179015-84-0Relevant academic research and scientific papers
Synthesis of novel 3′-C-methylene thymidine and 5-methyluridine/cytidine H-phosphonates and phosphonamidites for new backbone modification of oligonucleotides
An,Wang,Maier,Manoharan,Ross,Cook
, p. 2789 - 2801 (2007/10/03)
Novel 5′-O-DMT- and MMT-protected 3′-C-methylene-modified thymidine, 5-methyluridine, and 5-methylcytidine H-phosphonates 1-7 with O-methyl, fluoro, hydrogen, and O-(2-methoxyethyl) substituents at the 2′-position have been synthesized by a new effective strategy from the corresponding key intermediates 3′-C-iodomethyl nucleosides and intermediate BTSP, prepared in situ through the Arbuzov reaction. The modified reaction conditions for the Arbuzov reaction prevented the loss of DMT- and MMT-protecting groups, and directly provided the desired 5′-O-DMT- and/or MMT-protected 3′-C-methylene-modified H-phosphonates 1-6 although some of them were also prepared through the manipulation of protecting groups after the P-C bond formation. The modified Arbuzov reaction of 3′-C-iodomethyl-5-methylcytidine 53, prepared from its 5-methyluridine derivative 42, with BTSP provided the 5-methylcytidine H-phosphonate 54, which was further transferred to the corresponding 4-N-(N- methylpyrrolidin-2-ylidene)-protected H-phosphonate monomer 7. 5′-O-MMT-protected 3′-C-methylene-modified H-phosphonates 5, 3, and 7 were converted to the corresponding cyanoethyl H-phosphonates 50, 51, and 56 using DCC as a coupling reagent. One-pot three-step reactions of 50, 51, and 56 provided the desired 3′-C-methylene-modified phosphonamidite monomers 8-10. Some of these new 3′-methylene-modified monomers 1-10 have been successfully utilized for the synthesis of 3′-methylene-modified oligonucleotides, which have shown superior antisense properties including nuclease resistance and binding affinity to the target RNA.
Synthesis and hybridisation properties of phosphonamidate ester modified nucleic acid
Fairhurst,Collingwood,Lambert,Taylor
, p. 467 - 472 (2007/10/03)
The replacement of the two backbone oxygen atoms of the phosphodiester linkage of DNA with carbon and nitrogen in the form of a phosphonamidate ester linkage, in both possible regioisomeric forms, is described. An alkylation reaction with the 3′-C-P-N-5′ methyl phosphonamidate regioisomer yielded the corresponding N-methylated analogues. For each example separation into individual phosphonamidate ester diastereoisomers was performed prior to incorporation into oligonucleotides. The effect upon duplex stability for DNA oligonucleotides containing each of these modifications with complimentary RNA is reported.
Heteroatomic oligonucleoside linkages
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, (2008/06/13)
PCT No. PCT/US94/03536 Sec. 371 Date Sep. 18, 1995 Sec. 102(e) Date Sep. 18, 1995 PCT Filed Mar. 30, 1994 PCT Pub. No. WO94/22886 PCT Pub. Date Oct. 13, 1994Oligonucleotide-mimicking macromolecules that have improved nuclease resistance are provided. Repl
The synthesis of novel modified nucleic acid monomers and their subsequent solid phase oligomerisation to give 3'-methylene phosphonate DNA (3MP)
Collingwood, Stephen P.,Douglas, Mark E.,Natt, Francois,Pieles, Uwe
, p. 645 - 648 (2007/10/03)
A protected hypophosphorus acid synthon allowed selective monoalkylation of hypophosphorus acid with 3'-iodo-methylene thymidine. The resulting H-phosphonous acid was an effective monomer for the solid phase synthesis of 3MP DNA which displayed strong binding to complementary RNA.
