A new approach to the synthesis of the 5'-deoxy-5'-methylphosphonate linked thymidine oligonucleotide analogues.
A new synthetic method for the preparation of the 5'-deoxy-5'-methylphosphonate linked thymidine oligonucleotides (5'-methylenephosphonate analogues) was developed. The method is based on the use of a phosphonate protecting group, 4-methoxy-1-oxido-2-picolyl, enabling intramolecular nucleophilic catalysis which together with the condensing agent, 2,4,6-triisopropylbenzenesulfonyl chloride, secures fast and efficient formation of the 5'-methylenephosphonate internucleosidic bonds. The produced protected oligomers were treated with thiophenol and triethylamine to remove the phosphonate protecting groups, cleaved from the solid support using concentrated aqueous ammonia, and purified by HPLC. Several thymidine oligonucleotide analogues with the chain length of up to 20 nucleotidic units, in which all internal 5'-oxygen atoms have been replaced by methylene groups directly bound to phosphorus, were synthesised using this methodology.
Szabó
T
T
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, Sweden.
Kers
A
A
Stawinski
J
J
D004247:DNA / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010847:Picolines / Q000737:chemistry; D011071:Poly T / Q000138:chemical synthesis*; D013450:Sulfones; D013936:Thymidine / Q000031:analogs & derivatives*
D009943:Organophosphorus Compounds; D010847:Picolines; D013450:Sulfones; D011071:Poly T; C032627:methylphosphonic acid; C016801:2,4,6-triisopropylbenzenesulfonyl chloride; D004247:DNA; D013936:Thymidine