Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates

US5177198A · kind A · utility

Assignees

• The University of N.C. at Chapel Hill · US
• Duke University · US
• Boron Biologicals, Inc. · US

Inventors

• Bernard F. Spielvogel · Cary, US
• Anup Sood · Flemington, US
• Iris H. Hall · Chapel Hill, US
• Barbara Ramsay Shaw · Durham, US

Key dates

• Filing date: Nov 30, 1989
• Grant date: Jan 5, 1993
• Expiry date: Nov 30, 2009

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A process of making oligoribonucleoside and deoxyribonucleoside boranophosphates and salts thereof is disclosed. The process comprises the steps of condensing a ribonucleotide or deoxyribonucleotide with a nucleoside phosphitylating agent, wherein the phosphitylating agent includes a 5' -OH group protected by an acid-labile protecting group and a moiety bonded to the phosphorus atom therein that is a stronger proton acceptor than the 5'-OH group of the ribonucleotide or deoxyribonucleotide to form a reaction intermediate, then oxidizing the reaction intermediate so formed with a compound comprising a Lewis base and a boron-containing substituent, wherein the Lewis base is a weaker electron donor than the phosphite phosphorus of the reaction intermediate, to form a ribonucleotide or deoxyribonucleotide boranophosphate. These steps are repeated on the nucleotide boranophosphate to form an oligonucleotide boranophosphate.