Enhanced brain delivery of an anti-HIV nucleoside 2'-F-ara-ddI by xanthine oxidase mediated biotransformation.

In order to enhance the brain delivery of 2'-F-ara-ddI, 2'-F-ara-ddP 6 was synthesized and its in vitro and in vivo bioconversion reaction studied. For the study, a new efficient synthetic method for 2'-F-ara-ddP 6 was developed from 5-benzoyl-1,2-O-isopropylidene-3-deoryribose 1. For in vitro study 2'-F-ara-ddP was incubated in pH 2, mouse liver homogenate, and mouse serum at 37 o C. No degradation was observed in pH 2 and serum, while in liver homogenate 2'-F-ara-ddP was almost completely converted to 2'-F-ara-ddI within 20 min (t 1/2 =3.54 min)