6935-56-4Relevant academic research and scientific papers
SuperQuat 5,5-dimethyl-4-iso-propyloxazolidin-2-one as a mimic of Evans 4-tert-butyloxazolidin-2-one
Bull, Steven D.,Davies, Stephen G.,Garner, A. Christopher,Kruchinin, Dennis,Key, Min-Suk,Roberts, Paul M.,Savory, Edward D.,Smith, Andrew D.,Thomson, James E.
, p. 2945 - 2964 (2008/02/09)
The incorporation of a gem-dimethyl group at the 5-position of a chiral oxazolidinone biases the conformation of the adjacent C(4)-stereodirecting group such that the gem-dimethyl-4-iso-propyl combination mimics a C(4)-tert-butyl group, providing higher levels of stereocontrol than a simple 4-iso-propyloxazolidinone. The generality of this principle is demonstrated with applications in stereoselective enolate alkylations, kinetic resolutions, Diels-Alder cycloadditions and Pd-catalysed asymmetric acetalisation reactions. The Royal Society of Chemistry 2006.
Synthesis and pharmacology of site-specific cocaine abuse treatment agents: 2-(Aminomethyl)-3-phenylbicyclo [2.2.2]- and - [2.2.1] alkane dopamine uptake inhibitors
Deutsch, Howard M.,Collard, David M.,Zhang, Liang,Burnham, Kikue S.,Deshpande, Abhay K.,Holtzman, Stephan G.,Schweri, Margaret M.
, p. 882 - 895 (2007/10/03)
As part of a program to develop site-specific medications for cocaine abuse, a series of 2-(aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane derivatives was synthesized and tested for inhibitory potency in [3H]WIN 35,428 binding and [3H]dopamine uptake assays using rat striatal tissue. Selected compounds were tested for their ability to substitute for cocaine in rat drug discrimination tests. Synthesis was accomplished by a series of Diels-Alder reactions, using cis- and trans-cinnamic acid derivatives (nitrile, acid, acid chloride) with cyclohexadiene and cyclopentadiene. Standard manipulations produced the aminomethyl side chain. Many of the compounds bound with high affinity (median IC50 = 223 nM) to the cocaine binding site as marked by [3H]WIN 35,428. Potency in the binding assay was strongly enhanced by chlorine atoms in the 3- and/or 4-position on the aromatic ring and was little affected by corresponding methoxy groups. In the [2.2.2] series there was little difference in potency between cis and trans compounds or between N,N-dimethylamines and primary amines. In the [2.2.1] series the trans exo compounds tended to be least potent against binding, whereas the cis exo compounds were the most potent (4-Cl cis exo: IC50 = 7.7 nM, 27-fold more potent than 4-Cl trans-exo). Although the potencies of the bicyclic derivatives in the binding and uptake assays were highly correlated, some of the compounds were 5-7-fold less potent at inhibiting [3H]-dopamine uptake than [3H]WIN 35,428 binding (for comparison, cocaine has a lower discrimination ratio (DR) of 2.5). The DR values were higher for almost all primary amines and for the trans-[2.2.2] series as compared to the cis-[2.2.2]. Most of the compounds had Hill coefficients approaching unity, except for the [2.2.2] 3,4-dichloro derivatives, which all had n(H) values of about 2.0. Two of the compounds were shown to fully substitute for cocaine in drug discrimination tests in rats, and one had a very long duration of action.
Product Formation and Identification in the Reaction of 6-endo-Hydroxy-5-exo-iodo-3-exo-phenylnorborn-2-endo-ylcarboxylic Acid γ-Lactone with Silver Toluene-p-sulphonate
Sadikun, Amirin bin,Davies, David I.,Kenyon, Robert F.
, p. 1578 - 1582 (2007/10/02)
The reaction of 6-endo-hydroxy-5-exo-iodonorborn-2-endo-ylcarboxylic acid γ-lactone with silver toluene-p-sulphonate affords 7-syn-hydroxy-3-exo-tosyloxynorborn-6-exo-ylcarboxylic acid γ-lactone as the sole product.A comparable reaction with 6-endo-hydroxy-5-exo-iodo-3-exo-phenylnorborn-2-endo-ylcarboxylic acid γ-lactone affords a mixture of 6-endo-hydroxy-3-exo-phenyl-5-exo-tosyloxynorborn-2-endo-ylcarboxylic acid γ-lactone, 7-syn-hydroxy-5-endo-phenyl-3-exo-tosyloxynorborn-6-exo-ylcarboxylic acid γ-lactone, and 2-exo-hydroxy-4-phenylnorborn-5-en-7-anti-ylcarboxylic acid γ-lactone.Product formation is discussed in terms of possible carbocation intermediates.The latter product is unusual in that the position of the bridgehead C-1 proton in the 1H n.m.r. spectrum is similar to that of the aromatic protons.Product structures were determined by n.m.r. spectroscopic studies, and by chemical conversions.
