Functional group electrophilic

Affinity Labels. Active site-directed, irreversible inhibitors or affinity labels are usually substrate analogues that contain a reactive electrophilic functional group. In the first step, they bind to the active site of the target enzyme in a reversible fashion. Subsequentiy, an active site nucleophile in close proximity reacts with the electrophilic group on the substrate to form a covalent bond between the enzyme and the inhibitor, typically via S 2 alkylation or acylation. Affinity labels do not require activation by the catalysis of the enzyme, as in the case of a mechanism-based inhibitor. 

Like the piperidones, a wide variety of TV-heterocyclic aromatic compounds show an ability to activate electrophilic functional groups. It is known that acetophenone is completely protonated in CF3SO3H, however in the presence of benzene there is no hydroxyalkylation (condensation) reaction.12 On the other... 

Trifluoromethyl)trimethylsilane has been prepared by a modification5 of the procedure originally published by Ruppert.4 The optimized yield is 75%. Other less convenient methods are also available for its preparation. (Trifluoromethyl)trimethylsilane acts as an in situ trifluoromethide equivalent under nucleophilic initiation and reacts with a variety of electrophilic functional groups. Carbonyl compounds such as aldehydes, ketones and lactones react rather readily5 7 with (trifluoromethyl)trimethylsilane under fluoride initiation. The reagent also reacts with oxalic esters,8 sulfonyl fluorides,9 a-keto esters,10 fluorinated ketones,11 and... 

An interesting arylation of the silyl enolate of Ley s dioxanone 133 in the presence of a catalytic amount of Pd2(dba)3 (5 mol%) and P(/-Bu)3 (10 mol%) with 0.5 equiv of Znp2 or Zn(0-/-Bu)2 provides a single diastereoisomer of the coupled products 134 (dba = dibenz[ , ]anthracene). A variety of electronically and sterically distinct aryl halides, including those containing electrophilic functional groups, have been introduced (Equation 20) <2004JA5182>. 

Electrophilic functional groups in ortho-position to the carbon-magnesium bond allow two sequential alkylations. Starting from ort/io-iodobenzyl chloride 104, the benzannulated heterocycles 105 and 106 are obtained after the reaction with appropriate electrophiles (Scheme 8) . ... 

Addition to carbon bearing the halogen 1 heteroatom such as N, S, or O, or double bond, or aryl group at a- or >position Increase alkylating activity by facilitating the departure of halogen and/or provide additional electrophilic functional group... 

Positioning all electrophilic functional groups in the middle of the molecule with none at any terminal positions will reduce molecular flexibility and accessibility of the electrophilic functional group(s) to interact with cellular nucleophiles such as DNA. 

There also are numerous enzymes that use bound metal ions to form complexes with substrates. In these enzymes, the metal ion usually serves as an electrophilic functional group rather than as a nucleophile. Carbonic anhy-drase, for example, contains a Zn+2 ion that binds one of the substrates, hydroxide ion, as a ligand. The bound OH reacts with the other substrate, C02. In alcohol dehydrogenase, and in the proteolytic enzymes thermolysin and car-boxypeptidase A, a Zn+2 ion forms a complex with a carbonyl oxygen atom of the substrate. The withdrawal of electrons by the Zn+2 increases the partial positive charge on the carbonyl carbon and thus promotes reaction with a nucleophile. 

Electrophilic carbon species are most often stable compounds with an electrophilic functional group present. Since they are stable molecules, they need not be generated as transients in the reaction mixture. The functional types which are good electrophiles have been defined earlier in this chapter and, the preparations of these functional groups were oudined in the previous chapter. 

E. Other Electrophilic Functional Groups on Aliphatic Compounds. . 126... 

No systematic study has been made to date on electrophilic functional groups of aliphatic compounds other than the carbonylic group and the halogens. 

The hydrocarbon framework of organic molecules is unreactive. Functional groups such as NH2 and OH are nucleophilic because they have nonbonding lone pairs. Carbonyl compounds and alkyl halides are electrophilic functional groups because they have low-energy LUMOs (it for 0=0 and G for C-X, respectively). 

All of these disconnections relied on the reaction of a carbon electrophile with a nucleophilic functional group. The alternative, reaction of a carbon nucleophile (such as a Grignard reagent) with an electrophilic functional group, allows us to do C-C disconnections on alcohols, For example, this compound, which has a fragrance reminiscent of lilac, is a useful perfume for use in soap because (unlike many other perfumes that are aldehydes or ketones) it is stable to alkali. 

So far we have discussed polymerization that has been essentially of one kind—bifunctional molecules have combined in normal ionic reactions familiar from the rest of organic chemistry where a nucleophilic functional group attacks an electrophilic functional group. The new bonds have generally been G-O or C-N. We need now to look at the polymerization of alkenes. In these reactions, n r knnric will bp for ed and many of the reactions may be new to you,... 

Reaction of R- M with other electrophilic functional groups (Section 20.14)... 

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