Steric course of lactonization in the deamination of glutamic acid: An organic mechanism experiment

Markgraf, J. Hodge; Davis, H. A.

doi:10.1021/ed067p173

Cited by 11 publications

(5 citation statements)

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“…All of the synthetic steps up until epoxide 37 were conducted following literature procedures. − Diazotization of 33 in 2 M HCl at 15 °C provided the (4 S )-(+)-4-carboxy-1,4-butyrolactone 34 in 98% yield. This was followed by reduction of the acid 34 with borane dimethyl sulfide complex (BMS) to provide the desired (4 S )-4-hydroxymethyl-4-butyrolactone 35 in 67% yield.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Azide-Alkyne Fragments for “Click” Chemical Applications. Part 2. Formation of Oligomers from Orthogonally Protected Chiral Trialkylsilylhomopropargyl Azides and Homopropargyl Alcohols

2009

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A small library of chiral, beta(3)-substituted homopropargyl alcohols and chiral beta(3)-substituted trimethylsilylhomopropargyl azides were generated starting from natural l-amino acids. The free alkynes and azides were then coupled, using a Huisgen 1,3-dipolar cycloaddition, to provide chiral oligomeric 1,4-disubstituted-1,2,3-triazoles as potential peptidomimetic compounds. The work is an extension to the previous synthesis of racemic, orthogonally protected 1,4-disubstituted-1,2,3-triazoles from the corresponding alpha-substituted propargyl alcohols and alpha-substituted trialkylsilylpropargyl azides.

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Section: Resultsmentioning

confidence: 99%

Synthesis of Azide-Alkyne Fragments for “Click” Chemical Applications. Part 2. Formation of Oligomers from Orthogonally Protected Chiral Trialkylsilylhomopropargyl Azides and Homopropargyl Alcohols

2009

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“…( S )-2HG was synthesized by a diazotization reaction, followed by alkaline hydrolysis. The diazotization of α-amino acids is considered to be a classic reaction for synthesizing α-hydroxy acids through the enantioselective route ( Brewster et al, 1950 ; Neuberger, 1948 ; Zollinger, 1995 ) involving a double-S N 2 mechanism on the α carbon ( Markgraf & Davis, 1990 ; Pleissner, Wimmer & Eriksen, 2011 ; Van Draanen & Hengst, 2010 ; Zollinger, 1995 ). In this work, we obtained ( S )-2HG from l -glutamic acid in a two-step procedure.…”

Section: Methodsmentioning

confidence: 99%

Effect of sodium (S)-2-hydroxyglutarate in male, and succinic acid in female Wistar rats against renal ischemia-reperfusion injury, suggesting a role of the HIF-1 pathway

Cienfuegos-Pecina

Ibarra‐Rivera

Saucedo

et al. 2020

PeerJ

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Background Ischemia–reperfusion (IR) injury is the main cause of delayed graft function in solid organ transplantation. Hypoxia-inducible factors (HIFs) control the expression of genes related to preconditioning against IR injury. During normoxia, HIF-α subunits are marked for degradation by the egg-laying defective nine homolog (EGLN) family of prolyl-4-hydroxylases. The inhibition of EGLN stabilizes HIFs and protects against IR injury. The aim of this study was to determine whether the EGLN inhibitors sodium (S)-2-hydroxyglutarate [(S)-2HG] and succinic acid (SA) have a nephroprotective effect against renal IR injury in Wistar rats. Methods (S)-2HG was synthesized in a 22.96% yield from commercially available L-glutamic acid in a two-step methodology (diazotization/alkaline hydrolysis), and its structure was confirmed by nuclear magnetic resonance and polarimetry. SA was acquired commercially. (S)-2HG and SA were independently evaluated in male and female Wistar rats respectively after renal IR injury. Rats were divided into the following groups: sham (SH), nontoxicity [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg], IR, and compound+IR [(S)-2HG: 12.5 or 25 mg/kg; SA: 12.5, 25, or 50 mg/kg]; independent SH and IR groups were used for each assessed compound. Markers of kidney injury (BUN, creatinine, glucose, and uric acid) and liver function (ALT, AST, ALP, LDH, serum proteins, and albumin), proinflammatory cytokines (IL-1β, IL-6, and TNF-α), oxidative stress biomarkers (malondialdehyde and superoxide dismutase), and histological parameters (tubular necrosis, acidophilic casts, and vascular congestion) were assessed. Tissue HIF-1α was measured by ELISA and Western blot, and the expression of Hmox1 was assessed by RT-qPCR. Results (S)-2HG had a dose-dependent nephroprotective effect, as evidenced by a significant reduction in the changes in the BUN, creatinine, ALP, AST, and LDH levels compared with the IR group. Tissue HIF-1α was only increased in the IR group compared to SH; however, (S)-2HG caused a significant increase in the expression of Hmox1, suggesting an early accumulation of HIF-1α in the (S)-2HG-treated groups. There were no significant effects on the other biomarkers. SA did not show a nephroprotective effect; the only changes were a decrease in creatinine level at 12.5 mg/kg and increased IR injury at 50 mg/kg. There were no effects on the other biochemical, proinflammatory, or oxidative stress biomarkers. Conclusion None of the compounds were hepatotoxic at the tested doses. (S)-2HG showed a dose-dependent nephroprotective effect at the evaluated doses, which involved an increase in the expression of Hmox1, suggesting stabilization of HIF-1α. SA did not show a nephroprotective effect but tended to increase IR injury when given at high doses.

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“…Chemical methods for deamination of amino acids may therefore be more appropriate. In one method, the amine moiety in the amino acid is converted first into a diazonium salt, from which gaseous nitrogen (N 2 ) can be eliminated in the presence of a reducing agent . For instance, glutaric acid was obtained in 88 % yield upon treating glutamic acid in a highly acidic aqueous medium with an excess of sodium nitrite and hypophosphoric acid (Scheme , route A) .…”

Section: Amino Acids As Direct Precursors To Value‐added Chemicalsmentioning

confidence: 99%

“… Direct deamination of glutamic acid to glutaric acid by using NaNO 2 and H 3 PO 2 in acidic media (route A) or hydroxylamine‐ O ‐sulfonic acid (NH 2 OSO 3 H) in basic media (route B) …”

Section: Amino Acids As Direct Precursors To Value‐added Chemicalsmentioning

confidence: 99%

Protein‐Rich Biomass Waste as a Resource for Future Biorefineries: State of the Art, Challenges, and Opportunities

et al. 2019

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Protein‐rich biomass provides a valuable feedstock for the chemical industry. This Review describes every process step in the value chain from protein waste to chemicals. The first part deals with the physicochemical extraction of proteins from biomass, hydrolytic degradation to peptides and amino acids, and separation of amino acid mixtures. The second part provides an overview of physical and (bio)chemical technologies for the production of polymers, commodity chemicals, pharmaceuticals, and other fine chemicals. This can be achieved by incorporation of oligopeptides into polymers, or by modification and defunctionalization of amino acids, for example, their reduction to amino alcohols, decarboxylation to amines, (cyclic) amides and nitriles, deamination to (di)carboxylic acids, and synthesis of fine chemicals and ionic liquids. Bio‐ and chemocatalytic approaches are compared in terms of scope, efficiency, and sustainability.

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Steric course of lactonization in the deamination of glutamic acid: An organic mechanism experiment

Abstract: The stereochemical consequences of a reaction at a chiral center offer a unique way to distinguish among mechanistic hypothesis.

Cited by 11 publications

References 2 publications

Synthesis of Azide-Alkyne Fragments for “Click” Chemical Applications. Part 2. Formation of Oligomers from Orthogonally Protected Chiral Trialkylsilylhomopropargyl Azides and Homopropargyl Alcohols

Synthesis of Azide-Alkyne Fragments for “Click” Chemical Applications. Part 2. Formation of Oligomers from Orthogonally Protected Chiral Trialkylsilylhomopropargyl Azides and Homopropargyl Alcohols

Effect of sodium (S)-2-hydroxyglutarate in male, and succinic acid in female Wistar rats against renal ischemia-reperfusion injury, suggesting a role of the HIF-1 pathway

Protein‐Rich Biomass Waste as a Resource for Future Biorefineries: State of the Art, Challenges, and Opportunities

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