Alkylation of alcohols, amines, thiols and their derivatives by cyclic sulfate intermediates

US6277982A · kind A · utility

Assignee

• Isis Pharmaceuticals, Inc. · US

Inventors

• Allister S. Fraser · Encinitas, US
• Muthiah Manoharan · Carlsbad, US
• Phillip Dan Cook · Carlsbad, US
• Michael E. Jung · Los Angeles, US
• Andrew M. Kawasaki · Oceanside, US

Key dates

• Filing date: Aug 20, 1999
• Grant date: Aug 21, 2001
• Expiry date: Aug 20, 2019

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07H21/00
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

Methods for the alkylation of alcohols, amines and thiols by the use of cyclic sulfates are disclosed. The alkylated sulfates formed are versatile intermediates which may be further elaborated by methods of the invention. In particular, methods for the alkylation of the 2', 3' or 5'-hydroxy position of nucleosides and nucleoside analogs with cyclic sulfates to form the 2', 3' or 5'-O-alkyl sulfate modified compounds are disclosed. Displacement of the 2',3' or 5'-O-sulfate with a nucleophile provides 2', 3' or 5'-O-modified nucleosides and nucleoside analogs useful for the synthesis of oligomeric compounds having improved hybridization affinity and nuclease resistance.