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 adenosine derivatives 5 , 6 , 11 , and 12 ( Scheme 4 ). Similarly, the 5′‐epimeric dimer 16 was prepared by coupling 3 with the alkyne 8 ( Scheme 5 ). The propargylic alcohol 4 was transformed into the N ‐benzoylated alkyne 5 and into the amine 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 iodoadenosine 13 with the alkyne 5 to 14a was optimised; it is influenced by the N ‐benzoyl and the Et 3 SiO group of the alkyne, but hardly by the N ‐benzoyl group of the 8‐iodoadenosine. The alkyne is most reactive when it is O ‐silylated, but not N ‐benzoylated. Cross‐coupling of the 5′‐deoxyalkynes proceeded more slowly. The dimers 14a  –  d , 15b  –  d , and 16 were obtained in good yields ( Table 2 ). Deprotection of 14d and 16 led to 18 and 20 , respectively ( Scheme 5 ). The diols 17 and 19 and the hexols 18 and 20 prefer the syn ‐conformation in (D 6 )DMSO, completely for unit II and ≥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 ).