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Spirophostins: Conformationally Restricted Analogues of Adenophostin A
Author(s) -
de Kort Martin,
Regenbogen Anouk D.,
Valentijn A. Rob P. M.,
Challiss R. A. John,
Iwata Yoriko,
Miyamoto Shuichi,
van der Marel Gijs A.,
van Boom Jacques H.
Publication year - 2000
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20000804)6:15<2696::aid-chem2696>3.0.co;2-y
Subject(s) - chemistry , inositol , stereochemistry , potency , biological activity , phosphorylation , receptor , combinatorial chemistry , biochemistry , in vitro
The synthesis, biological evaluation, and molecular modeling of two conformationally restricted analogues of adenophostin A ( 1 ), denominated as spirophostin (3 R )‐ 10 and (3 S )‐ 11 , as novel ligands for the D ‐ myo ‐inositol 1,4,5‐trisphosphate receptor (IP 3 R), is presented. These diastereoisomeric spiroketals are synthesized by spiroketalization of D ‐glucose derivatives (2 S )‐ 15 and (2 R )‐ 16 , separation of the protected isomers (3 R )‐ 19 and (3 S )‐ 20 , followed by phosphorylation and deprotection. The spirophostins (3 R )‐ 10 and (3 S )‐ 11 display comparable biological activity, with a 3 H‐IP 3 ‐displacing and Ca 2+ ‐releasing potency less than IP 3 and adenophostin A.