Oligonucleotide Analogues with Integrated Bases and Backbone. Part 28

The protected hydrazide‐linked uracil‐ and adenine‐derived tetranucleoside analogues 17, 19 , and 21 were synthesized in solution by coupling the dimeric hydrazines 6 and 10 with the carboxylic acids 7, 11 , and 16 . These hydrazines and acids were obtained by partially deprotecting the hydrazines 5, 9 , and 15 , and these were prepared by coupling the hydrazines 3 and 14 with the carboxylic acids 4 and 8 . The crystal structure analysis of the fully protected UU dimer 5 showed the formation of an antiparallel cyclic duplex with the uracil units H‐bonded via H? N(3) and O?C(2). Stacking interactions were observed between the uracil units with a buckle twist of 30.9°, and between the uracil unit II and the fluoren‐9‐yl group of Fmoc (=9H‐fluoren‐9‐yl)methoxycarbonyl). The hydrazide H? N(3′) and the C?O group of Fmoc form an intramolecular H‐bond. The uracil‐ and adenine‐derived, water‐soluble hydrazide‐linked self‐complementary octamers 23 – 32 and the non‐self‐complementary uracil derived decamer 33 were obtained by coupling the carboxylic acids 4 and 8 on a solid support. ¹H‐NMR Analysis in CDCl₃, mixtures of CDCl₃ and (D₆)DMSO, and (D₈)THF showed that the partially deprotected dimers 5, 6, 12 , and 13 form weakly associated linear duplexes. The partially deprotected tetramers 17 and 18 do not associate. The hydrazide‐linked octamers 23 – 32 do not stack in aqueous solution, and the non‐self‐complementary decamer 33 does not stack with the complementary strands of DNA 43 and RNA 42 . The Cbz‐protected amide‐linked octamers 51 – 56 derived from uracil, adenine, cytosine, and guanine were obtained as the main products by solid‐phase synthesis from the carboxylic acids 46 – 49 . The fully deprotected amide‐linked octamers proved insoluble, and could neither be purified nor analysed.