Effect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases

A fast, efficient and stereoselective synthesis of hydroxy-pyrrolidines

“…However, unlike most other iodo-pentofuranosides, 18 literature precedent for the formation of the iodinated methyl glycoside 13 involved either a six-step synthesis commencing with D-mannose 23 or a five-step synthesis from 1,2-O-cyclohexylidene-a-Dxylofuranose. 24 Being keen to develop a shorter, and potentially more efficient synthesis, we subjected D-lyxose (11) to a solution of AcCl in MeOH and stirred the reaction for 18 h at room temperature (Scheme 3). Though a sometimes fickle reaction, 25 with the major impediment being the formation of the undesired thermodynamically more stable methyl pyranoside, these conditions nevertheless lead to the formation of the desired methyl glycoside 12 in 87% yield (with 8% of the pyranose isomer).…”

“…1). Of these pyrrolidines, 1,4-dideoxy-1,4-imino-D-xylitol (1), isolated from the Pteridophyte Arachniodes standishii, 10 is a weak glycogen phosphorylase b inhibitor, 11 while its L-isomer, 1,4-dideoxy-1,4-imino-L-xylitol (2), and (3), are yet to be isolated or tested for biological activity. Of the lyxitol pyrrolidines, 1,4-dideoxy-1,4-imino-D-lyxitol (4), the structure tentatively assigned to a pyrrolidine found from Raispalia sp., 12 is a potent a-galactosidase inhibitor, 13,14 while 1,4-dideoxy-1,4-imino-L-lyxitol (5) has not been isolated or assayed.…”

Sugar-mimicking glycosidase inhibitors: bioactivity and application

“…A combination of a potent GP inhibitor and a potent debranching enzyme inhibitor might be more effective for inhibition of glycogen breakdown. D-AB1 and DNJ are potent inhibitors of GP and 1,6-GL, with IC 50 values of 0.43 and 0.19 mM, respectively [35,42]. D-AB1 inhibited glucagon-stimulated glucose production dose-dependently with an IC 50 value of 9 mM, whereas administration of DNJ reached a plateau at 100 mM with 25 % inhibition and then remained unchanged, as shown in Figure 4 [42].…”

“…3.16) completely abolished its inhibition of GP, showed no inhibition of the enzyme. Thus, it was shown that the structural modification of D-AB1 markedly lowers or abolishes the inhibitory activity toward GP, i. e. GP has a strict structure requirement for inhibitors at the catalytic site [35,36]. GP exists in two interconvertible forms: a dephosphorylated form (GP b) and a Ser14-phosphorylated form (GP a).…”

“…The inhibitory activity of five-membered sugar mimics toward GP has been investigated [35]. D-AB1 potently inhibited rabbit muscle GP b with an IC 50 value of 0.43 mM, whereas its enantiomer L-AB1 ( Fig.…”