Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

The intramolecular aldol condensation of aldohexos-5-ulose derivatives of the D- and L- stereoseries has been studied. Only one of the four possible inososes was isolated from both stereoseries in reasonable yields (30-38%). The results obtained, together with the previous findings for the L- and L- stereoseries, allowed for the rationalisation of a mechanism of the reaction based on open-transition-state models and electron-withdrawing inductive effects. Complementary reductions of the intermediate inososes were possible by changing the reaction conditions, and two isomeric inositol derivatives were obtained with complete stereoselection from each inosose. The presented approach permits us to control the configuration of three out of the six stereocentres of the inositol frame and gives access to seven of the nine inositols. Noteworthy, for the D- derivative, the two-step sequence (condensation followed by reduction with NaBH(OAc) ) represents the biomimetic synthesis of -inositol. Furthermore, the sugar-based pathway leads directly to enantiomerically pure selectively protected inositols and does not require any desymmetrisation procedure which is needed when -inositol and other achiral precursors are employed as starting materials. As an example of application of the method, the indirect selective protection of secondary inositols' hydroxy functions, by placing specific protecting groups on the aldohexos-5-ulose precursor has been presented.