Activators for oligonucleotide synthesis

US7501505B2 · kind B2 · utility

Assignee

• Avecia Biotechnology, Inc. · US

Inventors

• Nanda Sinha · Boxboro, US
• William Edward Zedalis · Fitchburg, US
• Gregory Keith Miranda · Princeton, US

Key dates

• Filing date: Jul 1, 2002
• Grant date: Mar 10, 2009
• Expiry date: Nov 17, 2023

Classification

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

Abstract

A process for the synthesis of oligonucleotides using phosphoramidite chemistry is provided. The process employs as activator a 1,1-dioxo-1,2-dihydro-1λ6-benzo[d]isothiazol-3-one, preferably in the presence of an organic base. The 1,1-dioxo-1,2-dihydro-1λ6-benzo[d]isothiazol-3-one is represented by the following structural formula:wherein p is 0 or an integer from 1 to 4; X7 is O or S; R for each occurrence is a substituent, preferably each independently, a halo, a substituted or unsubstituted aliphatic group, —NR11R12, —OR13, —OC(O)R13, —C(O)OR13, or cyano; or two adjacent R groups taken together with the carbon atoms to which they are attached form a six membered saturated or unsaturated ring; R11 and R12 are each, independently, —H, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group; and R13 is a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group. Preferred organic bases are pyridine, 3-methylpyridine, or N-methylimidazole.