Arylphosphonic acids. II. General acid and general base catalysis of acetone enolization

Shelly, Kevin P.; Nagarajan, K.; Stewart, Ross

doi:10.1139/v87-291

Cited by 7 publications

(6 citation statements)

References 14 publications

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“…Venimadhavan et al (1989) have investigated catalysis of acetone enolization by various carboxylate anions, finding that ß for this reaction is 0.89. This group has also investigated acetone enolization catalysis by aryl phosphonate dianions (Shelly et al, 1987) for which ß = 0.72 and by alkyl phosphonate dianions (Shelly et al, 1990) for which ß = 0.83. Thus the value for ß which we have obtained for KSI enolization of 5-AND is similar to those of nonenzymatic systems studied so far.…”

Section: Discussionmentioning

confidence: 99%

Extent of Proton Transfer in the Transition States of the Reaction Catalyzed by the .DELTA.5-3-Ketosteroid Isomerase of Comamonas (Pseudomonas) testosteroni: Site-Specific Replacement of the Active Site Base, Aspartate 38, by the Weaker Base Alanine-3-sulfinate

Holman¹,

Benisek²

1994

Biochemistry

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Previous studies of the mechanism of the steroid isomerase of Comamonas (Pseudomonas) testosteroni have identified aspartate 38 as the proton porter which transfers the substrate's 4 beta proton to the 6 beta position of the product. Consequently, aspartate 38 functions as a base in the deprotonation of the substrate to form a dienol or dienolate intermediate, which then undergoes reprotonation from protonated aspartate 38 at C-6 beta to give the product. We have tried to characterize the transition states for the proton transfers by altering the pKa' of aspartate 38 and then determining the effect of the alteration on the kinetics of the enzyme. Alteration of the pKa' was accomplished by replacement of the carboxyl carbon of aspartate 38 by sulfur, a change which converts the carboxylate group to the much less basic sulfinate group. Employing Brønsted catalysis theory as applied to the individual steps of the isomerase mechanism, we find that in the enolization step of the reaction proton transfer to aspartate 38 is well advanced in the transition state. In the subsequent ketonization step, proton transfer from aspartate 38 has barely started when that transition state is reached. A series of mutant KSIs with alternative bases at position 38 have been constructed using a combination of site-directed mutagenesis and chemical modification: Asp-38 to Glu (D38E), His (D38H), and S-(carboxymethyl)cysteine (D38CMC). While the D38H and D38E mutants both retain significant isomerase activity, D38CMC is essentially inert. From the results of kinetic experiments it is possible to get a qualitative idea of the sensitivity of the enzyme's catalytic ability to the location of the base responsible for proton transfer.

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Section: Discussionmentioning

confidence: 99%

Extent of Proton Transfer in the Transition States of the Reaction Catalyzed by the .DELTA.5-3-Ketosteroid Isomerase of Comamonas (Pseudomonas) testosteroni: Site-Specific Replacement of the Active Site Base, Aspartate 38, by the Weaker Base Alanine-3-sulfinate

Holman¹,

Benisek²

1994

Biochemistry

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“…As part of a study of general acid and general base catalysis of protolytic reactions we have prepared a series of arylphosphonic acids, ArP03H2, and examined the effectiveness of the three catalytic species, ArP03H2, ArPO3HP, and AI-PO~'-, on the enolization of acetone (1); the present paper deals with the acid dissociation constants of the first two of these species.…”

Section: Introductionmentioning

confidence: 99%

Arylphosphonic acids. I. Substituent effects on their first and second dissociations

Nagarajan¹,

Shelly²,

Perkins³

et al. 1987

Can. J. Chem.

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, 1729 (1987) Thermodynamic pK1 and pK2 values of 36 arylphosphonic acids have been determined. The pK values of the tneta and para compounds are correlated well by the a " parameter, suggesting that there is little conjugation between the phosphonic group and the aromatic ring; the p values of the first and second dissociations are 0.923 and 1.140, respectively. The -P03H-group itself appears to be electron donating, contrary to earlier literature reports. The effect of ortho groups has been examined using multivariate analysis; the steric component of the proximity effect is acid weakening and has a larger effect on the second dissociation than on the first, presumably because a greater change in degree of solvation accompanies the second dissociation than the first.K. NAGARAJAN, KEVIN P. SHELLY, R. R. PERKINS et Ross STEWART. Can. J. Chem. 65, 1729 (1987). On a dtterrnint les valeurs des pKI et pKz thermodynamiques de 36 acides arylphosphoniques. On a pu ttablir une bonne corrklation entre les valeurs des pK des composts meta et para et le parametre a"; ce resultat suggkre qu'il existe peu de conjugation entre le groupement phosphonique et le cycle aromatique; les valeurs de p pour les premiere et deuxieme dissociations sont respectivement 0,923 et 1,140. Contrairement i ce qui a pu &tre publie anttrieurement, le groupement -P03HF semble &tre Clectrodonneur. Faisant appel a une analyse multi-variable, on a aussi examint I'effet des groupements en ortho; la composante stkrique de l'effet de proximitt a pour effet de diminuer l'aciditt et cet effet est plus important sur la deuxieme dissociation que sur la premiere; ce resultat est probablement caust par le fait que le changement dans le degrt de solvatation qui accompagne la deuxikme dissociation est plus important que celui qui accompagne la premikre.[Traduit par la revue] Introduction As part of a study of general acid and general base catalysis of protolytic reactions we have prepared a series of arylphosphonic acids, ArP03H2, and examined the effectiveness of the three catalytic species, ArP03H2, ArPO3HP, and AI-PO~'-, on the enolization of acetone (1); the present paper deals with the acid dissociation constants of the first two of these species.There are a number of reports in the literature of the effect of substituents on the pK1 and pK2 values of arylphosphonic acids, most notably those of Jaff6 et al. (2, 3) and of Nuallain (4). We are particularly concerned with proximity effects in prototropic reactions and we needed pK data for ortho, meta, and para derivatives. The data of Jaff6 et al. include such compounds but the pK values are not thermodynamic values; the data of Nuallain, which are much less extensive, have been corrected for ionic strength effects but include only two ortho compounds. Since we needed a set of self-consistent pK values for our catalytic work we have measured the first and second dissociation constants of a considerable number of arylphosphonic acids and corrected them to the standard state. The effects of substituents on t...

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“…Found: C, 68.75; , 9.01; N, 5.21. 0-(tert-Butyldimethylsilyl)crotonaldoxime (Id). To crotonaldehyde (1.2 mL, 15 mmol) and molecular sieves (5.7 g, 4 A)36 in CH2C12 (10 mL) in an ice bath was added a solution of (Mtert-butyldimethylsilybhydroxylamine37 (1.684 g, 11.44 mmol) in CH2C12 (3 mL). The reaction mixture was allowed to warm to room temperature and stirred for 24 h. The molecular sieves were removed through filtration, and the reaction mixture was concentrated in vacuo.…”

Section: Discussionmentioning

confidence: 99%

“…Caled for C2lH2oN20: C, 79.71; H, 6.37; N, 8.86. Found: C, 76.71; H, 6.46; N, 8.35. TV-Acetyl-1,2,3,4-tetrahydro-(2S *,3iZ MS *)-2-methyl-3,4diphenyl-6-cyanopyridine (14) and TV-Acetyl-1,2,3,4-tetrahydro-(2iZ*,3S,*,4S*)-2-methyl-3,4-diphenyl-6-cyanopyridine (15). A solution of 6 (267 mg, 1.35 mmol), ci's-/?-methylstyrene (1.5 mL, 11.56 mmol), and anhydrous benzene (3.5 mL) was refluxed.…”

Section: Discussionmentioning

confidence: 99%

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The N-acyl-.alpha.-cyano-1-azadienes. Remarkably reactive heterodienes in the Diels-Alder reaction

Teng¹,

Fowler²

1990

J. Org. Chem.

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A method for the prepartion of the N-acyl-a-cyano-1-azadienes has been developed and their Diels-Alder reactions have been studied. The intramolecular Diels-Alder reaction of these dienes with unactivated dienophiles occurs readily with a high preference for the exo (anti) reaction pathway. The JV-acyl-a-cyano-l-azadienes are relatively stable allowing for their isolation and an investigation of their intermolecular Diels-Alder reactions. The azadiene 6 reacted with a range of dienophiles such as, ethyl vinyl ether, styrene, 1-hexene, and methyl acrylate. The reaction of 6 with cis-and írarts-1-phenylpropene gave different products which was not consistent with a two-step reaction involving a common intermediate. The reactivity, regiochemistry, and stereochemistry of these reactions is interpreted in terms of a concerted mechanism with a transition state possessing a high degree of diradical character.

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Arylphosphonic acids. II. General acid and general base catalysis of acetone enolization

Cited by 7 publications

References 14 publications

Extent of Proton Transfer in the Transition States of the Reaction Catalyzed by the .DELTA.5-3-Ketosteroid Isomerase of Comamonas (Pseudomonas) testosteroni: Site-Specific Replacement of the Active Site Base, Aspartate 38, by the Weaker Base Alanine-3-sulfinate

Extent of Proton Transfer in the Transition States of the Reaction Catalyzed by the .DELTA.5-3-Ketosteroid Isomerase of Comamonas (Pseudomonas) testosteroni: Site-Specific Replacement of the Active Site Base, Aspartate 38, by the Weaker Base Alanine-3-sulfinate

Arylphosphonic acids. I. Substituent effects on their first and second dissociations

The N-acyl-.alpha.-cyano-1-azadienes. Remarkably reactive heterodienes in the Diels-Alder reaction

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