2-aminopurine derivatives with C6-substituted olefin as novel cross-linking agents and the synthesis of the corresponding beta-phosphoramidite precursors

The 6-vinylated 2-aminopurine nucleoside (1), which was prepared by the Pd(0)-catalyzed cross-coupling reaction using guanosine 6-O-tosylate and vinyl-tributylstannane, has been demonstrated as a potential cross-linking agent. However, attempts for its incorporation into oligonucleotides were unsuccessful because of the high reactivity toward nucleophiles. In this study, new 2'-deoxy nucleoside derivatives with 6-(2-substituted vinyl)-2-aminopurine were designed to diminish the reactivity of the vinyl group. These new nucleosides have been shown to maintain reactivity toward potent nucleophiles such as butylamine and thiols, suggesting that they would form cross-linking with the target nucleobase due to the proximity within the sense-antisense duplex. Thus, the corresponding beta-phosphoramidite precursors were successfully prepared, and were applied to an automated oligonucletotide synthesizer. (C) 1997 Elsevier Science Ltd.