Phenyl phosphorodichloridate in the synthesis of cyclic phosphate diesters of biological interest

Abstract

The general usefulness of phenyl phosphorodichloridate (PPDC) in the synthesis of non-nucleoside cyclic phosphates is described. The method is illustrated with several examples including cyclic phosphates incorporating 6-9 members. However, the reagent could not be used for the preparation of 5-membered cyclic phosphates or 3'', 5''-cyclic AMP from adenosine. A number of observations showed that PPDC cannot be used for the synthesis of strained or reactive cyclic phosphates. A convenient synthesis of cis- and trans-2-hydroxycyclopentanemethanol and a simple, quantitative method of separation of the 2 isomers is described. A number of cyclic phosphates were tested as substrates and inhibitors for cyclic purine phosphodiesterase and protein kinase.