Synthesis of Adenophostin Analogues Lacking the Adenine Moiety as Novel Potent IP₃ Receptor Ligands:  Some Structural Requirements for the Significant Activity of Adenophostin A

Abstract

1- O- Tetrahydrofuranyl-α- d -glucopyranose derivatives 5 − 8 were designed and synthesized as novel IP 3 receptor ligands. The glycosidation reactions between fluoroglycosyl donor 23 and tetrahydrofuran derivatives 11 − 14 as glycosyl acceptors selectively gave the corresponding α-glycosides, which were converted into the target compounds 5 − 8 via the introduction of phosphate groups using the phosphoramidite method. Among these compounds, 1- O- tetrahydrofuranyl-α- d -glucopyranose trisphosphate derivatives 5 and 8 significantly inhibited the binding of [ 3 H] IP 3 to IP 3 receptor from porcine cerebella, with IC 50 values of 25 and 27 nM, respectively, which were comparable to the affinity of IP 3 itself.