55601-64-4

Upstream product

• 98140-16-0 2-chloro-4-methyl-glutaric acid 
• 107987-03-1 diethyl 4-methyl-2-oxopentanedioate 
• 5464-46-0 diethyl 3-ethoxycarbonyl-4-methyl-2-oxopentanedioate 
• 22727-82-8 1-oxo-butane-1,2,4-tricarboxylic acid triethyl ester 
• 42998-61-8 Dimethyl 4-methyl-2-oxopentanedioate 
• 32980-25-9 2-methylsuccinic acid 1-methyl ester 

Downstream Products

• 31137-74-3 (2S,4R)-4-methylglutamic acid 
• 6141-27-1 (2S,4S)-4-methylglutamic acid 
• 2596-04-5 (2S)-4-methylglutamic acid 
• 108050-02-8 1-(4-nitrobenzyl) 4-methyl-2-oxoglutarate 

Relevant academic research and scientific papers

Synthesis of 2-oxoglutarate derivatives and their evaluation as cosubstrates and inhibitors of human aspartate/asparagine-β-hydroxylase

2-Oxoglutarate (2OG) is involved in biological processes including oxidations catalyzed by 2OG oxygenases for which it is a cosubstrate. Eukaryotic 2OG oxygenases have roles in collagen biosynthesis, lipid metabolism, DNA/RNA modification, transcriptional regulation, and the hypoxic response. Aspartate/asparagine-β-hydroxylase (AspH) is a human 2OG oxygenase catalyzing post-translational hydroxylation of Asp/Asn-residues in epidermal growth factor-like domains (EGFDs) in the endoplasmic reticulum. AspH is of chemical interest, because its Fe(ii) cofactor is complexed by two rather than the typical three residues. AspH is upregulated in hypoxia and is a prognostic marker on the surface of cancer cells. We describe studies on how derivatives of its natural 2OG cosubstrate modulate AspH activity. An efficient synthesis of C3- and/or C4-substituted 2OG derivatives, proceedingviacyanosulfur ylid intermediates, is reported. Mass spectrometry-based AspH assays with >30 2OG derivatives reveal that some efficiently inhibit AspHviacompeting with 2OG as evidenced by crystallographic and solution analyses. Other 2OG derivatives can substitute for 2OG enabling substrate hydroxylation. The results show that subtle changes,e.g.methyl- to ethyl-substitution, can significantly alter the balance between catalysis and inhibition. 3-Methyl-2OG, a natural product present in human nutrition, was the most efficient alternative cosubstrate identified; crystallographic analyses reveal the binding mode of (R)-3-methyl-2OG and other 2OG derivatives to AspH and inform on the balance between turnover and inhibition. The results will enable the use of 2OG derivatives as mechanistic probes for other 2OG utilizing enzymes and suggest 2-oxoacids other than 2OG may be employed by some 2OG oxygenasesin vivo.

Chemoenzymatic synthesis of optically active 4-methyl-tetrahydro-5-oxo- 2-furancarboxylic acids and esters

Enantiomerically pure 4-methyl-tetrahydro-5-oxo-2-furancarboxylic acids and esters are prepared by enzymatic resolution of the chiral racemic esters. Their stereochemistry as well as their absolute configurations have been established by chemical correlation. The influence of the alkoxycarbonyl group at C-2 and that of the methyl group at C-4 on the sign of the Cotton effect in their CD spectra have been investigated. Formation of enantiomerically pure hydroxydiesters, precursors of the above-mentioned γ- lactones, by baker's yeast reduction of the corresponding ketodiesters was unsatisfactory. (C) 2000 Elsevier Science Ltd.