- Iron-Catalyzed Intermolecular Functionalization of Non-Activated Aliphatic C?H Bonds via Carbene Transfer
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The modification of strong Csp3?H bonds via iron carbene intermediates under mild reaction conditions has been an important challenge with attractive prospective in organic synthesis. In this work, we show the efficient combination of an electrophilic iron catalyst with a lithium Lewis acid for the functionalization of strong Csp3?H bonds of cyclic and linear alkanes by the activation of commercially available ethyl diazoacetate (EDA). The reaction proceeds with good yields, under mild reaction conditions (40 °C) and large excess of substrate is not needed. In addition, excellent activity is observed in the cyclopropanation of challenging aliphatic olefins. (Figure presented.).
- Rodríguez, Mònica,Font, Gemma,Nadal-Moradell, Joel,Hernán-Gómez, Alberto,Costas, Miquel
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supporting information
p. 5116 - 5123
(2020/10/06)
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- Synthesis and evaluation of colletoic acid core derivatives
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Cortisol homeostasis has been linked to the pathogenesis of metabolic syndrome (MetS), since it stimulates hepatic gluconeogenesis and adipogenesis. MetS is classified as a constellation of health conditions that increase the risk of type 2 diabetes and cardiovascular disease. Intracellular cortisol levels are regulated by 11β-hydroxysteroid dehydrogenase (type 1 and type 2) in a tissue dependent manner. The type 1 enzyme (11β-HSD1) is widely expressed in glucocorticoid targeted tissues and is responsible for the conversion of cortisone to the active cortisol. Local reduction of cortisol regeneration presents a potential strategy for MetS treatment. Recently we disclosed the total synthesis of (+)-colletoic acid as a potent 11β-HSD1 inhibitor. Herein, we describe our improved processing chemistry for the synthesis of the colletoic acid core to access a diverse number of derivatives for evaluation against 11β-HSD1. The Evan's chiral auxiliary was utilized to construct the acyclic precursor 12 to afford the acorane core 9 using a modified Heck reaction in excellent chemical yields. The colletoic acid core derivatives showed modest activity against 11β-HSD1 and will serve for further biological evaluation.
- Ling, Taotao,Gautam, Lekh Nath,Griffith, Elizabeth,Das, Sourav,Lang, Walter,Shadrick, William R.,Shelat, Anang,Lee, Richard,Rivas, Fatima
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supporting information
p. 126 - 132
(2016/02/05)
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- Microwave-assisted regioselective olefinations of cyclic mono- and di-ketones with a stabilized phosphorus ylide
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A number of cyclic mono- and di-ketones underwent regioselective olefination with (carbethoxyethylidene)triphenylphospharane under controlled microwave heating. The Wittig reaction of 4-substituted cyclohexanones or 1,2- and 1,4-cyclohexanediones with the ylide at 190 °C for 20 min in MeCN afforded the exocyclic olefins in >94:6 isomer ratios. On the other hand, the same reactions carried out at 230 °C for 20 min in the presence of 20 mol % DBU furnished the endocyclic olefins in >83:17 isomer ratios. The base-mediated isomerization of the exocyclic olefins into the endocyclic isomers was primarily driven by thermodynamic stability of the products and the effect of ring structures on deconjugation was examined.
- Wu, Jinlong,Li, Dan,Wu, Huafeng,Sun, Lijie,Dai, Wei-Min
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p. 4643 - 4650
(2007/10/03)
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- Highly regioselective Wittig reactions of cyclic ketones with a stabilized phosphorus ylide under controlled microwave heating
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Significant base and temperature effects on the Wittig reactions of cyclohexanones with (carbethoxymethylene)triphenylphosphorane under microwave irradiation were observed. For the Wittig reactions carried out in a domestic microwave oven under solvent-free conditions, the initially formed exo-olefin products isomerized into the thermodynamically more stable endo-olefins due to uncontrolled high reaction temperature. In sharp contrast, under controlled microwave heating, both exo- and endo-olefins have been selectively synthesized by accurately regulating the reaction temperature with or without a base.
- Wu, Jinlong,Wu, Huafeng,Wei, Shaoyong,Dai, Wei-Min
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p. 4401 - 4404
(2007/10/03)
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- Acid-promoted olefination of ketones by an iron(III) porphyrin complex
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(Matrix presented) The acid-promoted olefination of unactivated ketones with diazo reagents in the presence of triphenylphosphine can be catalyzed by the commercially available iron(III) porphyrin complex Fe(TPP)Cl. The reactions were effectively carried out under mild conditions in a one-pot fashion with the use of a stoichiometric diazo reagents and substoichiometric benzoic acid. Examples include aromatic, aliphatic, cyclic, and unsaturated ketones with ethyl diazoacetate or tert-butyl diazoacetate.
- Chen, Ying,Huang, Lingyu,Zhang, X. Peter
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p. 2493 - 2496
(2007/10/03)
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- Thallium trinitrate mediated oxidation of 3-alkenols: Ring contraction vs cyclization
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The reaction of a series of six-membered ring 3-alkenols with thallium trinitrate (TTN) in three different experimental conditions was studied. Either cyclization products or ring contraction products were obtained, depending on the structure of the substrate as well as the nature of the solvent. The reaction of a seven-membered ring 3-alkenol with TTN led to the ring contraction product exclusively.
- Ferraz, Helena M. C.,Longo Jr., Luiz S.,Zukerman-Schpector, Julio
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p. 3518 - 3521
(2007/10/03)
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- Identification of novel ligands for the Gabapentin binding site on the α2δ subunit of a calcium channel and their evaluation as anticonvulsant agents
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As part of a program to investigate the structure-activity relationships of Gabapentin (Neurontin), a number of alkylated analogues were synthesized and evaluated in vitro for binding to the Gabapentin binding site located on the α2δ subunit of
- Bryans, Justin S.,Davies, Natasha,Gee, Nicolas S.,Dissanayake, Visaka U. K.,Ratcliffe, Giles S.,Horwell, David C.,Kneen, Clare O.,Morrell, Andrew I.,Oles, Ryszard J.,O'Toole, John C.,Perkins, Gemma M.,Singh, Lakhbir,Suman-Chauhan, Nirmala,O'Neill, Jacqueline A.
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p. 1838 - 1845
(2007/10/03)
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- Investigation into the preferred conformation of Gabapentin for interaction with its binding site on the α2δ subunit of a calcium channel
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A series of conformationally restricted Gabapentin analogues has been synthesised and used to propose the preferred conformation of Gabapentin for it to bind to the α2δ subunit of a calcium channel.
- Bryans, Justin S.,Davies, Natasha,Gee, Nicolas S.,Horwell, David C.,Kneen, Clare O.,Morrell, Andrew I.,O'Neill, Jacqueline A.,Ratcliffe, Giles S.
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p. 2481 - 2484
(2007/10/03)
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- Synthesis and antiallergy activity of [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one derivatives. II. 6-Alkyl- and 6-cycloalkylalkyl derivatives
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A series of 6-alkyl- or 6-(cycloalkylalkyl)-[1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]pyr imidin-9(3H)-ones 1b-o was synthesized from the corresponding 1,3,4-thiadiazol-5-amines 3b-o and the antiallergic activities of the products were evaluated. Among the compounds 6-(2-cyclohexylethyl)-[1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5-d]p yrimidin-9(3H)-one 1h, whose X-ray crystallographic stereostructure is shown, was found to be a promising new antiallergic agent, which has low toxicity and dual activity as a leukotriene D4 receptor antagonist and as an orally active mast cell stabilizer.
- Yokohama,Miwa,Aibara,Fujiwara,Matsumoto,Nakayama,Iwamoto,Mori,Moroi,Tsukada,Isoda
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p. 2391 - 2398
(2007/10/02)
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- Enantioselective Wittig-Horner Reaction in the Solide State
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Wittig-Horner reactions in the solid state of the inclusion compound of 4-methyl- or 3,5-dimethylcyclohexanone and an optically active host compound with (carbethoxymethylene)triphenylphosphorane gave optically active 4-methyl- and 3,5-dimethyl-1-(carbeth
- Toda, Fumio,Akai, Hiroshi
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p. 3446 - 3447
(2007/10/02)
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- Deracemization by enantioselective dehydrohalogenation. Synthesis of optically active compounds bearing a chiral axis.
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This work describes the deracemization of 4-tert-butyl and 4-methylcyclohexylidene acetic acids bearing a chiral axis.Enantioselective dehydrohalogenation of prochiral species by chiral lithium amides allowed us to obtain e.e. as high as 82percent.A mecha
- Duhamel, L.,Ravard, A.,Plaquevent, J. C.,Ple, G.,Davoust, D.
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p. 787 - 797
(2007/10/02)
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- 4'-Methyl-β-mercapto-β,β-cyclopentamethylenepropionic acid vasopressin antagonists
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Vasopressin antagonists which have a 4'-methyl-β-mercapto-β,β-cyclopentamethylenepropionic acid group have vasopressin antagonist activity without substantial agonist activity. A species of the invention is [1-(4'-methyl-β-mercapto-β,β-cyclopentamethylenepropionic acid)-2-(O-ethyl)-D-tyrosine-4-valine-8-arginine]vasopressin.
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- SYNTHESIS OF CYCLOHEXYLALIPHATIC ACIDS AND THEIR PHARMACOLOGICAL PROPERTIES
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A series of substituted cyclohexylacetic acids I has been obtained by hydrogenation of the unsaturated analogues II and III.Esters of these analogues were prepared by the Horner-Wittig reaction of the corresponding cyclohexanones IV and/or 2-cyclohexenones V with triethyl phosphonoacetate.These esters were obtained in two isomeric forms (Z and E), differing in the double bond in the exo-position.The derivatives with a substituent in the 2-position exhibited a partial shift of the double bond to the cyclohexane ring; this shift was especially marked in the 2-phenyl derivative.With the acids I-III, activation of fibrinolysis was assessed by the hanging clot method; the anti-inflammatory effect was assessed by inhibition of two experimental model inflammations.The regression equation relating fibrinolytic capacity to lipophilicity was a quadratic one, the logarithm of optimum lipophilicity being log Popt = 5.55.A qualitative assessment of the anti-inflammatory effect in relation to lipophilicity suggests that log Popt is probably higher than with arylaliphatic acids.These acids seem to have an active site different from that of the acids I-III.
- Kuchar, Miroslav,Brunova, Bohumila,Grimova, Jaroslava,Vanecek, Stanislav,Holubek, Jiri
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p. 2896 - 2908
(2007/10/02)
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- ELECTRON TRANSFER FROM METAL SURFACES. FORMATION OF LITHIUM AND GRIGNARD REAGENTS.
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Chiral (+)-(S)-4-methylcyclohexylidenebromomethane (1) has been prepared from (-)-(R)-4-methylcyclohexylideneacetic acid by a stereospecific bromodecarboxylation reaction.The reaction was shown to proceed with an overall inversion of configuration.The rea
- Walborsky, H. M.,Banks, R. Bruce
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p. 849 - 868
(2007/10/02)
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