Synthesis and reactions of 2-chloro- and 2-tosyloxy-2'-deoxyinosine derivatives.
Convenient 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.
Pottabathini
Narender
N
Department of Chemistry, City College and City University of New York, 138th Street at Convent Avenue, New York, New York 10031-9198, USA.
Bae
Suyeal
S
Pradhan
Padmanava
P
Hahn
Hoh-Gyu
HG
Mah
Heduck
H
Lakshman
Mahesh K
MK
D003849:Deoxyguanosine / Q000737:chemistry; D007288:Inosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D007288:Inosine; D003849:Deoxyguanosine; C012271:deoxyinosine