzed by Rat Liver Glutathione S-Transferase Isozymes
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Substrate enantioselectivity in the conjugation of phenethyl halides catalyzed by the glutathione S-transferases was studied with partially purified isozymes from rat liver.All of the isozymes tested possessed measurable activity with phenethyl chloride.Transferase A was the most active isozyme tested.Each of the isozymes demonstrated a high degree of substrate enantioselectivity, with transferase A being the most enantioselective isozyme.The enantioselectivity was determined by high-pressure liquid chromatographic analysis of the enzymatically formed diastereomeric products.The effect of limiting glutathione concentrations on the stereochemical outcome of the transferase A catalyzed conjugation of the chiral substrate, (S)-phenethyl chloride (4mM), was investigated.The stereochemical course of the enzymatic reaction was not significantly altered at glutathione concentrations as low as 25 μM.The major product of conjugation had the opposite stereochemistry at the benzylic carbon, indicating that the reaction proceeded primarily with inversion of configuration.The glutathione conjugates, S-glutathione, S-glutathione, S-benzylglutathione, and S-methylglutathione were studied as inhibitors of the transferase A catalysed conjugation of 1-chloro-2,4-dinitrobenzene.The order of the inhibitory potency was S-glutathione = S-benzylglutathione > S-glutathione > S-methylglutathione.This represented the first demonstration of the stereoselective product inhibition of the glutathione S-transferases.
- Mangold, James B.,Abdel-Monem, Mahmoud M.
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- Phenethanolamines, compositions containing the same, and method for effecting weight control
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Optically active N-3-(4-substituted phenyl)propyl-β-phenethanolamines are provided as well as pharmaceutical compositions containing such compounds. A method for effecting weight control in obese animals utilizing optically active phenethanolamines is disclosed. Novel intermediates useful in the preparation of optically active β-phenethanolamines are provided.
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