Spirophostins: Conformationally restricted analogues of adenophostin A

The synthesis, biological evaluation, and molecular modeling of two conform ationally restricted analogues of adenophostin A (1), denominated as spirop hostin (3R)-10 and (3S)-11, as novel ligands for the D-myo-inositol 1,4,5-t risphosphate receptor (IP3R), is presented, These diastereoisomeric Spiroke tals are synthesized by spiroketalization of D-glucose derivatives (2S)-15 and (2R)-16, separation of the protected isomers (3R)-19 and (3S)-20, follo wed by phosphorylation and deprotection, The spirophostins (3R)-10 and (3S) -11 display comparable biological activity, with a H-3-IP3-displacing and C a2+-releasing potency less than IP3 and adenophostin A.