Nucleophilic acceptor

The sulfoxide method was introduced by Kahne and coworkers,1 and was heralded as a new method for rapid glycosylation of unreactive substrates in high yield under mild conditions. The reaction involves the sulfoxide donor [sulfoxide (I)], an activating agent (usually triflic anhydride), a hindered, nonnucleophilic base (2,6-di-tert-butyl-4-mcthylpyridine, DTBMP) and a nucleophilic acceptor (most often an alcohol) (Scheme 3.1). The glycosylation of sterically hindered steroidal alcohols, phenols and the /V-glycosylation of an acetamide was reported (Table 3.1). 

Transition metal complexes which react with diazoalkanes to yield carbene complexes can be catalysts for diazodecomposition (see Section 4.1). In addition to the requirements mentioned above (free coordination site, electrophi-licity), transition metal complexes can catalyze the decomposition of diazoalkanes if the corresponding carbene complexes are capable of transferring the carbene fragment to a substrate with simultaneous regeneration of the original complex. Metal carbonyls of chromium, iron, cobalt, nickel, molybdenum, and tungsten all catalyze the decomposition of diazomethane [493]. Other related catalysts are (CO)5W=C(OMe)Ph [509], [Cp(CO)2Fe(THF)][BF4] [510,511], and (CO)5Cr(COD) [52,512]. These compounds are sufficiently electrophilic to catalyze the decomposition of weakly nucleophilic, acceptor-substituted diazoalkanes. 

The glycosyl transferases (E.C. 2.4 group) usually show high specificity towards the structure of the glycosyl acceptor. Furthermore, the enzyme specificity seems to determine which of the available nucleophilic acceptor-groups participates in the reaction, and also determines the stereospecificity of the glycosylation. 

The competition between transferase and hydrolysis reactions can be described in terms of nucleophile (acceptor) selectivities of the enzymes, and selectivity constants can be defined. These constants are meant to quantify the intrinsic selectivity of the enzymes. Selectivity constants in combination with the concentrations (or thermodynamic activities) of the competing nucleophiles give the transferase/hydrolysis ratio. The selectivity constants are defined as follows [38, 39] ... 

The electrophilicity or nucleophilicity ("acceptor or "donor character, respectively) of the carbamoyl radical is now being studied in our laboratory. 

The activation mechanism of phosphosulfate linkages (P—O —S)has been studied to understand the chemistry of biological sulfate-transfer reactions of phosphosul-fates of adenosine (APS and PAPS). Several phosphosul-fates were prepared and subjected to several nucleophilic reactions including hydrolysis. In general, phosphosulfates are stable in neutral aqueous mediay but become labile under acidic conditions, resulting in selective S—O fission. This S—O fission appears to occur by unimolecular elimination of sulfur trioxide, which can react with a nucleophilic acceptor, leading to a sulfate-transfer reaction. This process can be accelerated by Mg2+ ion when the solvent is of low water content. Under neutral conditions, divalent metal ions also were found to catalyze nucleophilic reactions, but these occurred on phosphorus to result in exclusive P-O fission. 

Phosphosulfates may react with a nucleophile (Nu) in either of the two modes of P-O or S-O bond fission (Figure 2). If water is the nucleophile, both modes of fission result in the same hydrolysis products. Mechanistically, however, the enzymes that catalyze P—O fission may be regarded as phosphatases, while those that catalyze S—O fission are sulfohydrolases. In fact, many hydrolytic enzymes are assumed to be sulfohydrolases without mechanistic proof. The possibility that they might be phosphatases was suggested by Roy by taking account their metal ion dependency (4). Meanwhile, PAPS acts as the sulfate donor to numerous nucleophilic acceptors such as steroids and phenols. In such sulfate transfer reactions, S—O fission must occur. PAPS and APS also are known to act as the key intermediates in the reduction of sulfate to sulfite. Here again, the S—O fission may be the most probable mode. 

In model systems the transfer of the 2-acyl group from 2-acylThDP to a variety of nucleophilic acceptors, including thiols, was found to be exceedingly sluggish72-74. 

This sequence of reactions therefore requires several enzymes that have not yet been separated from each other. As the methylation step is NADPH-dependent,7 it may be postulated that reduction at C-2 occurs before methylation at C-3. In Scheme 1, the 3,4-enediol of the hexos-4-ulose 5 is shown as the nucleophilic acceptor for the methyl group from AdoMet, but the existence of such an enediol has not been proved. 

On the other hand, conjugated nitroalkenes are very useful electron-poor alkenes, prone to act as nucleophilic acceptor, mainly in the Michael reaction (Berestovitaskaya et al., 1994) or in the Diels-Alder cycloaddition (Denmark and Thorarensen, 1996). Moreover, the nitro group can be easily turned into a respectable array of functional groups such as its reduction to a primary amine, replacement with hydrogen (Ballini et al., 1983 Ono, 2001), conversion into a carbonyl (Nef reaction) (Ballini and Petrini, 2004), and transformation into other important functionalities such as nitrile, nitrile oxide, oximes, hydroxylamines, and thiols (Colvin et al., 1979). 

By definition enzymes that are able to oxidize chloride, bromide, and iodide are called chloroperoxidases and those able to oxidize bromide and iodide, bromoperoxidases. If a nucleophilic acceptor (RH) is present, a reaction will occur with HOX and halogenated compounds see Halocarbons Halocarbon Complexes) are produced (equation 2). 

On the basis of kinetic stndies the presence of a peroxo-intermediate was postdated and spectroscopic evidence for such an intermediate has been obtained. Brs", Br2, or HOBr appear to be the primary reaction prodncts of the enzyme-mediated peroxidation of bromide. The vanadium enzyme also nses phenylperacetic acid, m-chloroperoxybenzoic acid, and jo-nitroperoxybenzoic acid as oxidants, but alkyl peroxides such as ethylhydroperoxide, tert-butyl hydroperoxide, and cuminyl hydroperoxide are not substrates for the enzyme in the oxidation of bromide. The enzyme from the brown seaweed Ascophyllum nodosum does not display any specificity with regard to bromination of various organic nucleophilic acceptors which suggests a mechanism in which the oxidized bromine species are released into solution by the enzyme. Figure 1 gives a simple model for the reaction mechanism of the enzyme. 

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