154461-26-4Relevant articles and documents
Both d - And l -Glucose Polyphosphates Mimic d - myo-Inositol 1,4,5-Trisphosphate: New Synthetic Agonists and Partial Agonists at the Ins(1,4,5)P3Receptor
Shipton, Megan L.,Riley, Andrew M.,Rossi, Ana M.,Brearley, Charles A.,Taylor, Colin W.,Potter, Barry V. L.
, p. 5442 - 5457 (2020)
Chiral sugar derivatives are potential cyclitol surrogates of the Ca2+-mobilizing intracellular messenger d-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. Six novel polyphosphorylated analogues derived from both d- and l-glucose were synthesized. Binding to Ins(1,4,5)P3 receptors [Ins(1,4,5)P3R] and the ability to release Ca2+ from intracellular stores via type 1 Ins(1,4,5)P3Rs were investigated. β-d-Glucopyranosyl 1,3,4-tris-phosphate, with similar phosphate regiochemistry and stereochemistry to Ins(1,4,5)P3, and α-d-glucopyranosyl 1,3,4-tris-phosphate are full agonists, being equipotent and 23-fold less potent than Ins(1,4,5)P3, respectively, in Ca2+-release assays and similar to Ins(1,4,5)P3 and 15-fold weaker in binding assays. They can be viewed as truncated analogues of adenophostin A and refine understanding of structure-activity relationships for this Ins(1,4,5)P3R agonist. l-Glucose-derived ligands, methyl α-l-glucopyranoside 2,3,6-trisphosphate and methyl α-l-glucopyranoside 2,4,6-trisphosphate, are also active, while their corresponding d-enantiomers, methyl α-d-glucopyranoside 2,3,6-trisphosphate and methyl α-d-glucopyranoside 2,4,6-trisphosphate, are inactive. Interestingly, both l-glucose-derived ligands are partial agonists: they are among the least efficacious agonists of Ins(1,4,5)P3R yet identified, providing new leads for antagonist development.
Synthesis of the monosaccharide units of the O-specific polysaccharide of Shigella sonnei
Medgyes, Adel,Farkas, Erzsebet,Liptak, Andras,Pozsgay, Vince
, p. 4159 - 4178 (2007/10/03)
The monosaccharide components of the O-specific polysaccharide 1 of the lipopolysaccharide of the enteropathogenic bacterium Shigella sonnei were synthesized as their methyl glycosides 2 and 3 in their natural anomeric form. The key intermediate to the diaminotrideoxygalactose derivative 2 was ethyl-3-O-acetyl-2-deoxy-2-phthalimido-1-thio-β-D- glucopyranoside (9) that was converted to its ditosylate 10. Regioselective deoxygenation at C-6 followed by nucleophilic displacement of the secondary tosyloxy group by azide afforded the 4-azido thioglycoside 13. Methyl trifluoromethanesulfonate-assisted methanolysis of 13 gave the O-glycoside 14. Replacement of the phthalimido by an acetamido group followed by catalytic reduction of the azido group led to the diamino-trideoxygalactose derivative 2. The precursor to the L-altruronic acid derivative 3 was methyl α-L-glucopyranoside (19) that was routinely converted to the benzylidene-protected 2,3-anhydro-allopyranoside 22. Regioselective opening of the epoxide ring by NaN3 afforded the 2-azido derivative 23 that was benzylated at HO-3. Hydrolytic removal of the benzylidene group followed by TEMPO oxidation of C-6 and subsequent esterification with MeI gave the key L-azido-altruronic acid intermediate 29 that was transformed to the acetamido-altruronic acid derivative 3. High resolution NMR data of the altruronic acid derivatives indicate that the conformation of their pyranose ring is crucially dependent on the substitution pattern: the 2-azido altruronic acid derivatives prefer the 4C1 conformation whereas the 2-acetamido congeners exist preferentially in the 1C4 conformation.
