Sulfuryl transfer reactions

Nucleoside Pyrophosphates. - 2.2.1 Nucleoside Diphosphate Analogues. The enzymatic regeneration of 3 -phosphoadenosine-5 -phosphosulfate (76) catalysed by the rat liver sulfotransferase IV enzyme has been reported to provide useful quantities of the cofactor for enzyme kinetic experiments. The first thio-nucleotide analogues of adenosine 5 -phosphosulfate (77a) and of 3 -phosphoadenosine 5 -phosphosulfate (77b) have been synthesised in enantio-merically pure forms. Using these novel analogues, the sulfuryl transfer reaction to adenosine 5 -triphosphate was shown to proceed with inversion of configuration at the a-phosphorus. ... 

Phosphoryl and sulfuryl transfer reactions are nucleophilic suhstitution reactions, and three limiting mechanisms can be envisioned. One is a dissociative S l-type mechanism, designated in the lUPAC nomenclature, in... 

Hengge AC. Isotope effects in the study ofphosphoryl and sulfuryl transfer reactions. 

Typical alkylation reactions are those of propane, isobutane, and n-butane by the ferf-butyl or sw-butyl ion. These systems are somewhat interconvertible by competing hydride transfer and rearrangement of the carbenium ions. The reactions were carried out using alkyl carbenium ion hexafluoroantimonate salts prepared from the corresponding halides and antimony pentafluoride in sulfuryl chloride fluoride solution and treating them in the same solvent with alkanes. The reagents were mixed at —78°C warmed up to — 20°C and quenched with ice water before analysis. The intermolecular hydride transfer between tertiary and secondary carbenium ions and alkanes is generally much faster than the alkylation reaction. Consequently, the alkylation products are also those derived from the new alkanes and carbenium ions formed in the hydride transfer reaction. 

Hengge AC. Isotope effects in the study of phosphoryl and sulfuryl 40. transfer reactions. Acc. Chem. Res. 2002 35 105-112. 

Scheme 2 Two potential reaction mechanisms for phosphatases or sulfatases are shown here using a phosphate ester. In (a), the phosphoryl group is transferred directly to a water molecule, which is typically bound to one or two metal ions if the substrate is made chiral at phosphorus, the stereochemical outcome is inversion. In (b), the phosphoryl group is first transferred to an enzymatic nucleophile E-POs " is a covalent phosphoenzyme intermediate. In a subsequent step, this intermediate is hydrolyzed. Since each step occurs with inversion of configuration at phosphorus, the net outcome is retention. The same principles apply to sulfuryl transfer. P, = inorganic phosphate.

Sulfuryl transfer, also referred to as sulfation or sulfonation is the transfer reaction of the sulfate group from the ubiquitous donor 3 -phosphoadenosine 5 -phosphosulfate (PAPS) to an oxygen atom of the acceptor substrate leading to a sulfuric acid ester (R — O — SO3, RR — N — O — SO3) (Fig. 31.41). 

Besides radical additions to unsaturated C—C bonds (Section III.B.l) and sulfene reactions (see above), sulfonyl halides are able to furnish sulfones by nucleophilic substitution of halide by appropriate C-nucleophiles. Undesired radical reactions are suppressed by avoiding heat, irradiation, radical initiators, transition-element ion catalysis, and unsuitable halogens. However, a second type of undesired reaction can occur by transfer of halogen instead of sulfonyl groups283-286 (which becomes the main reaction, e.g. with sulfuryl chloride). Normally, both types of undesired side-reaction can be avoided by utilizing sulfonyl fluorides. 

The sulfotransferases catalyze formation of sulfate esters of compounds having hydroxy or amino groups. The donor in this transfer of a sulfuryl group is 3 -phosphoadenylsulfate, also named previously as 3 -phosphoadenosine-5 -phos-phosulfate (PAPS). An example of this reaction is seen in Eq. (11) for phenol as the sulfuryl (S03) acceptor, with the products of the reaction being phenyl sulfate and adenosine 3, 5 -bisphosphate (PAP). 

Lewis superacid-catalyzed direct alkylation of alkanes is also possible with alkyl cations prepared from alkyl halides and SbFs in sulfuryl chloride fluoride solution. " Typical alkylation reactions are those of propane and butanes by 2-butyl and ZerZ-butyl cations. The ClfU-Sbfs and C2H5F-SbF5 complexes acting as incipient methyl and ethyl cations besides alkylation preferentially cause hydride transfer. Since intermolecular hydride transfer between different carbocations and alkanes are faster than alkylation, a complex mixture of alkylated products is usually formed. A significant amount of 2,3-dimethylbutane was, however, detected when propane was propylated with the 2-propyl cation at low temperature [Eq. (6.36)]. No 2,2-dimethylbutane, the main product of conventional acid-catalyzed alkylation, was detected, which is a clear indication of predominantly nonisomerizing reaction conditions. 

Stereochemistry is another powerful tool for determining the net reaction pathway of phosphatases and sulfatases. These enzymes catalyze the net transfer of a phosphoryl or sulfuryl group to water from a monoester, producing inorganic phosphate or sulfate. Inversion results when the reaction occurs in a single step (Scheme 2, pathway a). Phosphatases that transfer the phosphoryl group directly to water with inversion typically possess a binuclear metal center and the nucleophile is a metal-coordinated hydroxide. Examples of phosphatases that follow this mechanism are the purple acid phosphatases (PAPs) and the serine/threonine phosphatases (described in Sections 8.09.4.3 and 8.09.4.4.1). Net retention of stereochemistry occurs when a phosphorylated or sulfiirylated enzyme intermediate is on the catalytic pathway, which is hydrolyzed by the nucleophilic addition of water in a subsequent step (Scheme 2, pathway b). 

The reactive species under acidic conditions is the neutral ester. This reaction is believed to proceed by transfer of the proton from the sulfuryl group to the leaving group, as in reactions of phosphate monoester monoanions. A reduced value for d a solvent deuterium isotope effect of 2.43 " are consistent with proton transfer to the leaving group in the transition state. The intermediacy of free SO3 in the acid hydrolysis is sometimes assumed, but has not been proven. 

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