120085-62-3Relevant academic research and scientific papers
Substituted glycals as probes of glycosidase mechanisms
Lai, Ellen C. K.,Morris, Sandra A.,Street, Ian P.,Withers, Stephen G.
, p. 1929 - 1937 (1996)
D-Glucal and a series of substituted derivatives have been tested as substrates, inhibitors and inactivators of the Agrobacterium faecalis β-glucosidase in order to probe structure/function relationships in this enzyme. D-Glucal is shown to be a substrate (k(cat) = 2.3 min-1, K(m) = 0.85 mM) undergoing hydration with stereospecific protonation from the α-face to yield 2-deoxy-β-D-glucose. 1-Methyl-D-glucal surprisingly serves as only a poor substrate (k(cat) = 0.056 min-1, K(m) = 57 mM), also undergoing protonation from the α-face. 2-Fluoro-D-glucal, however, is completely inert, as a result of inductive destabilisation of the oxocarbenium ion-like transition state for protonation, and functions only as a relatively weak (K(i) = 24 mM) inhibitor. Similar behaviour was seen with almond β-glucosidase and yeast α-glucosidase and for the interaction of 2-fluoro-D-galactal with Escherichia coli β-galactosidase. A series of α,β-unsaturated glucal derivatives was also synthesised and tested as potential substrates, inhibitors or inactivators of A. faecalis β-glucosidase. Of these only 1-nitro-D-glucal functioned as a time dependent, irreversible inactivator (k(i) = 0.011 min-1, K(i) = 5.5 mM), presumably acting as a Michael acceptor. Electrospray mass spectrometric analysis revealed multiple labeling of the enzyme by this inactivator, lessening its usefulness as an affinity label. Less reactive Michael acceptor glycals which might have been more specific (1-cyano-, 2-cyano-, 1-carboxylic acid, 1-carboxylic acid methyl ester) unfortunately did not function as inactivators or substrates, only as relatively weak reversible inhibitors (K(i) = 3-96 mM).
A novel chemical synthesis of a 3-deoxy-D-arabino-heptulosonic acid 7-phosphate (DAHP) derivative and its 2-deoxy analogue
Mlynarski, Jacek,Banaszek, Anna
, p. 69 - 75 (2007/10/03)
Using 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl cyanide as a precursor, methyl (methyl 3-deoxy-α-D-arabino-hept-2-ulopyranosid)onate (6) and its 2-deoxy analogue (10) were prepared. The synthesis involved an elimination of one molecule of acetic acid from C-2-C-3 and transformation of the CN group into COOMe, followed by methoxymercuration with subsequent reductive removal of the mercuri residue to give 6 or hydrogenation of the double bond to give 10. Phosphorylation of the 7-OH group led to the title compounds.
Synthesis of C-Glycosyltetrazoles Related to 3-Deoxy-D-arabino-heptulosonic Acid 7-Phosphate (DHAP); Potential Inhibitors of Early Steps in the Shikimate Pathway
Buchanan, J. Grant,Clelland, Andrew P. W.,Johnson, Trevor,Rennie, Robert A. C.,Wightman, Richard H.
, p. 2593 - 2602 (2007/10/02)
Treatment of 3,4,5,7-tetra-O-acetyl-2,6-anhydro-D-glycero-D-galacto-heptononitrile 16 with diazabicycloundecene (DBU) formed 4,5,7-tri-O-acetyl-2,6-anhydro-3-deoxy-D-arabino-hept-2-enononitrile 22, which on treatment with ammonium azide gave the corresponding unsaturated tetrazole 23.Stereoselective catalytic reduction of 23 and subsequent deacetylation produced 5-(2-deoxy-β-D-arabino-hexopyranosyl)tetrazole 24, which was converted in two steps into its 6-phosphate 10.Reaction of 4,5,7-tri-O-acetyl-2,6-anhydro-3-deoxy-D-manno-heptononitrile 27 with ammonium azide, followed by deacetylation, gave 5-(2-deoxy-α-D-arabino-hexopyranosyl)tetrazole 29 (81percent overall), which was converted into its 6-phosphate 11.When 4,5,7-tri-O-acetyl-2,6-anhydro-2-bromo-3-deoxy-D-gluco-heptononitrile 31 was treated with methanol and 2,6-lutidine, methyl 3,4,6-tri-O-acetyl-1-cyano-2-deoxy-β-D-arabino-hexopyranoside 34 was obtained (40percent) together with the α-anomer 35 (11percent).Cycloaddition of 34 with azide ion, followed by sequential treatment with base and with acid, gave 2-deoxy-1-tetrazol-5-yl-α-D-arabino-hexopyranose 12 (54percent overall).Treatment of 1,3,4,6-tetra-O-acetyl-2-deoxy-α-D-lyxo-hexopyranose 38 with trimethylsilyl cyanide and boron trifluoride in nitromethane gave 4,5,7-tri-O-acetyl-2,6-anhydro-3-deoxy-D-talo-heptononitrile 40 (53percent), together with the D-galacto-epimer 39 (17percent).Cycloaddition of 39 and 40 with azide ion and subsequent deprotection gave 5-(2-deoxy-β-D-lyxo-hexopyranosyl)tetrazole 13 and the α-D-lyxo-isomer 14 respectively in good yields.Reaction of nitrile 40 with N-bromosuccinimide formed 4,5,7-tri-O-acetyl-2,6-anhydro-2-bromo-3-deoxy-D-galacto-heptononitrile 43 (63percent), which with methanol and 2,6-lutidine was converted into the methyl β-D-glycoside 44.Cycloaddition of 44 with azide ion, deacetylation, and hydrolysis led to 2-deoxy-1-tetrazol-5-yl-α-D-lyxo-hexopyranose 15.None of the C-glycosyltetrazoles were strong inhibitors of dehydroquinate synthase from E.coli.
Preparation of 2,6-Anhydro-3-deoxyhept-(or hex-)2-enononitriles (1-Cyanoglycals) from 1-Bromo-D-glycosyl Cyanides with Zinc under Aprotic Conditions
Somsak, Laszlo,Bajza, Istvan,Batta, Gyula
, p. 1265 - 1268 (2007/10/02)
Acetylated 1-bromo-D-glycosyl cyanides 1 - 5 react with zinc dust in acetic acid, acetic acid/water, or 2-propanol to give mixtures of acetylated 1-cyanoglycals 6-9 and anomeric pairs of glycosyl cyanides 10-14.Reaction of 1-5 in refluxing benzene in the presence of one equivalent of triethylamine or especially pyridine predominantly leads to the formation of 1-cyanoglycals.
