SYNTHESIS OF ANALOGS OF OLIGONUCLEOTIDES - SYNTHESIS OF UNPROTECTED C-LINKED DI-NUCLEOTIDES AND TRI-NUCLEOTIDES

The Wittig reaction between the N-benzyloxymethylthymidine-derived yli de 25 and the aldehyde 16 followed by hydrogenolysis gives access to t he unprotected C-linked dinucleotide 20 on a multi-gram scale. Oxidati on of the dinucleotide gives the aldehyde 27 which is condensed with t he ylide 25 to give the unprotected bis-C-linked trinucleotide 29 afte r hydrogenolysis, The mono-C-linked trinucleotide 44 is prepared by ox idation of the dinucleotide ester 34 to the aldehyde 36 which is conde nsed with the ylide 25 followed by hydrogenolysis to give the mono-C-l inked trinucleotide ester 38. This intermediate is also prepared from the C-linked dinucleotide 20 by conversion into the phosphoramidite 41 which is coupled with 3-acetylthymidine 15 to give the mono-C-linked trinucleotide phosphite 42. Oxidation and deprotection give the phosph ate triester 38. Treatment of 38 with methanolic ammonia gives the ful ly unprotected mono-C-linked trinucleotide 44.