Electrophilic groups

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. 

Path c. The electrophilic group (in this case NOj) can undergo a 1,2 migration, followed by loss of the proton. The product in this case is the same as that obtained by direct attack of NOj at the ortho position of PhZ. It is not always easy to tell how much of the ortho product in any individual case arises from this pathway, though there is evidence that it can be a considerable proportion. Because of this possibility, many of the reported conclusions about the relative reactivity of the ortho, meta, and para positions are cast into doubt, since some of the product may have arisen not from direct attack at the ortho position, but from attack at the ipso position followed by rearrange-... 

In the presence of substances that react with Ag , the 340 nm absorption decays more rapidly and the rate constant of reaction can be calculated from this decay. It was found in this way that free silver atoms are indeed a strongly reducing species. They reduce Fe to Fe and Cu to Cu (note that these reactions would not occur with the silver atoms at the surface of a compact electrode ) organic compounds containing electrophilic groups such as CICH2COOH or CH3NO2 are reduced by Ag via electron transfer... 

Figure 9,1 Examples of carbons activated by neighboring electrophilic groups ...

PCI-32765 1 is the only Btk inhibitor which has been reported to have advanced to clinical trials [40]. Modeling of pyrazolopyrimidine 2 suggested that replacement of the cyclopentyl moiety could position an electrophilic group in proximity to Cys481, and subsequent optimization led to 1 [41]. Compound 1 inhibits Btk with an IC50 of 0.8 nM, and covalent binding to Btk was confirmed by mass spectrometry and washout experiments. In the Ramos B-cell line, 1 inhibits BCR-induced calcium... 

Figure 17.18 The Staudinger ligation reaction uses a modified phosphine derivative containing an electrophilic group that acts as a trap for the nucleophilic nitrogen in the intermediate aza-ylide. The resultant shift yields an amide bond derivative between the phosphine-containing molecule and the azide-containing molecule.

Figure 17.23 A traceless Staudinger ligation process involves the formation of an intermediate aza-ylide with subsequent attack of the nucleophilic nitrogen atom on the neighboring electrophilic group. The formation of an amide bond then occurs concomitant with the loss of the phosphine component, thus forming a zero-length crosslink between the two molecules.

G. Forat, J.-M. Mas, L. Saint-Jalmes (Rhone-Poulenc Chimie). Method for Grafting a Substituted Difluoromethyl Group to a Compound Containing an Electrophilic Group with Microwave Irradiation. PCT International Application WO 5, 609,1998 (FR Application 96/ 9,754, 1 Aug 1996) Chem. Abstr. 1998, 128, 166999u. 

Seebach et The common features are a negative charge, a strong electrophilic group, and one of the most important functional groups of organic chemistry in both cases. But nucleophilic acylation of course is more important than nucleophilic halo-alkylation. With the Schemes 20—24 will be shown how the conception outlined before can be further developed. 

The use of methanol or ethanol as solvent (or sometimes the molecule of water resulting from the spontaneous dehydration) often leads to the isolation of a Fischer-type alkoxy- or hydroxy-carbene [M]=C(OR)CH=CR R instead of the desired allenylidene. Addition of nucleophiles to allenylidenes dominates the reactivity of these electrophilic groups (see below). Nevertheless, in some cases, the use of silver (I) salts Ag[X] (X = PFg, TfO, BF4 ) results in a more practical and flexible synthetic method since the use of nucleophilic polar solvents can be avoided. 

This alternative method for the synthesis of thiolinkages involved the displacement of an electrophilic group at C-1 of donor molecules with a thiolate at the primary or secondary position of acceptors. 

These antitumor agents are compounds that form carbonium ions or other reactive electrophilic groups. Such compounds bind covalently to DNA, and either crosslink the two strands of the helix or otherwise interfere with replication or transcription. Since these processes are more prevalent in rapidly dividing malignant cells than in normal tissues, alkylating agents can control and in some cases even eliminate tumors. However, their selectivity is limited and they have many and serious side effects. 

Usually, PEG-protein conjugates are prepared by the reaction between methoxypolyethylene glycol (mPEG) carrying a reactive electrophile group... 

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