A Highly Efficient One-Flask Method for the Preparation of the Individual Diastereoisomers of Ribonucleoside 3', 5'-Cyclic N-Substituted Phosphoramidates via the Direct Appel Reaction. X-ray Structure of trans-5-Isopropyl-2'-deoxyuridine 3', 5'-Cyclic N-Benzylphosphoramidate

Laszlo Parkanji, Jozsef Beres, Wesley G. Bentrude, Alajos KáLmáN, Alan E. Sopchik

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Abstract

A superior method for the preparation of 3', 5'-cyclic N-substituted phosphoramidates of purine and pyrimidine ribo and deoxyribonucleosides is reported. An Appel-type reaction of various 3', 5'-cyclic nucleoside monophosphates using a Ph3P/CCl4pretreatment followed by addition of the requisite amine gives the corresponding phosphoramidate as a mixture of diastereomers in 31-85% isolated yields. Separation of the individual diastereomers is accomplished by chromatography on Si02. Most notably the reactions proceed readily with 3', 5'-cyclic ribonucleoside monophosphates without protection of the 2'-OH or potentially reactive functionality on the nitrogen base. In most instances both diastereomers are formed in useful amounts. Amino groups used included C6-H5CH2NH, C6H6NH, and (CH2)5N. Nucleosides employed were adenosine, deoxyadenosine, uridine, 5-iso-propyl-2'-deoxyuridine, and 5-iodo-2'-deoxyuridine, An X-ray crystallographic study of one diastereomer of the N-benzylphosphoramidate based on the 3'5'-cyclic diester of adenosine established the trans relationship of the PhCH2NH and nitrogen base as well as the equatorial position of the PhCH2NH on the chair form of the 1,3,2-dioxaphosphorinane ring. The structural parameters observed for the five and six-membered rings are consistent with those of other neutral cyclic nucleotide derivatives.

Original languageEnglish
Pages (from-to)1271-1278
Number of pages8
JournalJournal of Organic Chemistry
Volume50
Issue number8
DOIs
Publication statusPublished - Apr 1985

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ASJC Scopus subject areas

  • Organic Chemistry

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