New approaches to the synthetic problems of myo-inositol phosphates and their biological utilities

Abstract

A number of myo-inositol phosphates (IPn) have been implicated as either second messengers or key metabolic intermediates in the intracellular signal transduction pathways. Syntheses of all possible 9 and 12 regioisomers of myo-inositol tetrakis- and tris-phosphates (IP4 and IP3), respectively were accomplished from myo-inositol via its di-and tri-benzoate derivatives as the key intermediates. The requisite sets of myo-inositol benzoate intermediates were most conveniently produced by base-catalyzed migration of the benzoate group in partially benzoylated inositols, followed by suitable separation methods. The biological properties of the synthetic IPn samples have been examined in terms of their abilities for the receptor binding, Ca2+ release and its interference, and for the possible inhibition of the metabolic enzymes such as kinases.