Research Project
3498423
The overall objective of this study is to develop a simple, general, and practical method for resolving derivatives of DL-myo-inositol into D- and L- enantiomers. A novel approach based on putative enantioselective hydrolysis catalyzed by hydrolase enzymes is suggested. The pure enantiomers are required as key synthons for the preparation of D- myo inositol-1,4,5-trisphosphate, the myo-inositol-1-phosphono-6-glycans, and , other compounds related to these intracellular second messenger molecules, and for the synthesis of analogues as potential therapeutic agents. The Phase I program is designed to establish the feasibility of the general approach. For this, the hydrolysis of selected DL-myo-inositol esters as model substrates, catalyzed by a number of hydrolase enzymes will be studied to determine relationships between structural features and esterase activity, with emphasis on synthons for the preparation of D-myo-inositol- 1-phosphate, D-myo-inositol-1,4,5-trisphosphate, and their L-enantiomers. During Phase II, the general approach will be extended and applied for the preparation of other members of the phosphoinositol series derived from the phosphatidylinositol metabolic cycle, and to the design, synthesis and evaluation of their structural and biochemical analogues.
