Stereospecific Grignard-Activated Solid Phase Synthesis of DNA Methylphosphonate Dimers
- 1 January 1996
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 61 (2) , 510-513
- https://doi.org/10.1021/jo9517499
Abstract
Stereoregular Rp or Sp DNA methylphosphonate dimers have been synthesized on a solid phase support. A deprotected 5‘-hydroxyl-N2-isobutanoyldeoxyguanosine 3‘-O-succinate coupled to high-loaded polyethylene glycol (PEG) coated polystyrene beads (HLP) was activated with a Grignard reagent, t-BuMgCl. After activation was complete, a pure diastereoisomer of 5‘-(dimethoxytrityl) N-benzoyldeoxynucleoside 3‘-(p-nitrophenyl methylphosphonate) p-nitrophenyl ester (Rp or Sp) was added. Coupling of the activated 5‘-hydroxyl to the 3‘-methylphosphonate ensued, releasing nitrophenol, yielding the Rp or Sp dimer, respectively. The dimers were then cleaved from the solid support, deprotected, and purified, yielding methylphosphonate DNA dimers of defined stereochemistry.Keywords
This publication has 6 references indexed in Scilit:
- Stereospecific grignard activated coupling of a deoxynucleoside : Methylphosphonate on a polyethylene glycol supportTetrahedron Letters, 1994
- Synthesis of specific diastereomers of a DNA methylphosphonate heptamer, d(CpCpApApApCpA), and stability of base pairing with the normal DNA octamer d(TpGpTpTpTpGpGpC)Nucleic Acids Research, 1994
- Large scale, liquid phase synthesis of oligonucleotides by the phosphoramidite approachNucleic Acids Research, 1993
- Matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a powerful tool for the mass and sequence analysis of natural and modified oligonucleotidesNucleic Acids Research, 1993
- Strategies for administering targeted therapeutic oligodeoxynucleotidesTrends in Biotechnology, 1992
- Boron-containing nucleic acids. 2. Synthesis of oligodeoxynucleoside boranophosphatesJournal of the American Chemical Society, 1990