Oligonucleosides with a nucleobase-including backbone Part 3 - Synthesis of acetyleno-linked adenosine dimers

The adenosine-derived dimers 14a-d and 15b-d have been prepared by coupling the protected 8-iodoadenosines 3 and 13 with the C(5')-ethynylated adenosi ne derivatives 5, 6, 11, and 12 (Scheme 4). Similarly, the 5'-epimeric dime r 16 was prepared by coupling 3 with the alkyne 8 (Scheme 5). The propargyl ic alcohol 4 was transformed into the N-benzoylated alkyne 5 and into the a mine 6, while the epimeric alcohol 7 was converted to the epimeric amine 8 and the 5'-deoxy analogues 11 and 12 (Scheme 3). Cross-coupling of the iodo adenosine 13 with the alkyne 5 to 14a was optimised;it is influenced by the N-benzoyl and the Et3SiO group of the alkyne, but hardly by the N-benzoyl group of the 8-iodoadenosine. The alkyne is most reactive when it is O-sily lated, but not N-benzoylated. Cross-coupling of the 5'-deoxyalkynes proceed ed more slowly. The dimers 14a-d, 15b-d, and 16 were obtained in good yield s (Table 2). Deprotection of 14d and 16 led to 18 and 20, respectively (Sch eme 5). The diols 17 and 19 and the hexols 18 and 20 prefer the syn-conform ation in (D-6)DMSO, completely for unit II and greater than or equal to 80% for unit I; they exhibit partially persistent intramolecular O(5')-H . . . N(3) H-bonds. The persistence increases from 18% (unit I of 19), 32% (unit II of 17 and 19), 45% (unit I of 17), 52% (unit II of 18 and 20), and 55% ( unit I of 20) to 82% (unit I of 18).