The "Other" Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances in myo-Inositol Chemistry)

Cell signaling via inositol phosphates, in particular via the second messenger myo‐inositol 1,4,5‐trisphosphate, and phosphoinositides comprises a huge field of biology. Of the nine 1,2,3,4,5,6‐cyclohexanehexol isomers, myo‐inositol is pre‐eminent, with “other” inositols (cis‐, epi‐, allo‐, muco‐, neo‐, l‐chiro‐, d‐chiro‐, and scyllo‐) and derivatives rarer or thought not to exist in nature. However, neo‐ and d‐chiro‐inositol hexakisphosphates were recently revealed in both terrestrial and aquatic ecosystems, thus highlighting the paucity of knowledge of the origins and potential biological functions of such stereoisomers, a prevalent group of environmental organic phosphates, and their parent inositols. Some “other” inositols are medically relevant, for example, scyllo‐inositol (neurodegenerative diseases) and d‐chiro‐inositol (diabetes). It is timely to consider exploration of the roles and applications of the “other” isomers and their derivatives, likely by exploiting techniques now well developed for the myo series. Turtle reconfiguration: “Agranoff's Turtle”, used to visualize myo‐inositol, with head, tail, and limbs rearranged yields another eight stereoisomers. These have different properties in biological systems, and some may have medical applications. All can be synthesized by a variety of routes, but are much less studied than myo‐inositol. The synthesis and roles of these isomers and their phosphates are discussed, with recent advances in myo‐inositol chemistry.