2889-31-8Relevant articles and documents
Pyruvate Aldolases Catalyze Cross-Aldol Reactions between Ketones: Highly Selective Access to Multi-Functionalized Tertiary Alcohols
De Berardinis, Véronique,Gefflaut, Thierry,Gourbeyre, Léa,Guérard-Hélaine, Christine,Hélaine, Virgil,Laurent, Victor,Lemaire, Marielle,Nauton, Lionel,Salanoubat, Marcel,Tra?kia, Mounir,Uzel, Alexandre
, p. 2538 - 2543 (2020)
Tertiary alcohols are widely represented in nature and among bioactive molecules. Their importance is attested by the continuous efforts to meet the challenge of their stereoselective synthesis. In this context, we propose an enzymatic approach, involving class II pyruvate aldolases. These enzymes are shown to catalyze selective cross-aldol reactions between pyruvic acid or derivatives as nucleophiles and a series of ketones as electrophiles. This catalytic activity is exemplified by the highly stereoselective preparation of seven branched ketols with good yields. One of them was readily converted into a constrained 4-hydroxyproline analogue in a multienzymatic one-pot one-step process.
FLAVIN-MEDIATED PHOTOLYSIS OF MYCOSPORINES
Bernillon, Jacques,Parussini, Ermis,Letoublon, Robert,Favre-Bonvin, Jean,Arpin, Noel
, p. 81 - 84 (1990)
Under aerobic conditions and in the presence of flavins, light causes the photolysis of mycosporine glutamine into aminocyclohexenone and 2-hydroxy glutaric acid.This photolysis, which is temperature dependent, is also observed when other photosensitizers which are carriers of singlet oxygen replace flavins.This photodestruction also occurs with mycosporine amino alcohols but at reduced rate and probably by another mechanism.
Metal-catalyzed reductive deamination of glutamic acid to bio-based dimethyl glutarate and methylamines
De Schouwer, Free,Cuypers, Thomas,Claes, Laurens,De Vos, Dirk E.
, p. 1866 - 1876 (2017/06/09)
Glutamic acid is a promising renewable platform molecule which is abundantly available in biomass waste streams; it is also efficiently manufactured by fermentation. Here we report the reductive deamination of glutamic acid to bio-based dimethyl glutarate and methylamines. In order to recycle nitrogen in an industrially relevant co-product, glutamic acid was modified to N,N-dimethylglutamic acid by a mild reductive alkylation with Pd/C. Subsequently, selective C-N hydrogenolysis in methanol resulted in dimethyl glutarate and trimethylamine. A wide screening of transition metals (Pt, Pd, Rh and Ru) immobilized on various supports showed that the highest yields of dimethyl glutarate were obtained with Pt/TiO2. An FTIR study and kinetic experiments on metal-loaded and unloaded supports demonstrate that the interplay between the metal and the moderate acidity of the support results in the excellent C-N hydrogenolysis activity and selectivity. Finally, reaction parameter optimization resulted in 81% yield of dimethyl glutarate with 1 wt% Pt/TiO2 at 225 °C, 30 bar H2 after 8 h.
Acidic pH is a metabolic switch for 2-Hydroxyglutarate generation and signaling
Sergiy, M. Nadtochiy,Xenia, Schafer,Dragony, Fu,Keith, Nehrke,Joshua, Munger,Brookes, Paul S.
, p. 20188 - 20197 (2016/11/03)
2-Hydroxyglutarate (2-HG) is an important epigenetic regulator, with potential roles in cancer and stem cell biology. The D-(R)-enantiomer (D-2-HG) is an oncometabolite generated from α-ketoglutarate (α-KG) by mutant isocitrate dehydrogenase, whereas L-(S)-2-HG is generated by lactate dehydrogenase and malate dehydrogenase in response to hypoxia. Because acidic pH is a common feature of hypoxia, as well as tumor and stem cell microenvironments, we hypothesized that pH may regulate cellular 2-HG levels. Herein we report that cytosolic acidification under normoxia moderately elevated 2-HG in cells, and boosting endogenous substrate α-KG levels further stimulated this elevation. Studies with isolated lactate dehydrogenase-1 and malate dehydrogenase-2 revealed that generation of 2-HG by both enzymes was stimulated severalfold at acidic pH, relative to normal physiologic pH. In addition, acidic pH was found to inhibit the activity of the mitochondrial L-2-HG removal enzyme L-2-HG dehydrogenase and to stimulate the reverse reaction of isocitrate dehydrogenase (carboxylation of α-KG to isocitrate). Furthermore, because acidic pH is known to stabilize hypoxia-inducible factor (HIF) and 2-HG is a known inhibitor of HIF prolyl hydroxylases, we hypothesized that 2-HG may be required for acid-induced HIF stabilization. Accordingly, cells stably overexpressing L-2-HG dehydrogenase exhibited a blunted HIF response to acid. Together, these results suggest that acidosis is an important and previously overlooked regulator of 2-HG accumulation and other oncometabolic events, with implications for HIF signaling.
