1606-47-9Relevant articles and documents
Brown,Johnson
, p. 4706 (1962)
Ruthenium-lewis acid catalyzed asymmetric diels-alder reactions between dienes and α,β-unsaturated ketones
Rickerby, Jenny,Vallet, Martial,Bernardinelli, Gerald,Viton, Florian,Kuendig, E. Peter
, p. 3354 - 3368 (2008/03/27)
The complex [Ru(Cp)(R,R-BIPHOP-F)(acetone)][SbF6],(R,R)-1a. was used as catalyst for asymmetric Diels-Alder reactions between dienes (cyclopentadiene, methylcyclopentadienc, isoprene, 2,3-dimethylbutadiene) and α,β-unsaturated ketones (methyl vinyl ketone (MVK). ethyl vinyl ketone, divinyl ketone, α-bromovinyl methyl ketone and α-chlorovinyl methyl ketone). The cycloaddition products were obtained in yields of 50-_90% and with enantioselectivities up to 96% ee. Ethyl vinyl ketone, divinyl ketone and the halogenated vinyl ketones worked best and their reactions with acyclic dienes consistently provided products with >90% ee. α-Chlorovinyl methyl ketone performed better than α-bromovinyl methyl ketone. The reaction also provided a [4.3.1]bicyclic ring system in 95% ee through an intramolecular cycloaddition reaction. Crystal structure determinations of [Ru(Cp)((S,S)-BIPHOP-F)(mvk)]-[SbF6], (S,S)-1b, and [Ru(Cp)((R,R)-Me4BIPHOP-F)(acrolein)][SbF6], (R,R)-2b, provided the basis for a rationalization of the asymmetric induction.
Dissociated nonsteroidal glucocorticoid receptor modulators; discovery of the agonist trigger in a tetrahydronaphthalene-benzoxazine series
Barker, Mike,Clackers, Margaret,Copley, Royston,Demaine, Derek A.,Humphreys, Davina,Inglis, Graham G. A.,Johnston, Michael J.,Jones, Haydn T.,Haase, Michael V.,House, David,Loiseau, Richard,Nisbet, Lesley,Pacquet, Francois,Skone, Philip A.,Shanahan, Stephen E.,Tape, Dan,Vinader, Victoria M.,Washington, Melanie,Uings, Iain,Upton, Richard,McLay, Iain M.,Macdonald, Simon J. F.
, p. 4216 - 4231 (2007/10/03)
The tetrahydronaphthalene-benzoxazine glucocorticoid receptor (GR) partial agonist 4b was optimized to produce potent full agonists of GR. Aromatic ring substitution of the tetrahydronaphthalene leads to weak GR antagonists. Discovery of an "agonist trigger" substituent on the saturated ring of the tetrahydronaphthalene leads to increased potency and efficacious GR agonism. These compounds are efficacy selective in an NFkB GR agonist assay (representing transrepression effects) over an MMTV GR agonist assay (representing transactivation effects). 52 and 60 have NFkB pIC50 = 8.92 (105%) and 8.69 (92%) and MMTV pEC50 = 8.20 (47%) and 7.75 (39%), respectively. The impact of the trigger substituent on agonism is modeled within GR and discussed. 36, 52, and 60 have anti-inflammatory activity in a mouse model of inflammation after topical dosing with 52 and 60, having an effect similar to that of dexamethasone. The original lead was discovered by a manual agreement docking method, and automation of this method is also described.
