Concepedia

Publication | Closed Access

Spirophostins: Conformationally Restricted Analogues of Adenophostin A

DOI

16

Citations

0

References

2000

Year

Martin de Kort, Anouk D. Regenbogen, A. Rob P.M. Valentijn, R. A. John Challiss, Yoriko Iwata, Shuichi Miyamoto, Gijs A. van der Marel, Jacques H. van Boom
Chemistry - A European Journal

Abstract

The synthesis, biological evaluation, and molecular modeling of two conformationally restricted analogues of adenophostinA (1), denominated as spirophostin (3R)-10 and (3S)-11, as novel ligands for the D-myo-inositol 1,4,5-trisphosphate receptor (IP3R), is presented. These diastereoisomeric spiroketals are synthesized by spiroketalization of D-glucose derivatives (2S)-15 and (2R)-16, separation of the protected isomers (3R)-19 and (3S)-20, followed by phosphorylation and deprotection. The spirophostins (3R)-10 and (3S)-11 display comparable biological activity, with a 3H-IP3-displacing and Ca2+-releasing potency less than IP3 and adenophostin A.