- Quaternary Charge-Transfer Complex Enables Photoenzymatic Intermolecular Hydroalkylation of Olefins
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Intermolecular C-C bond-forming reactions are underdeveloped transformations in the field of biocatalysis. Here we report a photoenzymatic intermolecular hydroalkylation of olefins catalyzed by flavin-dependent 'ene'-reductases. Radical initiation occurs via photoexcitation of a rare high-order enzyme-templated charge-transfer complex that forms between an alkene, α-chloroamide, and flavin hydroquinone. This unique mechanism ensures that radical formation only occurs when both substrates are present within the protein active site. This active site can control the radical terminating hydrogen atom transfer, enabling the synthesis of enantioenriched γ-stereogenic amides. This work highlights the potential for photoenzymatic catalysis to enable new biocatalytic transformations via previously unknown electron transfer mechanisms.
- Page, Claire G.,Cooper, Simon J.,Dehovitz, Jacob S.,Oblinsky, Daniel G.,Biegasiewicz, Kyle F.,Antropow, Alyssa H.,Armbrust, Kurt W.,Ellis, J. Michael,Hamann, Lawrence G.,Horn, Evan J.,Oberg, Kevin M.,Scholes, Gregory D.,Hyster, Todd K.
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supporting information
p. 97 - 102
(2021/01/12)
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- Preparation method of intermediate of synthesis of pilsicainide hydrochloride
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The invention provides a preparation method of an intermediate for synthesis of pilsicainide hydrochloride. The method comprises the following steps: step 1, performing a polymerization reaction on butyrolactam (I) and gamma-butyrolactone (II) under strong base and predetermined conditions to form N-(3-carboxypropyl)butyrolactam (III); step 2, performing cyclization on the N-(3-carboxypropyl)butyrolactam(III) at a high temperature in a monoisopropyl malonate solvent, performing condensation on the cyclization product and a monoester malonate to form 7alpha-pyrrolizine-acetate, wherein preferred choice is to produce 7alpha-pyrrolizine-isopropyl acetate (V); and step 3, performing hydrolysis on the 7alpha-pyrrolizine-acetate in an acid to form the corresponding pharmaceutically-acceptable salt. The preparation method provided by the invention avoids expensive or difficult-to-obtain raw materials, avoids use of liquid ammonia in the synthetic process, reduces the reaction steps, and has simple operation, less three waste (waste water, waste gas and solid waste) and a high yield.
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Paragraph 0043-0051
(2019/07/11)
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- Synthesis of an azabicyclic framework towards (±)-actinophyllic acid
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Lewis acid mediated intramolecular Mannich reaction between an azocinone and a 3-formylindole was investigated as part of a study towards the synthesis of actinophyllic acid. The intramolecular Mannich reaction resulted in a single diastereomer of the 1-azabicyclo[4.2.1]nonan-5-one core framework, although single crystal X-ray structure analysis revealed that this had the undesired stereochemistry in comparison with the natural product.
- Mortimer, Danny,Whiting, Matthew,Harrity, Joseph P.A.,Jones, Simon,Coldham, Iain
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p. 1255 - 1257
(2014/02/14)
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- Pilsicainide and its oxymethylene analog: Facile alternative syntheses and in vitro testing on human skeletal muscle sodium channels
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Facile, alternative synthetic routes gave access to both pilsicainide [N-(2,6-dimethylphenyl)-2-tetrahydro-lH-pyrrolizin-7a(5H)-ylacetamide, 1], a well-known Ic antiarrhythmic drug, and its oxymethylene analog 2. Both compounds were tested on human skeletal muscle voltage-gated sodium channels, hNavl.4, transfected in tsA201 cells. 7a-[2-(2,6-Dimethylphenoxy)ethyl]hexahydro-lH-pyrrolizine (2) behaved as a bioisostere of 1, exerting a 4-fold more potent use-dependent block.
- Bruno, Claudio,Catalano, Alessia,Desaphy, Jean-Francois,Cavalluzzi, Maria M.,Carocci, Alessia,Dipalma, Antonella,Franchini, Carlo,Lentini, Giovanni,Camerino, Diana Conte,Tortorella, Vincenzo
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p. 2011 - 2026
(2008/09/18)
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- Synthesis of Δ1- and/or Δ8-Dehydroindolizidines and Related Compounds
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A facile synthesis of Δ1- and/or Δ8-dehydroindolizidine and related compounds, consisting of dry distillation of γ-(N-2-piperidinonyl)butyric acid over soda-lime, is described.Reductions of these dehydroindolizidines and stereochemistry of 1-methylindolizidine are also described.
- Miyano, Seiji,Fujii, Shinichiro,Yamashita, Osamu,Toraishi, Naoko,Sumoto, Kunihiro
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p. 1465 - 1468
(2007/10/02)
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