jo050847j_si_001.pdf (1.02 MB)
Synthesis and Reactions of 2-Chloro- and 2-Tosyloxy-2‘-deoxyinosine Derivatives
journal contribution
posted on 2005-09-02, 00:00 authored by Narender Pottabathini, Suyeal Bae, Padmanava Pradhan, Hoh-Gyu Hahn, Heduck Mah, Mahesh K. LakshmanConvenient syntheses of 2-chloro- and 2-tosyloxy-2‘-deoxyinosine as their tert-butyldimethylsilyl
ethers are described. Both compounds can be synthesized via a common route and rely on
commercially available 2‘-deoxyguanosine. The present method leading to the chloro nucleoside is
operationally simpler compared to previously reported glycosylation techniques where isomeric
products were obtained. Both electrophilic nucleosides can be used for the preparation of
N-substituted 2‘-deoxyguanosine analogues via displacement of the leaving groups, and a comparison
of their reactivities shows the chloro analogue to be superior. Interestingly, a Pd catalyst-mediated,
two-step, one-pot conversion of an allyl-protected chloro nucleoside intermediate to the final modified
2‘-deoxyguanosine derivatives is also feasible. On the basis of these observations, initial assessments
of Pd-catalyzed aryl amination as well as a C−C cross-coupling have also been performed with the
chloro and tosyloxy nucleoside substrates. Results indicate a potentially high synthetic utility of
2-chloro-2‘-deoxyinosine and in many instances this derivative can supplant the bromo and fluoro
analogues that are more cumbersome to prepare or are not readily available.