- MACROCYCLIC COMPOUNDS AND THEIR USE IN THE TREATMENT OF DISEASE
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The invention relates to heterocyclic compounds of the formula (I), in which all of the variables are as defined in the specification; capable of modulating the activity of CFTR. The invention further provides a method for manufacturing compounds of the invention, and its therapeutic uses. The invention further provides methods to their preparation, to their medical use, in particular to their use in the treatment and management of diseases or disorders including Cystic fibrosis and related disorders.
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Page/Page column 63; 64
(2020/07/14)
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- Phosphite-thioether/selenoether Ligands from Carbohydrates: An Easily Accessible Ligand Library for the Asymmetric Hydrogenation of Functionalized and Unfunctionalized Olefins
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A large family of phosphite-thioether/selenoether ligands has been easily prepared from accessible L-(+)-tartaric acid and D-(+)-mannitol and applied in the M-catalyzed (M=Ir, Rh) asymmetric hydrogenation of a broad number of substrates (46 in total). Its highly modular architecture has been crucial to maximize the catalytic performance. Improving most of the reported approaches, this ligand family presents a broad substrate scope. By selecting the ligand parameters high enantioselectivities (ee's up to 99 %) have therefore been achieved in a broad range of both, functionalized and unfunctionalized substrates. Interestingly, both enantiomers of the hydrogenation products can be usually achieved by changing the ligand parameters.
- Margalef, Jèssica,Borràs, Carlota,Alegre, Sabina,Alberico, Elisabetta,Pàmies, Oscar,Diéguez, Montserrat
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p. 2142 - 2168
(2019/04/13)
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- Rapid and scalable synthesis of chiral bromolactones as precursors to α-exo-methylene-γ-butyrolactone-containing sesquiterpene lactones
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The sesquiterpene lactones cover a diverse and pharmacologically important diversity space. In particular, the electrophilic α-exo-methylene-γ-butyrolactone moiety that is preponderant in this natural product family has been shown to readily engage in cov
- Lagoutte, Roman,Pastor, Miryam,Berthet, Mathéo,Winssinger, Nicolas
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supporting information
p. 6012 - 6021
(2018/09/11)
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- Phosphite-Thiother Ligands Derived from Carbohydrates allow the Enantioswitchable Hydrogenation of Cyclic β-Enamides by using either Rh or Ir Catalysts
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Phosphite-thioether ligands with a simple modular architecture, derived from inexpensive l-(+)-tartaric acid and d-mannitol, have been for the first time successfully applied (ee values up to 99 %) in the synthesis of 2-aminotetralines and 3-aminochromane
- Margalef, Jèssica,Pàmies, Oscar,Diéguez, Montserrat
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p. 813 - 822
(2017/02/05)
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- Synthesis of diacylglycerol analogs bearing photoaffinity tags for labelling mammalian diacylglycerol kinase
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Signaling lipids such as diacylglycerol (DAG), phosphatidic acid, and the phosphatidylinositol polyphosphates are site-specific ligands for protein binding partners. Herein, we report the apotheoses of our initial approach to the development of diverse probes which are vital for understanding lipid-protein interactions. When incorporated into liposomes, these probes reduce mammalian diacylglycerol kinase's (DGK) enzymatic activity in a concentration, time, and light dependent manner. This journal is
- Eni, Sammy Eni,Rowland, Meng,Best, Michael D.
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p. 25457 - 25461
(2015/03/30)
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- Versicolactones A and B: Total synthesis and structure revision
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To further determine absolute configurations of versicolactones A and B, total synthesis of versicolactones A and B and their six stereoisomers were reported in this Letter. The 1H and 13C NMR spectra of the synthetic erythro-stereoisomers matched perfectly with those of the natural products. Combined with the comparison of the specific rotations, the absolute configuration of versicolactones A and B were revised as (4Z,6R,7S)- and (4E,6R,7S)- from the corresponding (4Z,6R,7R)- and (4E,6R,7R)-6,7-dihydroxyocta- 2,4-dien-4-lactone, respectively.
- Wang, Liping,Zhu, Weiming
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p. 6729 - 6731
(2013/11/19)
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- AMPHIPHILIC COMPOUNDS AND SELF-ASSEMBLING COMPOSITIONS MADE THEREFROM
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The present disclosure relates to amphiphilic compounds, self assembling compositions formed from the amphiphilic compounds and methods of making such compositions.
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- Intramolecular Huisgen [3+2] cycloaddition in water: Synthesis of fused pyrrolidine-triazoles
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The intramolecular alkyne-azide Huisgen [3+2] cycloaddition reaction as a 'click-chemistry' reaction without a metal catalyst has been studied under aerobic conditions. The synthesis of various pyrrolidine-triazole hybrid compounds has also been achieved
- Kumar, Indresh,Mir, Nisar A.,Rode, Chandrashaker V.,Wakhloo, Basant P.
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experimental part
p. 225 - 229
(2012/06/18)
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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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- Total synthesis of (+)-varitriol
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The total synthesis of natural (+)-varitriol (1) was accomplished by starting from dimethyl L-tartrate. The key features were a substrate selective and diastereoselective PdII-catalysed bicyclisation of unsaturated protected triol 9 followed by regioselective ring-opening of bicyclic skeleton 10. The absolute configuration of the target was confirmed by single-crystal X-ray analysis for the first time.
- Palik, Miroslav,Karlubikova, OL'Ga,Lasikova, Angelika,Kozisek, Jozef,Gracza, Tibor
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scheme or table
p. 709 - 715
(2009/07/19)
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- Enantiomerically pure 4-amino-1,2,3-trihydroxybutylphosphonic acids
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(1S,2R,3S)-, (1R,2R,3S)- and (1S,2R,3R)-4-amino-1,2,3- trihydroxybutylphosphonic acids were synthesised. The synthetic strategy involved preparation of the respective 4-azido-2,3-O-isopropylidene-l-threose or -d-erythrose, addition of dialkyl phosphites, separation of C-1 epimeric O,O-dibenzyl phosphonates, the reduction of azides and the removal of the protecting groups. The (2R,3S) and (2R,3R) configurations in the final products were secured by employing diethyl l-tartrate and d-isoascorbic acid as starting materials. The stereochemical course of the addition to the carbonyl groups in 4-azido-2,3-O-isopropylidene-l-threose or -d-erythrose followed that established earlier for 2,3-O-isopropylidene-d-glyceraldehyde and similar (3:1-4:1) diastereoselectivities were achieved.
- Wróblewski, Andrzej E.,G?owacka, Iwona E.
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p. 11930 - 11938
(2007/10/03)
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- A convergent total synthesis of pumiliotoxins A and B via palladium-catalyzed cross-coupling reaction of homoallylic organozinc compounds with vinyl iodides
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A versatile convergent approach for preparing the pumiliotoxin alkaloids has been developed employing a Pd(0)-catalyzed cross-coupling reaction between homoallylic organozincs and vinyl iodides, which led to the asymmetric total synthesis of (+)-pumilioto
- Kibayashi, Chihiro,Aoyagi, Sakae
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p. 229 - 233
(2007/10/03)
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- Silver(I) oxide mediated highly selective monotosylation of symmetrical diols. Application to the synthesis of polysubstituted cyclic ethers
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(Matrix Presented) The reaction of symmetrical diols and oligo(ethylene glycol)s with a stoichiometric amount of p-toluenesulfonyl chloride in the presence of silver(I) oxide and a catalytic amount of potassium iodide led selectively to the monotosylate derivatives in high yields. Polysubstituted cyclic ethers were obtained readily upon treatment of the corresponding diols with an excess of silver oxide. The high selectivity was explained on the basis of the difference in acidity between the two hydroxy groups, which undergo an intramolecular hydrogen bonding.
- Bouzide, Abderrahim,Sauve, Gilles
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p. 2329 - 2332
(2007/10/03)
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- Mixtures and compositions suitable for controlling Hylotrupes bajulus and Pyrrhidium sanguineum
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A mixture containing one stereoisomer of 3-hydroxyhexan-2-one and two stereoisomers of hexane-2,3-diol, especially (3R)-3-hydroxy-hexan-2-one, (2R,3R)-hexane-2,3-diol and/or (2R,3R)-hexane-2,3-diol and compositions containing them and the use of the mixture and of the compositions for controllingHylotrupes bajulusandPyrrhidium sanguineumby means of the monitoring, capture or mating disruption method are described.
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- Chiral γ-(tetrahydropyranyloxy)allylstannane: a new chiral reagent for the asymmetric synthesis of syn 1,2-diols
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(2R,3S)-3-Allyloxy-3,4,5,6-tetrahydro-2H-pyran-2-methanol was prepared in high yield from tri-O-acetyl-D-glucal, an easily available and cheap chiral source.The hydroxy group was protected as the t-butyldiphenylsilyl ether, and the allyl group was converted to the corresponding allyl stannane via formation of allyl carbanion and subsequent trapping with tributylstannyl chloride.The γ-alkoxy allyl stannane 1 bearing the (2R,3S)-2--3,4,5,6-tetrahydro-2H-pyran-3-yloxy auxiliary at the allyl terminus was prepared by this procedure.The reaction of 1 with aldehydes in the presence of AlCl3*OEt2 or AlCl3 gave the corresponding syn adducts 2 with high diastereoselectivities; the ratio of syn/anti > 97:3.The diastereomeric excess of the syn adducts 2, that is, the ratio 2/(2 + the (S,S) isomer of 2), varied from 85 to 94percent.Removal of the protecting group of 2 gave the (R,R) diols 3.The high diastereo- and enantioselectivity in the formation of the (R,R) isomer is accounted for by an anti S'E transition state 18. allylstannane / γ-alkoxyallylstannane / asymmetric synthesis / syn-1,2-diol / Lewis acid / allylstannane-aldehyde condensation / γ-(tetrahydropyranyloxy)allylstannane / anti S'E
- Kadota, Isao,Kobayashi, Katsumi,Okano, Hiroshi,Asao, Naoki,Yamamoto, Yoshinori
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p. 615 - 623
(2007/10/02)
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- Synthesis of (3R)-3-Hydroxy-2-hexanone, (2R,3R)-2,3-Hexanediol and (2S,3R)-2,3-Hexanediol, the Male Sex Pheromone of Hylotrupes bajulus and Pyrrhidium sanguineum (Cerambycidae)
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The following compounds were identified as male pheromone components of the longhorn beetles Hylotrupes bajulus and Pyrrhidium sanguineum: (3R)-3-hydroxy-2-hexanone , (2S,3R)-2,3-hexanediol and (2R,3R)-2,3-hexanediol .The syntheses of enantiomerically pure samples, enantiomeric separation by chiral gas chromatography and unambiguous structure assignment of the target compounds are described. - Key Words: Cerambycidae / Longhorn beetle / Pheromones / Ketones, α-hydroxy- / Hylotrupes bajulus / Pyrrhidium sanguineum
- Schroeder, Frank,Fettkoether, Regina,Noldt, Uwe,Dettner, Konrad,Koenig, Wilfried A.,Francke, Wittko
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p. 1211 - 1218
(2007/10/02)
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- Asymmetric Synthesis of Syn 1,2-Diols via the Reaction of Aldehydes with Chiral γ-(Tetrahydropyranyloxy)allylstannanes
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Asymmetric synthesis of syn 1,2-diols 3 has been accomplished via the reaction of the chiral γ-alkoxy-substituted allylstannane 1 with aldehydes in the presence of AlCl3 or AlCl3*OEt2, followed by a five-step operation to remove the chiral auxiliary.
- Yamamoto, Yoshinori,Kobayashi, Katsumi,Okano, Hiroshi,Kadota, Isao
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p. 7003 - 7005
(2007/10/02)
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- Synthesis and the Absolute Configuration of Panaxacol
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Panaxacol, a polyacetylene isolated from the callus of Panax ginseng, was synthesized from D-(-)-diethyl tartrate.The absolute configuration of panaxacol was determined to be 9R,10R.
- Fujimoto, Yasuo,Satoh, Mitsuru,Takeuchi, Naoki,Kirisawa, Makoto
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p. 1619 - 1622
(2007/10/02)
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- Syntheses of Unsaturated Trihydroxy C-18 Fatty Acids Isolated from Rice Plants Suffering from Rice Blast Disease
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Two trihydroxy unsaturated C-18 fatty acids isolated from rice plants as agents with activity against blast disease were synthesized from (+)-dimethyl tartrate.Keywords: methyl (9S,12S,13S)-trihydroxyoctadeca-10E,15Z-dienoate; methyl (9S,12S,13S)-trihydroxy-10E-octadecenoate; rice blast disease; fetal calf aorta; (+)-dimethyl tartrate; Wittig-Horner reaction
- Suemune, Hiroshi,Harabe, Tetsuji,Sakai, Kiyoshi
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p. 3632 - 3637
(2007/10/02)
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- Preparation of (4R,5S)-(5-methyl-2,2-dimethyl-1,3-dioxolane-4-ylmethyl)-phosphonium iodide. A synthetic approach to olguine: further model studies
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The enantiomerically pure title compound ((4R,5S)-(5-methyl-2,2-dimethyl-1,3-dioxolane-4-ylmethyl)-phosphonium iodide) has been synthesized starting from (R,R)-(+)-tartaric acid.The synthesis of an oliguine analog has been carried out.Attempts have been made to improve the stereoselectivity and yield of key steps.
- Valverde, Serafin,Herradon, Bernardo,Rabanal, Rosa M.,Martin-Lomas, Manuel
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p. 332 - 338
(2007/10/02)
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- The Stereochemistry of Organometallic Compounds. XXIII. Synthesis of a Chiral Diphosphinite (diphin) and Evaluation of its Use as a Ligand for Asymmetric Catalysis
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(+)-(3S,4S)-Tetrahydrofuran-3,4-diyl bis(diphenylphosphinite) has been synthesized and its efficiency as a ligand an asymmetric hydrogenation, hydrocyanation and hydroformylation compared with closely related diphosphine, diphosphinite and di
- Jackson, W. Roy,Lovel, Craig G.
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p. 2069 - 2075
(2007/10/02)
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