Oligomers that adopt predictable conformations ("foldamers") are subjects of increasing interest from the perspectives of both fundamental research and applications.[1] The study of unnatural oligomers that display secondary structures analogous to those of proteins or nucleic acids provides new insight on the parameters that influence the "foldability" of a backbone, e.g., the relationships between conformational stability and number of residues or residue flexibility. As the rules that govern shape are elucidated for new backbones, this
Suzuki-Miyaura cross-coupling of haloaromatic compounds with arylboronic acids provides a simple entry to biaryl systems. Despite its ease, to date, there are no detailed investigations of this procedure for deoxynucleoside modification. As shown in this study, a wide variety of C-6 arylpurine 2'-deoxyriboside (C-6 aryl 2'-deoxynebularine analogues) and C-2 aryl 2'-deoxyinosine analogues can be conveniently prepared via the Pd-mediated cross-coupling of arylboronic acids with the C-6 halonucleosides, 6-bromo- or 6-chloro-9[2-deoxy-3,5-bis-O-(tert-butyldimethylsilyl)-beta-D-erythro-pentofuranosyl]purine (1 and 2), and the C-2 halonucleoside, 2-bromo-O(6)-benzyl-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyinosine (3). Although bromonucleoside 1 proved to be a good substrate for the Pd-catalyzed Suzuki-Miyaura cross-couplings, we have noted that for several C-6 arylations, the chloronucleoside 2 provides superior coupling yields. Also described in this study is a detailed evaluation of catalytic systems that led to optimal product recoveries. Finally, a comparison of the C-C and C-N bond-forming reactions of deoxynucleosides is also reported. On the basis of this comparison, we provide evidence that C-N bond formation at the C-6 position, leading to N-aryl 2'-deoxyadenosine analogues, is more sensitive to the ligand used, whereas C-C bond-forming reactions at the same position are not. In contrast to the ligand dependency exhibited in C-N bond formation at the C-6 position, comparable reactions at the C-2 position of purine deoxynucleosides proceed with less sensitivity to the ligand used.
The 3',5'-bis-O-TBDMS derivative of 2'-deoxyguanosine can be converted to its O6-alkyl and O6-aryl ethers as well as to N6-substituted diaminopurine nucleosides in two simple steps. Also described is a novel, nonaqueous, one-step O6-desulfonylation method that leads to deprotection of the carbonyl moiety of 2'-deoxyguanosine.
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