1-Adamantyl phosphonic

High reactivity is shown towards hydrogenphosphonates by highly strained hydrocarbon molecules. Thus, 1,3-dedihydroadamantane (133) reacts to give esters of 1-adamantyl-phosphonic acid under non-homolytic conditions , and tricyclo[4.1.0.0 ]heptane similarly affords the phosphonic esters 134 . 

This realization has not escaped the bioorganic community, and a number of research groups, notably those of Andrews and Berchtold, have synthesized molecules that are designed to mimic the presumed bicyclic transition state. A truly potent inhibitor has eluded our grasp, however, as reflected by the fact that most compounds investigated bind more weakly to chorismate mutase/prephenate dehydrogenase than does chorismate (as reflected by the substrate Km value). 1-Adamantyl phosphonic acid is the most potent inhibitor previously reported, with an I50 value twenty-fold less than chorismate Km under comparable conditions. 

In view of the varying behavior of chorismate mutases under different conditions and from different sources, we evaluated the best previously reported chorismate mutase inhibitor, 1-adamantyl phosphonate 35, in direct comparison with 41. Although the phosphonate... 

An adamantyl phosphonate, prepared from adamantyl bromide and Ag20, is easily cleaved with TFA in CH2Cl2. ... 

Diethyl pyrocarbonate has been used to convert uridine 2 - or 3 -phosphate into the 2, 3 -cyclic phosphate in high yield, and an adamantyl 2, 3 -cyclic phosphonate (421) was obtained when uridine reacted with I-adamantylphos-phonyl chloride. Phosphorylation of ribonucleosides with pyrophosphoryl chloride followed by hydrolysis in neutral solution afforded a simple synthesis of ribonucleoside 2, 3 -cyclic phosphate 5 -phosphates. Two phosphorylating agents mentioned earlier in this section can also yield 3, 5 -cyclic phosphates either by treatment of nucleoside 5 -(2-iV7V-dimethylamino-4-nitrophenyl phosphates) with acetic acid in pyridine (Scheme I4i) i, 83 qj. treatment of nucleoside 5 -(5 -methyl phosphorothioates) with iodine in pyridine. Another route to 3, 5 -cyclic phosphates involved cyclization of the nucleoside 5 -trichIoro-methylphosphonates (422) (obtained by the action of trichloromethylphosphonyl... 

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