Syntheses of (2S,3R)- and (2S,3S)-3-methylglutamic acid

Hartzoulakis, Basil; Gani, David

doi:10.1039/p19940002525

Cited by 22 publications

(20 citation statements)

References 9 publications

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“…Rearrangement of 480 and hydrolysis afforded (2S,3R)-3-methylglutamic acid (481) which served to probe the mechanism of glutamate-utilizing enzymes (Scheme 57). [354] -α-aminoadipic acid (485) was synthesized from -glutamic acid by applying the ArndtϪEistert protocol to 482. [355] A similar route led to α-(methylamino)adipic acid.…”

Section: Homologation Of α-Amino Acidsmentioning

confidence: 99%

100 Years of the Wolff Rearrangement

2002

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The conversion of α‐diazo ketones into ketenes, and products derived therefrom, was discovered by Wolff in 1902. Major applications of the Wolff rearrangement, such as the Arndt−Eistert reaction (homologation of carboxylic acids) and the ring contraction of cyclic ketones, have been with us for some while. Nevertheless, substantial progress has been made recently. The reaction mechanism has been explored by means of matrix isolation, time‐resolved spectroscopy, and computation. Full retention of configuration of the migrating group has been established by using enantioselective chromatography. The Arndt−Eistert reaction has witnessed a renaissance in the field of natural products, in particular β‐amino acids and β‐peptides. Ring‐contracting Wolff rearrangements and ketene cycloadditions have been applied in syntheses of increasingly complex, biologically active target molecules. These accomplishments, as well as unsolved problems, are addressed in the present review. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

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Section: Homologation Of α-Amino Acidsmentioning

confidence: 99%

100 Years of the Wolff Rearrangement

2002

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“…[2] Of the selective and catalytic reactions involving carbon dioxide as a C-1 building block for the synthesis of fine chemicals, electrochemical methods have been shown to have a wide range of applications. [3] The fixation of CO 2 into organic substrates may involve its reactivity in nucleophilic reactions [5] or its activation by coordination to low-valent transition metal complexes. [3] The fixation of CO 2 into organic substrates may involve its reactivity in nucleophilic reactions [5] or its activation by coordination to low-valent transition metal complexes.…”

Section: Introductionmentioning

confidence: 99%

Electrochemical Selective Incorporation of CO2 into Terminal Alkynes and Diynes

Köster¹,

Dinjus

Duñach

2001

Eur. J. Org. Chem.

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“…It is one of a group of enzymes that use adenosylcobalamin (AdoCbl), 1 a biologically active form of vitamin B 12 , to catalyze unusual 1,2-rearrangements in which an electron-withdrawing group is interchanged with a hydrogen atom on an adjacent carbon (4 -6) The migrating group may be -OH, -NH 2 , or, as in the case of glutamate mutase, a carbon-containing fragment so that a skeletal rearrangement is effected (Fig. 1).…”

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confidence: 99%

The Reaction of the Substrate Analog 2-Ketoglutarate with Adenosylcobalamin-dependent Glutamate Mutase

Roymoulik

Chen

Marsh

1999

Journal of Biological Chemistry

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Glutamate mutase is one of several adenosylcobalamindependent enzymes that catalyze unusual rearrangements that proceed through a mechanism involving free radical intermediates. The enzyme exhibits remarkable specificity, and so far no molecules other than L-glutamate and L-threo-3-methylaspartate have been found to be substrates. Here we describe the reaction of glutamate mutase with the substrate analog, 2-ketoglutarate. Binding of 2-ketoglutarate (or its hydrate) to the holoenzyme elicits a change in the UV-visible spectrum consistent with the formation of cob(II)alamin on the enzyme. 2-ketoglutarate undergoes rapid exchange of tritium between the 5-position of the coenzyme and C-4 of 2-ketoglutarate, consistent with the formation of a 2-ketoglutaryl radical analogous to that formed with glutamate. Under aerobic conditions this leads to the slow inactivation of the enzyme, presumably through reaction of free radical species with oxygen. Despite the formation of a substrate-like radical, no rearrangement of 2-ketoglutarate to 3-methyloxalacetate could be detected. The results indicate that formation of the C-4 radical of 2-ketoglutarate is a facile process but that it does not undergo further reactions, suggesting that this may be a useful substrate analog with which to investigate the mechanism of coenzyme homolysis.Glutamate mutase catalyzes the reversible isomerization of L-glutamate and L-threo-3-methylaspartate (1-3). It is one of a group of enzymes that use adenosylcobalamin (AdoCbl), 1 a biologically active form of vitamin B 12 , to catalyze unusual 1,2-rearrangements in which an electron-withdrawing group is interchanged with a hydrogen atom on an adjacent carbon (4 -6) The migrating group may be -OH, -NH 2 , or, as in the case of glutamate mutase, a carbon-containing fragment so that a skeletal rearrangement is effected (Fig. 1). The role of AdoCbl as the source of carbon-based radicals, which are unmasked by homolysis of the coenzyme cobalt-carbon bond, is well established (7). Experiments with isotopically labeled substrates and coenzyme have demonstrated that for all the enzymes examined including glutamate mutase, 5Ј-deoxyadenosine acts as the intermediate carrier of the migrating hydrogen (8, 9).Recently, we have shown that in glutamate mutase homolysis of the cobalt-carbon bond and hydrogen abstraction from the substrate are kinetically coupled processes (10). Adenosyl radical can therefore only be formed as a transient high energy species, or may not be formed at all if coenzyme homolysis and hydrogen abstraction are truly concerted processes. Similar findings have been reported for the related AdoCbl-dependent enzyme, methylmalonyl-CoA mutase (11). These unexpected observations have focused our attention on the role of the substrate in initiating free radical formation. A further intriguing and poorly understood aspect of these reactions is how the enzyme controls the rearrangement of substrate-radical to product-radical.In principle, these steps might be probed with substrates that give rise ...

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Syntheses of (2S,3R)- and (2S,3S)-3-methylglutamic acid

Cited by 22 publications

References 9 publications

100 Years of the Wolff Rearrangement

100 Years of the Wolff Rearrangement

Electrochemical Selective Incorporation of CO2 into Terminal Alkynes and Diynes

The Reaction of the Substrate Analog 2-Ketoglutarate with Adenosylcobalamin-dependent Glutamate Mutase

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