Scavengers of electrophiles

From experiments conducted with OPZ administered before, during, and after AFBl, it was concluded that OPZ acts as a blocking rather than a suppressive chemoprotective agent [29]. Such an anti-initiating agent can, in principle, act at several levels, including inhibition or induction of CYPs, induction of phase 2 enzymes, scavenging of electrophilic metabolites and ROS, and induction of DNA repair [30]. 

Protection against cell damage due to oxidative stress is provided, amongst others, by glutathione (GSH), a cellular tripeptide with a thiol function in a cysteine residue. GSH is deprotonated to GS, which is a scavenger for electrophilic compounds and is reduced to GS SG in defense of reactive oxygen species [28]. 

The allenylsilanes are excellent nucleophiles and they can react with a variety of electrophilic species in annulation processes that provide access to diverse products. Allenylsilane 112 (Eq. 13.36) reacts with tropylium fluoroborate 111 to provide azu-lene 113 [35]. The reaction is slow and it is necessary to use an acid scavenger so as to inhibit protiodesilylation by the fluoroboric acid that is generated during the course of the annulation. The excess tropylium salt abstracts a hydride from the reaction intermediate leading to the azulene. There are relatively few direct methods for the synthesis of azulenes. 

Scheme 2.11 Polyamine scavenger purification of electrophilic reagents.

The composition of the products from the alkylation of lithiated 3,6-dialkoxy-2,5-dihydropy-razines with bis-alkylating reagents depends on the equivalents of electrophile employed. For example, with three equivalents of bis-alkylating electrophiles, (25)-2,5-dihydro-2-isopropyi-3,6-dimethoxy-5-methylpyrazine (I) gives high yields of the 1 1 adducts 2 or 5 with > 97% de2. These products can be further converted to the bicyclic systems (3 and 6. respectively) which, upon hydrolysis, give optically pure cyclic amino acids (4 and 7). Methyloxirane is used as an acid scavenger in order to release the free amino acid zwitterion. 

This strategy has previously been referred to as t A nucleophilic polymer is a scavenger of solid-supported scavengers (SSS), polymer- electrophiles and vice versa,... 

A PET in intramolecular CPs between pyridinium ions and bromide, chloride or thiocyanate ions for polymerization initiation is described, too [137-139]. As expected, an equilibrium exists among free ions, ion pairs, and CT, which is shifted to the free ions in polar solvents and to the complex in a less polar solvent That complex serves as the photosensitive species for the polymerization (see Scheme 10). The photodecomposition of the CT yields radicals of the former anion and N-alkylpyridinyl radicals. Probably, the photopolymerization is initiated only by X- radicals, whereas latter radicals terminate the chain reaction. By addition of tetrachloromethane, the polymerization rate is increased owing to an electron transfer between the nucleophilic pyridinyl radical and CC14 (indirect PET). As a result, the terminating radicals are scavenged and electrophilic -CQ3 radicals are produced. 

The concept of selective sequestration of non-product species was first demonstrated using solid-supported scavengers with electrophilic and nucleophilic character in amine acylation, amine alkylation, and reductive amination protocols [46]. Since then, a wide range of scavenger reagents has become commercially available from various suppliers. The structures and functions of these scavenger resins are shown in Table 1. 

Table 8.1 Summary of electrophilic/nucleophile scavengers developed to date.

Supported/Tagged Reactive Functionalities for the Sequestration of Electrophiles (Electrophile/Nudeophilic Scavengers)... 

Amine scavengers have been one of the most developed and widely used to remove a range of electrophiles on several different platforms. Traditionally developed on a polystyrene bead, amine scavengers have been utilized in natural products or library synthesis to yield high purity via a facilitated protocol. In 2005, Liu reported the use of a polystyrene-bound amine scavenger for the removal of excess aldehydes to provide imidazole derivatives in high purity without the need for classical purification (Scheme 8.30) [42]. 

Nanoparticles of semiconductor compounds (MA) may be formed from scavenging of radiolytic species produced by irradiation. The cationic part M is for example provided by a soluble salt, while the anionic part A is generated by cleavage after electron attachment to a soluble electrophile substitute RA as a precursor. and A are selected for their very low solubility product ... 

In some cases the addition of electrophilic alkenes, such as 4-allyl-1,2-dimethoxybenzene, to the reaction mixture can improve the outcome of the reaction, particularly when run in the presence of thioglycosides, by scavenging a by-product of the reaction, phenylsulfenyl tritlate. Non-carbohydrate thioacetal sulfoxides also undergo similar acetalation reactions when treated with Tf20 (eq71).i ... 

The mechanism of cytoprotection for amifostine is similar to that of other thiols. Once dephosphoryl-ated to actifostine [equation 270], the active thiol can scavenge oxygen free radicals (Ohnishi et al. 1992) and bind to a variety of electrophilic agents. 

Scavenging of free phosphines by electrophiles such as protons, other metals, conjugated enones, etc. presents a potential route to phosphine loss in catalytic systems. As yet, the participation of phosphonium intermediates has not been reported for rhodium hydroformylation catalysts, but they could be easily conceived, especially when dienes or enones are also present. 

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