Synthesis of (±)-myo-inositol 1,4,5-trisphosphate and the novel analogue (±)-myo-inositol 1,4-bisphosphate 5-phosphorothioate

✍ Scribed by Nicholas J. Noble; Allan M. Cooke; Barry V.L. Potter

• Publisher: Elsevier Science
• Year: 1992
• Tongue: English
• Weight: 758 KB
• Volume: 234
• Category: Article
• ISSN: 0008-6215
• DOI: 10.1016/0008-6215(92)85047-4

✦ Synopsis

Novel routes to myo-inositol 1,4,5trisphosphate and a phosphorothioate analogue involving mixed P(V) and P(III) chemistry have been developed. Phosphorylation of 2,3,6-tri-O-benzyl-myo-inositol l-[di-(2,2,2-trichloroethyl) phosphate] with bis(2,2,2-trichloroethyl) phosphorochloridate gave a mixture of the 1,4-and l$bisphosphate derivatives from which the 1,4-bis[di-(2,2,2-trichloroethyl) phosphate] 9 crystallised. Phosphitylation of HO-5 in 9 followed by oxidation yielded the 1,4-bis[di-(2,2,2-trichloroethyl) phosphate] S-[di-(2-cyanoethyl) phosphate] which was deblocked using sodium in liquid ammonia to give (+ )-myo-inositol 1,4,5_trisphosphate. Phosphitylation of HO-S in 9 followed by sulphoxidation generated the 1,4-bis[di-(2,2,2-trichloroethyl) phosphate] 5-[di-(2cyanoethyl) thiophosphate] which was deblocked to give (+)-myo-inositol 1,4-bisphosphate 5-phosphorothioate. Removal of the 2,2,2-trichloroethyl group, using sodium in liquid ammonia, represents a new method for removing this protecting group.