Michael receptors

Verbitski SM, Mullally JE, Fitzpatrick FA, Ireland CM (2004) Punaglandins, Chlorinated Prostaglandins, Function as Potent Michael Receptors to Inhibit Ubiquitin Isopeptidase Activity. J Med Chem 47 2062... 

Baizer and Chruma reported electrolytic reductive coupling, in a broad study in which reduction of organic halides was conducted in the presence of electrophiles as seen in equation 1034. Controlled potential electroreduction of reactive halides at a mercury cathode in the presence of olefinic substrates with electron-withdrawing groups (Michael receptors) gave moderate yields (50-75% in many cases) of carbanion addition products35. Current yields in excess of 100% in the case where chloroform was used as a cosolvent with carbon tetrachloride indicated the intervention of electrocatalytic reactions (equations 10 and 11). 

While zeolites are mostly used in acid catalysts, there are various procedures to introduce basic sites with variable strength into these materials. Depending on the nature of the active site, one is able to selectively catalyze reactions with different basicity requirements, and this is probably the main virtue of base catalysis with zeolites. For instance, in a classical Knoevenagel condensation, the reaction selectivity can be decreased by a consecutive Michael reaction, since the Knoevenagel product can serve itself as a Michael receptor -. 

When the Michael receptors are chiral, diastereoselective cyclopropanation reactions are possible. Treatment of an enan-tiomerically pure (+)-dicyclopentadienone with EDS A gave the eA o-cyclopropane product in 88% yield in >99% ee. Thermolysis of this adduct gave, via a retro-Diels-Alder reaction, an optically active (>99% ee) cyclopentenone in 82% yield (eq 8), ... 

Michael Addition. Methallyl phenyl sulfone has been a good partner with a variety of different Michael receptors. Addition to enones using / BuLi as base at —78 °C gave the desired products in good yields. Methyl vinyl ketone afforded the Michael adduct in 61% yield (eq 7). Reaction of methallyl sulfone with 2-hexenone and 2-methyl-2-pentenone in the presence of HMPA provided the conjugate addition products in 91% yield and 79% yield, respectively (eqs 8 and 9).lO.Ha... 

Michael addition to substituted enoates has proven diastereo-selective. Ethyl ( )-crotonate or ethyl ( )-cinnamate afforded conjugate addition adducts in 92% yield and 87% yield with anfi/sj73-diastereomeric ratios of 85/15 and 100/0, respectively (eq 10) whereas in the presence of HMPA the diastereoselectiv-ity was reversed. With the y-oxygenatedenoate, anfr-diastereo-selectivity resulted HMPA improved the selectivity from 8/1 to 12/1 (eq 11). Similar results were obtained with a conjugated lactone (eq 12). Ethyl ynoate also acted as a reactive Michael receptor for the methallyl sulfone (eq 13). Other conjugated substrates such as nitroolefins and acrylonitrile proved to be appropriate Michael receptors as well. 

Bromo methallyl sulfone, prepared from methallyl phenyl sulfone, has proven to be a good substrate for stereoselective synthesis of trisubstituted methylenecyclopentanes with a variety of different Michael receptors. For example, the trans trans-trisubstituted methylenecyclopentane was efficiently prepared in 93% yield by a cascade Michael addition/cyclization beginning with ethyl ( )-crotonate (eq 22). The phosphonate sulfone reagent, readily available from methallyl phenyl sulfone, was used for the selective synthesis of 1,3-dienes. The synthesis included... 

Table 3.1. Conjugate addition of amines to Michael receptors.

This section is further subdivided by the type of Michael receptor that is used. In this part, conjugated esters will be reacted with various amine surrogates. 

Solid phase 7 represents a regenerative Michael receptor (REM), since on addition of phenylpiperazines I, a library of solid-phase derivatives II is formed. On benzylation by benzylbromides III, quartemary amonium salts IV are formed. 

Phenylseleno)-2-propenal serves as an efficient Michael receptor of Grig-nard reagents giving allylic alcohols (43). Treatment of these with 2 equivalents of m-chloroperbenzoic acid followed by base gave a smooth conversion to oxetans (44) and (45) (Scheme S). Close examination showed that both E- and Z-propenal usually gave the c/5-oxetan predominantly. 

Ethyl 3-nitroacrylate is an extremely reactive receptor in the Michael reaction. It has found use in the synthesis of the a-methylene-butyrolactone moiety3 characteristic of many sesquiterpenes, as shown... 

Saito Y, Sharer LR, Epstein LG, Michaels J, Mintz M, Louder M, Golding K, Cvetkovich TA, Blumberg BM (1994) Overexpression of nef as a marker for restricted HIV-1 infection of astrocytes in postmortem pediatric central nervous tissues. Neurology 44 474-481 Sargeant TJ, Day DJ, Mrkusich EM, Eoo DE, Miller JH (2007) Mu opioid receptors are expressed on radial glia but not migrating neuroblasts in the late embryonic mouse brain. Brain Res 1175 28-38... 

Adenosine and Adenosine Receptors, edited by Michael Williams, 1990... 

More recently attempts to generate highly selective quiescent affinity labels have been made for a number of protease and kinase targets. As examples, inhibitors of the Rhinovirus 3C protease (Mathews et al 1999) and of the epidermal growth factor receptors (Boschelli, 2002), both incorporating Michael acceptors to covalently inactivate cysteine residues in their target enzymes (Lowry and Richardson, 1981 Figure 8.6), have entered human clinical trials for the treatment of rhinovirus infection and cancer, respectively. 

Costentin, J., Duterte-Boucher, D., Panissaud, C., and Michael-Titus, A. Dopamine D, and D2 receptors mediate opposite effects of apomorphine on the body temperature of reserpinized mice. Neuropharmacology. 29 31, 1990. 

Adie EJ, Kalinka S, Smith L, Francis MJ, Marenghi A, Cooper ME, Briggs M, Michael P, Milligan G, Game S (2002) A pH-sensitive fluor, CypHer 5, used to monitor agonist-induced G protein-coupled receptor internalization in live cells. BioTechniques 33 1152-1157... 

Michael SI, Huang CH, Romer MU, Wagner E, Hu PC, Curiel DT (1993) Binding-incompetent adenovirus facilitates molecular conjugate-mediated gene transfer by the receptor-mediated endocytosis pathway. J Biol Chem 268 6866-6869... 

TOXICANT-RECEPTOR INTERACTIONS MODULATION OF SIGNAL TRANSDUCTIONS AND GENE EXPRESSION Michael S. Denison and William G. Helferich, editors, 256pp., 1998... 

Cornea, A. and Michael Conn, P. (2002) Measurement of changes in fluorescence resonance energy transfer between gonadotropin-releasing hormone receptors in response to agonists. Methods 27, 333. 

A high plasma concentration of LDL (usually measured as LDL-cholesterol) is a risk factor for the development of atheroma whereas a high concentration of HDL is an anti-risk factor for cardiovascular disease (CVD). Fundamental discoveries relating to cholesterol metabolism and the importance of the LDL receptor made by Nobel laureates Joseph Goldstein and Michael Brown led to an understanding of the role of LDL in atherosclerosis. The impact of HDL in reducing CVD risk is often explained by the removal of excess cholesterol from tissues and its return to the liver, a process known as reverse cholesterol transport. However, evidence from research by Gillian Cockerill and others shows that HDL has a fundamental anti-inflammatory role to play in cardioprotection. 

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