Asymmetric Methyl Groups: Preparation and Detection of Chiral Methyl Groups

Luthy, James A.; Rétey, János; Arigoni, D.

doi:10.1038/2211213a0

Cited by 176 publications

(84 citation statements)

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“…The chirality of the asymmetric methyl groups was determined by the use of two enzymes catalysing reactions of known stereochemical course. (8) at C-2 of acetate [18,19,22]. Fumarase catalyses the equilibration of the C-3 pro-R hydrogen of malate with the protons of the medium [20,21] The simplest mechanism to achieve this inversion is an S N~ type of displacement of the amino group by hydride.…”

Section: Discussionmentioning

confidence: 99%

“…Incubations were terminated after only 10 min to ensure that any labilisation of hydrogen was minimal. In each case the biosynthetic acetic acid (about 0.5 pmol) was isolated by lyophilisation and subjected to chirality analysis by the method of Cornforth et al [I81 and Luthy et al [19]. This involved the conversion of acetic acid in situ to acetyl phosphate, acetyl-CoA and then (2s)-malate.…”

Section: Generation and Analysis Of' Chiral Acetatesmentioning

confidence: 99%

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Mechanistic and Stereochemical Studies on the Glycine Reductase of Clostridium sticklandii

Barnard

Akhtar

1979

European Journal of Biochemistry

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Clostridial glycine reductase multienzyme complex which catalyses the reaction :Glycine + ADP + Pi + 2H -+ Acetate + ATP + NH3 was solubilised and fractionated essentially according to the method of Stadtman [T. C. Stadtman (1970) Methods Enzymol. I7A, 956 -9661 into two components : protein A and 'glycine reductase' fraction. A reconstituted system obtained by combining the two components in the presence of dithiothreitol catalysed the conversion of glycine into acetate concomitant with the phosphorylation of ADP to ATP. Using the reconstitued system, in which the unwanted enzymic activity catalyzing an exchange of the ct hydrogen atoms of glycine with the protons of the medium had been greatly reduced, it was found that the conversion of (2RS)-[2-14C, 2-3H1]glycine (3H/'4C = 7.16) into acetate (3H/14C = 7.03) was attended by the retention of both the C-2 hydrogen atoms of glycine. Conversion of (2S)-[2-2H1, 2-3Hl]glycine and (2R)-[2-2H1, 2-3Hl]glycine by the reconstituted system gave (2S)-acetate and (2R)-acetate respectively showing that the reductive deamination of glycine occurs through an inversion of configuration. The cumulative information available on the glycine reductase reaction is embodied in a hypothetical mechanism of action for the enzyme.

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Section: Discussionmentioning

confidence: 99%

Section: Generation and Analysis Of' Chiral Acetatesmentioning

confidence: 99%

Mechanistic and Stereochemical Studies on the Glycine Reductase of Clostridium sticklandii

Barnard

Akhtar

1979

European Journal of Biochemistry

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“…The neutralized supernatant, containing the chiral acetyl-CoA, was used as substrate in the malate synthase reaction together with glyoxylate. The malic acid so produced was isolated by dilution with carrier malic acid and the steric distribution of tritium in the malic acid so obtained was determined as previously described [5,6]. The results are compiled in Table 1 …”

Section: Prepuraiion Of (1r)-and Of ( I S ) -( I-'h)( L-'h]friicfostmentioning

confidence: 99%

Stereochemical Investigation of the Phosphoketolase Reaction

Merkler

Rétey

1981

European Journal of Biochemistry

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“…Consequently, the reaction, carried out in a sealed tube, proceeded with very low yield, 0.4-1% based on tritiated aldehyde, but did produce suffi cient amounts of acetic acid for configurational analysis. The two acetate samples were isolated and purified by steam distillation and subjected to en zymatic chirality analysis of the methyl group by the method of Cornforth [18] and Arigoni [19], using a procedure routinely employed in our laboratory [20]. This method of analysis involves activation of acetate to acetyl-coenzyme A followed by condensation with glyoxylate, catalyzed by malate synthase, to give malate.…”

Section: -Methy Ipentanoic Acidmentioning

confidence: 99%

Steric Course of the Rhodium-Catalyzed Decarbonylation of Chiral 4-M ethyl-[1-³H,2-²H₁]pentanal

Otsuka

Floss

1987

Zeitschrift Für Naturforschung C

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Dedicated to Professor Helmut Simon on the occasion o f his 60th birthdayStereochemistry, Decarbonylation, Rhodium Catalyst, Chiral Methyl Group, 4-Methylpentanal (R)-and (5)-4-methyl-[l-3H,2-2H!]pentanal were prepared from l -and D-leucine via leucic acid and (S)-and (ft)-4-methyl-[2-2H,]pentanoic acid. Decarbonylation of these samples with tris-(triphenylphosphine)rhodium chloride followed by Kuhn-Roth oxidation of the resulting 2-methylbutane gave chiral acetic acid of 35% e.e. S and 31% e.e. R configuration, respectively. The decarbonylation reaction thus proceeds with net retention of configuration, possibly accom panied by some racemization.The stereochemistry of the decarbonylation of aldehydes catalyzed by tris-(triphenylphosphine)rhodium chloride has been examined in a few cases [1]. The reaction was found to proceed with high stereoselectivity, except when the a-carbon car ried an electron-donating group like -OCH3, and net retention of configuration. However, all the cases studied involved hindered aldehydes in which the formyl group was attached to a quaternary car bon. In the analogous decarbonylation of acid chlorides [2, 3] net retention of configuration was also observed, but these reactions were accompanied by a high degree of racemization. However, the cases studied here also involved less crowded systems in which the carbonyl group was attached to a primary or secondary carbon. These reactions represent the reversal of the so-called carbonyl insertions into transition metal-carbon bonds [4], which, mechanis tically, are actually migrations of a metal-bound alkyl group to an adjacent bound carbon monoxide. These, in the cases studied, also proceed with reten tion of configuration of the alkyl group [5, cf. 4, 6, 7].In the course of studies on stereochemical aspects of the biosynthesis of ergot alkaloids [8] we were faced with the problem of determining the configura tion of 4-methylpentanoic acid stereospecifically monodeuterated at C-2 on ^g samples obtained in an impure state from complex reaction mixtures. It oc curred to us that the limitation of quantity could be overcome by converting the acid to the 1-tritiated alcohol by reduction with tritiated LiBH4, followed by oxidation to the aldehyde and decarbonylation to give 2-methylbutane carrying a chiral methyl group at C-4 (Scheme I). In this sequence the tritiated, deuterated alcohol could be diluted with ample car rier material, allowing the subsequent chemical steps to be carried out on a more manageable scale.To explore the feasibility of this degradation se quence it was necessary to determine whether the decarbonylation of an uncrowded aldehyde like 4-methylpentanal also proceeds stereospecifically with retention of configuration. The results are reported here because of the current interest in an important biochemical carbonyl insertion reaction, the synthe sis of acetic acid in anaerobic organisms [9], and its stereochemistry [10]. ResultsTo examine the steric course of the transition metal-catalyzed decarbonylation of 4-methylpenta...

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Asymmetric Methyl Groups: Preparation and Detection of Chiral Methyl Groups

Cited by 176 publications

References 10 publications

Mechanistic and Stereochemical Studies on the Glycine Reductase of Clostridium sticklandii

Mechanistic and Stereochemical Studies on the Glycine Reductase of Clostridium sticklandii

Stereochemical Investigation of the Phosphoketolase Reaction

Steric Course of the Rhodium-Catalyzed Decarbonylation of Chiral 4-M ethyl-[1-³H,2-²H₁]pentanal

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Asymmetric Methyl Groups: Preparation and Detection of Chiral Methyl Groups

Cited by 176 publications

References 10 publications

Mechanistic and Stereochemical Studies on the Glycine Reductase of Clostridium sticklandii

Mechanistic and Stereochemical Studies on the Glycine Reductase of Clostridium sticklandii

Stereochemical Investigation of the Phosphoketolase Reaction

Steric Course of the Rhodium-Catalyzed Decarbonylation of Chiral 4-M ethyl-[1-3H,2-2H1]pentanal

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Steric Course of the Rhodium-Catalyzed Decarbonylation of Chiral 4-M ethyl-[1-³H,2-²H₁]pentanal