Streamlined synthesis of phosphatidylinositol (PI), PI3P, PI3,5P2, and deoxygenated analogues as potential biological probes.
Highly direct total syntheses of phosphatidylinositol (PI), phosphatidylinositol-3-phosphate (PI3P), phosphatidylinositol-3,5-bisphosphate (PI3,5P2), and a range of deoxygenated versions are reported. Each synthesis is carried out to deliver the target in optically pure form. The key step for each synthesis is a catalytic asymmetric phosphorylation reaction that affects desymmetrization of an appropriate myo-inositol precursor. Elaboration to each target compound is then carried out employing a diversity-oriented strategy from the common precursors. In addition to three natural products, several additional streamlined total syntheses of deoxygenated PI analogues are reported. These syntheses set the stage for high-precision biological investigations of polar headgroup/biological target interactions of these membrane-associated signaling molecules.
Xu
Yingju
Y
Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Sculimbrene
Bianca R
BR
Miller
Scott J
SJ
D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D018129:Phosphatidylinositol Phosphates / Q000138:chemical synthesis* / Q000737:chemistry; D010716:Phosphatidylinositols / Q000138:chemical synthesis* / Q000737:chemistry; D010766:Phosphorylation; D013237:Stereoisomerism
D005456:Fluorescent Dyes; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C106336:phosphatidylinositol 3,5-diphosphate; C055525:phosphatidylinositol 3-phosphate