- Sassafras oil, carrot bits and microwaves: Green lessons learned from the formal total synthesis of (-)-talampanel
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A formal total synthesis of (-)-talampanel (1), a 2,3-benzodiazepine is described. This work was undertaken to utilize greener reaction conditions. Safrole (a renewable source) was converted to (1) in eight steps, including an enantioselective bioreduction using carrots as the key step. Microwave irradiation was also used to perform three reaction steps.
- Omori, Alvaro Takeo,De Oliveira, Camila De Souza,Andrade, Kleber Tellini,Capeletto, Marina Gon?alves
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p. 103563 - 103565
(2015/12/23)
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- Chemoenzymatic synthesis of enantiomerically pure syn-configured 1-aryl-3-methylisochroman derivatives
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A two-step synthesis of various enantiomerically pure 1-aryl-3- methylisochroman derivatives was accomplished through asymmetric biocatalytic ketone reduction followed by an oxa-Pictet-Spengler reaction. The compounds were obtained in good to excellent yield (47-92 %) in favor of the syn diastereomers [dr (syn/anti) up to 99:1]. Enantiopure arylpropanols serving as pronucleophiles for the C-C bond-formation step were obtained by biocatalytic reduction by employing enantiocomplementary alcohol dehydrogenases, which gave access to the (S) and (R) enantiomer with up to >99 % conversion and up to >99 % ee. A two-step sequence involving a biocatalytic hydrogen-transfer reduction and a syn-diastereoselective oxa-Pictet-Spengler reaction was established to provide a series of 1-aryl-3-methylchroman derivatives with perfect enantioselectivity; PTSA = para-toluenesulfonic acid. Copyright
- Simon, Robert C.,Busto, Eduardo,Richter, Nina,Belaj, Ferdinand,Kroutil, Wolfgang
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p. 111 - 121
(2014/01/06)
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- Organocatalytic approach to (s)-1-arylpropan-2-ols: Enantioselective synthesis of the key intermediate of antiepileptic agent (-)-talampanel
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An efficient organocatalytic route for the preparation of enantioselective synthesis of (S)-1-arylpropan-2-ols derivatives, including the key intermediate of antiepileptic agent (-)-talampanel is described. The key steps involved are L-proline-catalyzed a
- Sawant, Rajiv T.,Waghmode, Suresh B.
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experimental part
p. 2269 - 2277
(2010/09/11)
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- Enantioselective, ketoreductase-based entry into pharmaceutical building blocks: Ethanol as tunable nicotinamide reductant
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(Chemical Equation Presented) The use of NADH- and NADPH-dependent ketoreductases to access enantioenriched pharmaceutical building blocks is reported. Seven structurally diverse synthons are obtained, including those for atomoxetine (KRED 132), talampanel (RSt-ADH and CPADH), Dolastatin (KRED 132), and fluoxetine (KRED 108/132). Ethanol may be used as stoichiometric reductant, regenerating both nicotinamide cofactors, particularly under four-electron redox conditions. Its favorable thermodynamic and economic profile, coupled with its advantageous dual cosolvent role, suggests a new application for biomass-derived ethanol.
- Broussy, Sylvain,Cheloha, Ross W.,Berkowitz, David B.
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supporting information; experimental part
p. 305 - 308
(2009/07/18)
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- Kinetic and chemical resolution of different 1-phenyl-2-propanol derivatives
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Seven chiral target molecules containing a hydroxy group have been resolved by both biocatalytic and chemical means. The lipase-catalyzed acylation mainly yielded the acylated derivative of the (R)-alcohols with moderate enantiomeric excess and the enantiopure (S)-alcohols. In the course of the chemical resolution, first the dicarboxylic acid monoesters of the target molecules were synthesized and the resolution of these monoesters was attempted by different homochiral bases. By re-resolution and/or optimization of the reaction time and/or recrystallization, respectively, each molecule was produced in very high enantiomeric purity.
- Kiss, Violetta,Egri, Gabriella,Balint, Jozsef,Ling, Istvan,Barkoczi, Jozsef,Fogassy, Elemer
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p. 2220 - 2234
(2007/10/03)
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- Stereoselective production of (S)-1-aralkyl- and 1-arylethanols by freshly harvested and lyophilized yeast cells
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Substituted (S)-1-phenyl- 2a-h and (S)-1-benzyl-propan-2-ols 4a and b, and (S)-1-phenylethanol 6 were produced from prochiral ketones 1a-h, 3a,b and 5 by reductions with freshly harvested Zygosaccharomyces rouxii and Debaryomyces hansenii cells. The bioreductions were also performed by lyophilized cells. Comparison of the secondary alcohols from the bioreductions 2b-e,g,h and 4a and authentic (S)-alcohols (S)-2b-e,g,h and (S)-4a synthesized from enantiopure (S)-methyloxirane 7 proved the absolute configuration of the products.
- Erdelyi, Balazs,Szabo, Antal,Seres, Gabor,Birincsik, Laszlo,Ivanics, Jozsef,Szatzker, Gabor,Poppe, Laszlo
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p. 268 - 274
(2007/10/03)
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- Amano PS-catalysed enantioselective acylation of (±)-α-methyl-1,3-benzodioxole-5-ethanol: An efficient resolution of chiral intermediates of the remarkable antiepileptic drug candidate, (-)-talampanel
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(S)-(+)-α-Methyl-1,3-benzodioxole-5-ethanol 5 is a chiral building block in the synthesis of the future drug (-)-talampanel 1. Amano PS-induced enantioselective acylation of (±)-3 at 50°C using vinyl acetate as acyl donor furnished (+)-5 in 53% yield and
- Easwar, Srinivasan,Argade, Narshinha P.
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p. 333 - 337
(2007/10/03)
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- Crystalline form of dihydro-2,3-benzodiazepine derivative
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A physical form of (R)-7-acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine having an X-ray powder diffraction pattern with d spacings at 12.78, 9.48, 8.99, 8.64, 8.23, 6.39, 6.27. 5.73, 4.01 and 3.96 ?. The compound is
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- Physical form of dihydro-2,3-benzodiazepine derivative
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A physical form of (R)-7-acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine having an X-ray powder diffraction pattern with d spacings at 10.61, 8.83, 6.78, 5.83, 4.13 and 3.74 ?. The compound is useful as an AMPA antag
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- Dihydro-2,3-benzodiazepine derivatives
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Compounds having general formula (I) wherein R is hydrogen or C1 -C10 alkyl; X is an aromatic moiety selected from phenyl, thienyl, furyl, pyridyl, imidazolyl, benzimidazolyl, benzothiazolyl and phthalazinyl which is unsubstituted or
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- STEREOSELECTIVE PROCESS FOR PRODUCING DIHYDRO-2,3-BENZODIAZEPINE DERIVATIVES
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A process for stereoselectively forming N-substituted dihydro-2,3 benzodiazepines which are useful as AMPA receptor antagonists. The process includes an opening reduction step which sets the stereochemistry of the intermediates and the final compounds to
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