Stabilisation of methylene radicals by cob(II)alamin in coenzyme B12 dependent mutases

Coenzyme B12 initiates radical chemistry in two types of enzymatic reactions, the irreversible eliminases (e.g., diol dehydratases) and the reversible mutases (e.g., methylmalonyl-CoA mutase). Whereas eliminases that use radical generators other than coenzyme B12 are known, no alternative coenzyme B12 independent mutases have been detected for substrates in which a methyl group is reversibly converted to a methylene radical. We predict that such mutases do not exist. However, coenzyme B12 independent pathways have been detected that circumvent the need for glutamate, beta-lysine or methylmalonyl-CoA mutases by proceeding via different intermediates. In humans the methylcitrate cycle, which is ostensibly an alternative to the coenzyme B12 dependent methylmalonyl-CoA pathway for propionate oxidation, is not used because it would interfere with the Krebs cycle and thereby compromise the high-energy requirement of the nervous system. In the diol dehydratases the 5'-deoxyadenosyl radical generated by homolysis of the carbon-cobalt bond of coenzyme B12 moves about 10 A away from the cobalt atom in cob(II)alamin. The substrate and product radicals are generated at a similar distance from cob(II)alamin, which acts solely as spectator of the catalysis. In glutamate and methylmalonyl-CoA mutases the 5'-deoxyadenosyl radical remains within 3-4 A of the cobalt atom, with the substrate and product radicals approximately 3 A further away. It is suggested that cob(II)alamin acts as a conductor by stabilising both the 5'-deoxyadenosyl radical and the product-related methylene radicals.     

The Co(I) induced methylmalonyl-succinyl rearrangement in a model for the coenzyme B12 dependent methylmalonyl-CoA mutase

The rearrangement of 2-bromomethyl-2-methylmonothiomalonates to succinyl derivatives was found to take place in quantitative yields in the presence of one molar equivalent of Co(I) generated by the reduction of heptamethyl Co(II)yrinate perchlorate with NaBH4 or electrochemically. The chiral thiomalonate gave racemic succinate.     

Electron-transfer oxidation of coenzyme B12 model compounds and facile cleavage of the cobalt(IV)-carbon bond via charge-transfer complexes with bases. A negative temperature dependence of the rates

The electron-transfer oxidation and subsequent cobalt-carbon bond cleavage of vitamin B12 model complexes were investigated using cobaloximes, (DH)2Co(III)(R)(L), where DH- = the anion of dimethylglyoxime, R = Me, Et, Ph, PhCH2, and PhCH(CH3), and L = a substituted pyridine, as coenzyme B12 model complexes and [Fe(bpy)3](PF6)3 or [Ru(bpy)3](PF6)3 (bpy = 2,2'-bipyridine) as a one-electron oxidant. The rapid one-electron oxidation of (DH)2Co(III)(Me)(py) (py = pyridine) with the oxidant gives the corresponding Co(IV) complexes, [(DH)2Co(IV)(Me)(py)]+, which were well identified by the ESR spectra. The reorganization energy (lambda) for the electron-transfer oxidation of (DH)2Co(Me)(py) was determined from the ESR line broadening of [(DH)2Co(Me)(py)]+ caused by the electron exchange with (DH)2Co(Me)(py). The lambda value is applied to evaluate the rate constants of photoinduced electron transfer from (DH)2Co(Me)(py) to photosensitizers in light of the Marcus theory of electron transfer. The Co(IV)-C bond cleavage of [(DH)2Co(Me)(py)]+ is accelerated significantly by the reaction with a base. The overall activation energy for the second-order rate constants of Co(IV)-C bond cleavage of [(DH)2Co(IV)(Me)(py)]+ in the presence of a base is decreased by charge-transfer complex formation with a base, which leads to a negative activation energy for the Co(IV)-C cleavage when either 2-methoxypyridine or 2,6-dimethoxypyridine is used as the base.     

A homogeneous, recyclable polymer support for Rh(I)-catalyzed C-C bond formation

A robust and practical polymer-supported, homogeneous, recyclable biphephos rhodium(I) catalyst has been developed for C-C bond formation reactions. Control of polymer molecular weight allowed tuning of the polymer solubility such that the polymer-supported catalyst is soluble in nonpolar solvents and insoluble in polar solvents. Using the supported rhodium catalysts, addition of aryl and vinylboronic acids to the electrophiles such as enones, aldehydes, N-sulfonyl aldimines, and alkynes occurs smoothly to provide products in high yields. Additions of terminal alkynes to enones and industrially relevant hydroformylation reactions have also been successfully carried out. Studies show that the leaching of Rh from the polymer support is low and catalyst recycle can be achieved by simple precipitation and filtration.     

A direct access to 3-(2-Oxoalkyl)indoles via aluminum chloride induced C-C bond formation

3-Methylindole is acylated regioselectively at the methyl group when treated with a variety of acyl chlorides in 1,2-dichloroethane in the presence of AlCl(3), affording a mild and direct method for the synthesis of 3-(2-oxoalkyl)indoles. The product formation in this one-pot reaction largely depends on the conditions of the reaction employed. The methodology does not require protection-deprotection steps and is amenable for the scale-up synthesis of these indole derivatives.     

A reaction for sp(3)-sp(3) C-C bond formation via cooperation of Lewis acid-promoted/Rh-catalyzed C-H bond activation

A new method for intermolecular sp3-sp3 C-C bond formation between primary aliphatic alcohol and olefin by use of a RhCl(PPh3)3 (cat.)/BF3.OEt2 (2.5 equiv)/BuBr (0.5 equiv)/toluene system was first disclosed, which possessed quite significant utilities for organic synthesis, especially for that of secondary alcohols. The most significant aspect is the discovery that rhodium-catalyzed C-H bond activation of alcohols is feasible under Lewis acid-promoted conditions.     

Stereochemistry of internucleotide bond formation by the H-phosphonate method. 7. Stereoselective formation of ribonucleoside (RP)- and (SP)-3′-H-phosphonothioate monoesters

Ribonucleoside 3′-H-phosphonothioate monoesters exist in the form of (R_P)- and (S_P)-diastereomers. In order to obtain them in good yields and in high stereochemical purity, stereoselective strategies for their preparation were investigated. For the synthesis of the (R_P)-isomer, a stereoselective sulfhydrolysis of an activated nucleoside H-phosphonate was developed, while the monoesters with an (S_P)-configuration were prepared by asymmetric transformation of diastereomeric mixtures of nucleoside 3′-H-phosphonothioates using either a condensation with 9-fluorenemethanol, followed by β-elimination, or via pivaloylation-hydrolysis reaction sequence. A tentative assignment of the absolute configurations of the obtained diastereomers of 3′-H-phosphonothioate esters was carried out via a stereochemical correlation analysis.     

Studies in the complex formation of metal ions with sugars. I. The complex formation of cobalt(II), cobalt(3), copper(II) and nickel(II) with mannitol

The use of elastic polyurethane foam as a support for chloranil was proved successful. Reductions of cerium(IV), vanadium(V) and iron(II) on foam-filled columns were carried out quantitatively and rapidly. The effect of flow-rate and temperature on the reduction of each metal ion was examined in detail. Cerium(IV) was reduced quantitatively on passing through the foam-redox column at flow-rates of 2–11 ml min^-1 at room temperature. The reduction of vanadium(V) and iron(III) was slower; complete reduction occurred only at flow-rates up to 4 and 2 ml min^-1 for V(V) and Fe(III), respectively. At 35°, however, it was possible to use flow-rates of 7 and 6 ml min^-1 for the quantitative reduction of V(V) and Fe(III), respectively.     

BF3.Et2O-catalyzed direct carbon-carbon bond formation of alpha-EWG Ketene-(S,S)-acetals and alcohols and synthesis of unsymmetrical biaryls

A highly efficient BF3.OEt2-catalyzed formal dehydration C-C coupling reaction between readily available alpha-EWG ketene-(S,S)-acetals and various alcohols via direct substitution of the hydroxy group in alcohols has been developed. On the basis of this C-C coupling reaction, a series of alkylated alpha-EWG ketene-(S,S)-acetals and functionalized 1,4-pentanedienes were prepared in high to excellent yields and the unsymmetrical biaryls were synthesized in good yields from the generated 1,4-pentanedienes and nitroalkanes through a one-pot annulation-aromatization process.     

A MO-theoretical study of the hydrogen bond in (HCOOH)2, (HCONH2)2 and (B(OH)3)2

The energy decomposition scheme is used with the ab initio MO of the STO-3G minimal basis to elucidate the nature of hydrogen-bondings in (HCOOH)₂, (HCONH₂)₂ and (B(OH)₃)₂. The comparison of the interaction energy and its five components, together with that of the difference density map, reveals the similarity or the difference of these three systems. Each component of the global difference density represents the characteristic role of the corresponding interaction. While the effect of the exchange and charge-transfer interaction is limited to the hydrogen-bonded region, that of the polarization and the coupling terms is spread over the intramolecular bonds of each monomer. The analysis of some orbital interactions is made with respect to (HCOOH)₂ and the importance of the particular charge-transfer interaction is demonstrated.     

ChemInform Abstract: Polyoxometalate Diphosphate Complexes. Folded Macrocyclic Dodecatungstates, ((O3PXPO3)4W12O36)16- (X: O,CH2).

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.     

Studies on the mechanism of the reaction between coenzyme B12 and cyanide: direct 1H NMR spectroscopic evidence for a (beta-5'-deoxyadenosyl)(alpha-cyano)cobalamin intermediate

The reaction between coenzyme B12 (5'-deoxyadenosylcobalamin, AdoCbl) and tetrabutylammonium cyanide to give dicyanocobalamin, adenine, and 1-cyano-D-erythro-2,3-dihydroxy-4-pentenol has been examined in 92% N,N-dimethylformamide (DMF)/8% D2O. Under these conditions rate-determining Co-C heterolytic cleavage is preceded by rapid addition of cyanide to AdoCbl to form an intermediate, (beta-5'-deoxyadenosyl)(alpha-cyano)cobalamin ((beta-Ado)(alpha-CN)Cbl-), identified by 1H NMR spectroscopy. Rate constants have been determined by both 1H NMR and visible spectroscopies, with the latter showing saturation kinetics. The observed rate constant is pH-independent in the pH region studied, and replacing D2O by H2O increases it by ca. 10%. Increasing the percentage of D2O in the DMF/D2O solvent mixture also increases the reaction rate, and for D2O > or = 50% there is a change in the rate-determining step, with formation of the (beta-Ado)(alpha-CN)Cbl- intermediate becoming rate-determining. A mechanism in 92% DMF/8% D2O is proposed which involves rapid reversible formation of (beta-Ado)(alpha-CN)Cbl- from base-off AdoCbl plus cyanide, followed by rate-determining solvent-assisted cleavage of the Co-C bond of the intermediate and subsequent rapid addition of a second cyanide to give the products.     

An enzymatic assay method for D(-)-3-hydroxybutyrate and acetoacetate involving acetoacetyl coenzyme A synthetase from Zoogloea ramigera

An enzyme assay method for D(-)-3-hydroxybutyrate and acetoacetate involving acetoacetyl coenzyme A (CoA) synthetase was developed. To determine the concentration of D-3-hydroxybutyrate, it was oxidized with D-3-hydroxybutyrate dehydrogenase in the presence of nicotinamide adenine dinucleotide (NAD+) to acetoacetate, which was then converted to acetyl CoA via acetoacetyl CoA through the combined actions of acetoacetyl CoA synthetase and 3-ketothiolase in the presence of adenosine triphosphate (ATP) and CoA. To determine the concentration of acetoacetate, acetoacetyl CoA generated from acetoacetate with acetoacetyl CoA synthetase was reduced to 3-hydroxybutyryl CoA with 3-hydroxyacyl CoA dehydrogenase in the presence of NADH. The amount of D-3-hydroxybutyrate or acetoacetate was estimated from the increase or decrease in the absorbance at 340 nm, respectively. The present assay method seemed to be accurate and quick. Furthermore, as to the assaying of D-3-hydroxybutyrate, the omission of hydrazine, which is included for the standard method, may be preferable for routine assaying.