Oligonucleosides with a nucleobase-including backbone part 4 - A convergent synthesis of ethynediyl-linked adenosine tetramers

Deprotection of the tetramer 24, obtained by coupling the iodinated dimer 1 8 with the alkyne 23 gave the 8',5-ethynediyl-linked adenosine-derived tetr amer 27 (Scheme 3). As direct iodination of C(5')-ethynylated adenosine der ivatives failed, we prepared 18 via the 8-amino derivative 17 that was avai lable by coupling the imine 15 with the iodide 7; 15, in its turn, was obta ined from the 8-chloro derivative 12 via the 4-methoxybenzylamine 14 (Schem e 2). This method for the introduction of the S-iodo substituent was worked out with the N-benzoyladenosine 1 that was transformed into the azide 2 by lithiation and treatment with tosyl azide (Scheme I). Reduction of 2 led t o the amine 3 that was transformed into 7 I,3-Dipolar cycloaddition of 3 an d (trimethylsilyl)acetylene gave 6. The 8-substituted derivatives 4a-d were prepared similarly to 2, but could not be transformed into 7 The known chl oride 8 was transformed into the iodide 11 via the amines 9 and 10. The ami nes 3, 10, and 16 form more or less completely persistent intramolecular C( 8)N-H . . . O(5') H-bonds, while the dimeric amine 17 forms a ca. 50% persi stent H-bond. There is no UV evidence for a base-base interaction in the pr otected and deprotected dimers and tetramers.