352286-01-2Relevant academic research and scientific papers
Xylopyranoside-based agonists of D-myo-inositol 1,4,5-trisphosphate receptors: Synthesis and effect of stereochemistry on biological activity
Rosenberg, Heidi J.,Riley, Andrew M.,Marwood, Rachel D.,Correa, Vanessa,Taylor, Colin W.,Potter, Barry V.L.
, p. 53 - 66 (2007/10/03)
The synthesis of a series of tetrahydrofuranyl α- and β-xylopyranoside trisphosphates, designed by excision of three motifs of adenophostin A is reported. The synthetic route features improved preparations of allyl α-D-xylopyranoside and its 2-O-benzyl ether, and gives access to four diastereoisomeric trisphosphates, which show a range of abilities to mobilise Ca2+ from the intracellular stores of hepatocytes. A comparison of the potencies of the four trisphosphates provides useful information relating to the effects of stereochemical variation on the recognition of carbohydrate-based trisphosphates by D-myo-inositol 1,4,5-trisphosphate receptors. 1-O-[(3′S,4′R)-3-hydroxytetrahydrofuran-4-yl] α-D-xylopyranoside 3,4,3′-trisphosphate (8) is the most active member of the series with a potency close to Ins(1,4,5)P3; a β-linked analogue, 1-O-[(3′R,4′S)-3-hydroxytetrahydrofuran-4-yl] β-D-xylopyranoside 3,4,3′-trisphosphate, is ca. 20-fold weaker than Ins(1,4,5)P3, and the other compounds are much less active. While no compound attained a potency close to that of adenophostin A, we believe that 8 represents the minimal structure for potent Ca2+-releasing activity in this type of carbohydrate-based analogue.
