A study on the allylic substitution of (1R,5R,8R)- and (1R,5R,8S)-8-hydroxy-2-oxabicyclo[3.3.0]oct-6-en-3-one derivatives - Preparation of (1S,2R,3R)-9-[2-hydroxy-3-(2-hydroxyethyl)cyclopent-4-en-1-yl]-9H-adenine

The palladium-catalyzed substitution of acylated (1R,5R,8R)- and (1R,SR,8S) -8-hydroxy-2-oxabicyclo[3.3.0] ones has been studied using a number of C- a nd N-nucleophiles, In all cases, the exo derivatives (8R) were found to be more reactive than the corresponding endo derivatives (8S). The reaction wa s found to give good yields and a single product when sodium dimethyl malon ate was used as the nucleophile. However, when less reactive C- and N-nucle ophiles were employed, the reaction gave inseparable mixtures of both C-6 a nd C-8 substituted products, thus Limiting the synthetic use of the reactio n with these nucleophiles. Additionally, Mitsunobu substitution of (1R,5R,8 R)-8-hydroxy-2-oxabicyclo[3.3.0]oct-B-en-3-one (3) with 6-chloropurine, fol lowed by reduction of the lactone moiety and treatment with Liquid ammonia, gave the carbocyclic nucleoside (1S,2R,3R)-9-[2-hydroxy-3-(2-hydroxyethyl) cyclopent-4-en-1-yl]-9H-adenine (19), which can be viewed as an analogue of the carbocyclic nucleoside BCA.