- Stereoselective synthesis of alicyclic ketones: A hydrogen borrowing approach
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A highly diastereoselective annulation strategy for the synthesis of alicyclic ketones from diols and pentamethylacetophenone is described. This process is mediated by a commercially available iridium(III) catalyst, and provides efficient access to a wide range of cyclopentane and cyclohexane products with high levels of stereoselectivity. The origins of diastereoselectivity in the annulation reaction have been explored by a series of control experiments, which provides an explanation for how each stereocentre around the newly forged ring is controlled.
- Armstrong, Roly J.,Akhtar, Wasim M.,Frost, James R.,Christensen, Kirsten E.,Stevenson, Neil G.,Donohoe, Timothy J.
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- Stereoselective Synthesis of Cyclohexanes via an Iridium Catalyzed (5 + 1) Annulation Strategy
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An iridium catalyzed method for the synthesis of functionalized cyclohexanes from methyl ketones and 1,5-diols is described. This process operates by two sequential hydrogen borrowing reactions, providing direct access to multisubstituted cyclic products with high levels of stereocontrol. This methodology represents a novel (5 + 1) strategy for the stereoselective construction of the cyclohexane core.
- Akhtar, Wasim M.,Armstrong, Roly J.,Frost, James R.,Stevenson, Neil G.,Donohoe, Timothy J.
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p. 11916 - 11920
(2018/09/27)
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- Structure-Based Design of β5c Selective Inhibitors of Human Constitutive Proteasomes
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This work reports the development of highly potent and selective inhibitors of the β5c catalytic activity of human constitutive proteasomes. The work describes the design principles, large hydrophobic P3 residue and small hydrophobic P1 residue, that led to the synthesis of a panel of peptide epoxyketones; their evaluation and the selection of the most promising compounds for further analyses. Structure-activity relationships detail how in a logical order the β1c/i, β2c/i, and β5i activities became resistant to inhibition as compounds were diversified stepwise. The most effective compounds were obtained as a mixture of cis- and trans-biscyclohexyl isomers, and enantioselective synthesis resolved this issue. Studies on yeast proteasome structures complexed with some of the compounds provide a rationale for the potency and specificity. Substitution of the N-terminus in the most potent compound for a more soluble equivalent led to a cell-permeable molecule that selectively and efficiently blocks β5c in cells expressing both constitutive proteasomes and immunoproteasomes.
- Xin, Bo-Tao,De Bruin, Gerjan,Huber, Eva M.,Besse, Andrej,Florea, Bogdan I.,Filippov, Dmitri V.,Van Der Marel, Gijsbert A.,Kisselev, Alexei F.,Van Der Stelt, Mario,Driessen, Christoph,Groll, Michael,Overkleeft, Herman S.
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p. 7177 - 7187
(2016/08/24)
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- PYRIMIDINE CYCLOHEXYL GLUCOCORTICOID RECEPTOR MODULATORS
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The present invention provides a class of pyrimidinedione cyclohexyl compounds and methods of using these compounds as glucocorticoid receptor modulators
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Page/Page column 35
(2012/10/08)
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- ARYL-CYCLOHEXYL-TETRAAZABENZO[E]AZULENES
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The present invention is concerned with aryl-cyclohexyl-tetraazabenzo[e]azulenes of formula I, wherein R1, R2 and R3 are as described herein. The compounds according to the invention act as Via receptor modulators, and in
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Page/Page column 40-41
(2011/10/13)
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- First structure-activity relationship study on dopamine D3 receptor agents with N-[4-(4-Arylpiperazin-1-yl)butyl]-arylcarboxamide structure
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Structure-affinity relationships of N-[4-(4-arylpiperazin-1-yl)butyl] arylcarboxamides as D3 receptor ligands have been well characterized but not structure-activity relationships. In a first attempt to clarify this issue, seven 1-(2,3-dichloro
- Leopoldo, Marcello,Lacivita, Enza,Colabufo, Nicola A.,Contino, Marialessandra,Berardi, Francesco,Perrone, Roberto
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p. 7919 - 7922
(2007/10/03)
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- THERAPEUTIC AGENT FOR DIABETES
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A therapeutic agent for diabetes, which comprises a compound of the formula [I] wherein Xis a group of the formula wherein R4and R5are the same or different and each is a hydrogen atom, an optionally substituted alkyl having 1 to 5 carbon atoms and the like, and R6is a hydrogen atom or an amino-protecting group; R1is an optionally substituted alkyl having 1 to 5 carbon atoms, an optionally substituted alkenyl having 2 to 6 carbon atoms and the like, R2is a hydrogen atom, an optionally substituted alkyl having 1 to 5 carbon atoms and the like, R2' is a hydrogen atom, and R3is an optionally substituted alkyl having 1 to 5 carbon atoms and the like, a prodrug thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof and a solvate thereof. The compound of the present invention shows superior blood sugar decreasing action on the state of hyperglycemia, but does not affect the blood sugar when it is in the normal range or in the hypoglycemic state, which means that it is free of serious side effects such as hypoglycemia. Therefore, the compound of the present invention is useful as a therapeutic drug for diabetes and also useful as a preventive of the chronic complications of diabetes.
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- LIQUID-CRYSTALLINE COMPOUNDS OF THE ALICYCLIC SERIES III. SYNTHESIS AND ISOMORPHISM OF ETHERS AND ESTERS CONTAINING THE PHENYLCYCLOHEXANE FRAGMENT
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A series of ethers and esters exhibiting mesomorphous characteristics were obtained from para-X-substituted trans-4-phenylcyclohexanols, trans-4-phenylcyclohexanecarboxylic acids (X = H, F, I, NO2, NH2, CN) and trans-1-hydroxymethyl-4-(p-cyanophenyl)cyclohexane.
- Karamysheva, L. A.,Torgova, S. I.,Agafonova, I. F.,Geivandov, R. Kh.,Bykova, V. V.,Burylin, P. A.
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p. 736 - 741
(2007/10/02)
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- Selective Photoelectrochemical Oxidation of Vicinal Cyclohexanedicarboxylic Acids: A Mechanistic Study
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The course of photooxidation of vicinal diacids on irradiated TiO2 suspensions proceeds via one-electron oxidative decarboxylation rather than two-electron oxidative bis-decarboxylation (which occurs on poised metal electrodes).The formation of a monocarboxylic acid as the major product indicates that trapping of an intermediate radical is competitive with further oxidation.The observed regiochemical preference in unsymmetrical diacids is rationalized by the conformational preference of the diacid adsorbed onto the photoactivated catalyst surface.
- Muzyka, Jennifer L.,Fox, Marye Anne
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p. 209 - 215
(2007/10/02)
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- STEREOSPECIFIC SYNTHESES AND REACTIONS OF ALLYL- AND ALLENYL-SILANES
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The stereospecifically anti synthesis of allyl- and allenyl-silanes by the reaction of a silylcuprate reagent with allyl and propargyl acetates is described.The SE2' reactions of these silanes with various electrophiles are shown to proceed wit
- Fleming, Ian,Terrett, Nicholas K.
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- SYNTHESIS OF TRANS-4-ALKYL-1-PHENYLCYCLOHEXANES AND THEIR DERIVATIVES
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The alkylation of benzene by 1-alkanoyl-2-chlorocyclohexanes and 1-alkanoyl-1-cyclohexenes leads to the formation of cis- and trans-4-alkanoyl-1-phenylcyclohexanes, the yields of which increase with increase in the reaction temperature. trans-4-Alkyl-1-phenylcyclohexanes were obtained from 4-alkanoyl-1-phenylcyclohexanes and also from the products from the reaction of 4-alkylcyclohexanones with phenylmagnesium bromide.Some mesomorphous derivatives of these hydrocarbons were synthesized.
- Bezborodov, V. S.,Bubel', O. N.,Konovalov, V. A.,Ptashnikov, Yu. L.
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p. 1479 - 1483
(2007/10/02)
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