Synthesis of 1L-chiro-inositol 2,3,5-trisphosphorothioate, the first partial agonist at the platelet myo-inositol 1,4,5-trisphosphate receptor.
The synthesis of L-chiro-inositol 2,3,5-trisphosphorothioate, a novel analogue of the second messenger D-myo-inositol 1,4,5-trisphosphate has been accomplished from the natural product L-quebrachitol. Phosphitylation of (-)-1L-1,4,6-tri-O-benzoyl-chiro-inositol obtained from L-quebrachitol followed by sulfoxidation of the products gave (-)-1L-1,4,6-tri-O-benzoyl-chiro-inositol 2,3,5-tris[di(2-cyanoethyl) phosphorothioate], which was deblocked using sodium in liquid ammonia to give 1L-(-)-chiro-inositol 2,3,5-trisphosphorothioate. 1L-chiro-Inositol 2,3,5-trisphosphorothioate is a partial agonist in the release of intracellular Ca2+ from saponin-permeabilised platelets and is both a key tool for pharmacological dissection of the polyphosphoinositide pathway of cellular signalling and a lead compound for the design of small molecule Ins(1,4,5)P3 receptor antagonists.
Liu
C
C
School of Pharmacy & Pharmacology, University of Bath, U.K.
al-Hafidh
J
J
Westwick
J
J
Potter
B V
BV
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009946:Organothiophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry*; D015290:Second Messenger Systems; D013237:Stereoisomerism
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009946:Organothiophosphorus Compounds; D018160:Receptors, Cytoplasmic and Nuclear; C089685:inositol 2,3,5-trisphosphorothioate; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium