Synthesis of 4-C-Alkyl Inositol 1,4,5-Trisphosphates and 1,3,4,5-Tetrakisphosphates

The preparation of 2,3,6-O-tribenzyl- and 2,6-O-dibenzyl-myo-inositols with β-primary, secondary, and tertiary 4-C-alkyl or aryl groups is reported. Five of these novel polyols are elaborated to 4-C-alkyl Ins(1,4,5)P3 and Ins(1,3,4,5)P4 analogues. Regio- and stereoselective introduction of 4-C-alkyl or aryl substituents proceeded via a 4-exo-methylene oxide. Subsequent regioselective reduction of an orthobenzoate provided a divergent method to access both InsP3 and InsP4 precursors. Previously unreported phosphorylation of the tertiary hydroxyl and global deprotection afforded novel analogues that retain their full complement of polar and charged binding features.