| Popis: |
Phosphonate analogs of 5-phosphorylribose 1-α-diphosphate (PRPP), in which the anomeric oxygen has been replaced by carbon ( C -glycoside analogs), have been prepared in multistep syntheses. The exact “ribosyl” analog could not be elaborated from the 3,4-isopropylidene precursor, 9 , owing to attack of the 3-OH onto the phosphonyl phosphorus under conditions for removal of the blocking group. Nevertheless, this isopropylidene derivative is a competitive inhibitor ( K i K m (PRPP) = 16.4 ), with respect to PRPP, of yeast orotate phosphoribosyltransferase. This result indicates that the enzyme can accommodate a good deal of bulk at the corresponding 2- and 3-hydroxyl groups of PRPP. The “α-arabinosyl” analog, 15 , was successfully synthesized with ultimate stereospecificity that results from the preferential hydrolysis of the “β-anomer” in the same fashion as for the hydrolysis of 9 . This α-arabinosyl analog is also a competent competitive inhibitor of yeast orotate phosphoribosyltransferase ( K i K m (PRPP) = 54 ). Both compounds are considerably more stable than PRPP both chemically and biochemically. |
