@article{e197348a285e4ba68afd8216b465d813,
title = "Use of phosphorus oxychloride in synthesizing nucleotides and ollgonucleotides",
abstract = "Procedures are described for phosphorylating protected nucleotides, oligonucleotides and phosphoramidate oligonucleotide derivatives at the 3′-hydroxyl group. The conditions (phosphorylation with phosphorus oxychloride and pyridine in dioxane followed by hydrolysis with aqueous pyridine) are sufficiently mild that base labile (trifluoroacetylamino; β-cyanoethyl phosphotriester) and acid labile (O-monomethoxytrityl; phosphoramidate) functions are retained intact. Application of the technique is illustrated by the synthesis of dpT, dTp, d(CF3CONH)Tp, dTpNTp, and dTpNTpNTp. In addition, the utilization of phosphorus oxychloride in joining thymidine derivatives and dinucleoside phosphotriester blocks via phosphodiester links is described.",
author = "Mungall, {W. S.} and Greene, {G. L.} and Miller, {P. S.} and Letsinger, {R. L.}",
note = "Funding Information: The resulting gum was treated with anhydrous 3 '-O-mono-p-methoxytrityl-llc ~ thymidine (103 mg, 0. 20 mmol) and 0. 024 ml of pyridine in 2. 5 ml of dioxane. The mixture was stirred for 5 hours, treated with 0. 5 ml of aqueous pyridine and concentrated to a syrup. The protecting groups were removed by treatment with 2 ml of 80^ acetic acid at 100° for 10 minutes. The acetic acid was evaporated and the residue was mixed with 10 ml of water. After extraction with two 3 ml portions of ether, the aqueous phase was diluted to 25 ml with water. A 1 ml aliquot of this solution chromatographed on paper in solvent F revealed three components: Rf 0. 54 (2. 09 A260 units), Rf 0. 66 (57. 8A26Ounits; dTpT) and Rf 0.76 (3. 04 A230 units, dT). The dTpT represents a 18% yield based on 5 '-O-tritylthymidine. It was completely degraded by both snake venom and spleen phosphodiesterase (nucleoside:nucleotide = 0. 93:1. 00 from reaction of the venom enzyme and 0. 95:1. 00 from reaction of the spleen enzyme). ACKNOWLEDGEMENT This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health (Grant GM10265). REFERENCES",
year = "1974",
month = apr,
doi = "10.1093/nar/1.4.615",
language = "English (US)",
volume = "1",
pages = "615--627",
journal = "Nucleic acids research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "4",
}