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