Expedient Chemical Synthesis of Sequence-Specific 2',5'-Oligonucleotides

Article abstract of DOI:10.1021/jo00209a014

A rapid chemical approach to the preparation of sequence-specific 2',5'-oligonucleotides and analogues of 2-5A is described.For instance, reaction of the 5'-phosphoromorpholidate of adenosine (MopA, 14) with the 5'-phosphoroimidazolidate of inosine (ImpI, 17), under conditions of lead ion catalysis, gave MopA2'p5'I (19a) in 21percent yield.Acid hydrolysis of 19a gave pA2'p5'I, which then was converted to the corresponding 5'-phosphoroimidazolidate Imp5'A2'p5'I (19c) through redox condensation with triphenylphosphine, imidazole, and 2,2-dipyridyl disulfide.Lead ion catalyzed condensation of 19c with Mop5'A (14) gave Mop5'A2'p5'A2'p5'I (30) in 17percent yield.By acid hydrolysis, 30 could be converted to the corresponding 5'-monophosphate, or, by reaction with pyrophosphate in DMF, to the corresponding 2-5A analogue, ppp5'A2'p5'A2'p5'I (5b).The following oligonucleotides were prepared by using similar methodology: ppp5'A2'p5'A2'p5'A (1b), ppp5'A2'p5'I2'p5'A (4b), ppp5'I2'p5'A2'p5'A (3b), and ppp5'A2'p5'A2'p5'(2'dA) (2b).