title: Spirophostins: conformationally restricted analogues of adenophostin A.
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.
authors.affiliation: Leiden Institute of Chemistry, Gorlaeus Laboratories Leiden University, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: de Kort
authors.forename: A D
authors.initials: AD
authors.lastname: Regenbogen
authors.forename: A R
authors.initials: AR
authors.lastname: Valentijn
authors.forename: R A
authors.initials: RA
authors.lastname: Challiss
authors.forename: Y
authors.initials: Y
authors.lastname: Iwata
authors.forename: S
authors.initials: S
authors.lastname: Miyamoto
authors.forename: G A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: J H
authors.initials: JH
authors.lastname: van Boom
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D002118:Calcium; D002120:Calcium Channel Agonists / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D002120:Calcium Channel Agonists; C085029:adenophostin A; D000241:Adenosine; D002118:Calcium