Synthesis of fluorodeoxy analogues of myo-inositol.

Accumulating evidence strongly suggests that the action of a phospholipase C on phosphoinositides in the cell membrane in response to the activation of a receptor is an integral part of an intracellular signalling pathway. Specific inhibitors of this enzyme and the site-specific kinases involved in inositide metabolism are urgently required to establish their function. An approach to the design of such inhibitors would be to replace single hydroxyl groups on myo-inositol by a fluorine atom. Such analogues would probably be incorporated into the cell by the same pathway as myo-inositol but subsequent phosphorylation at the substituted position would be blocked. Other syntheses have been published for such analogues [ 1, 21. This communication reports high-yield routes to these compounds from myo-inositol and their separation as optical isomers. The synthetic route to the meso-compound, 5-deoxy-5fluoro-myo-inositol, is outlined in Scheme 1. The 5-position of compound 1, available in good yield by the method of Garegg &L Lindberg [3] , was inverted to give the neo-inositol derivative by nucleophilic displacement of a toluenesulphonate group so that fluorination with diethylamino-