A linear synthesis of gemcitabine

Kylie Brown; Alex Weymouth-Wilson; Bruno Linclau

doi:10.1016/j.carres.2015.01.001

A linear synthesis of gemcitabine

Carbohydr Res. 2015 Apr 10:406:71-5. doi: 10.1016/j.carres.2015.01.001. Epub 2015 Jan 14.

Authors

Kylie Brown¹, Alex Weymouth-Wilson², Bruno Linclau³

Affiliations

¹ Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK; Dextra Laboratories Ltd, The Science and Technology Centre, Earley Gate, Whiteknights Road, Reading RG6 6BZ, UK.
² Dextra Laboratories Ltd, The Science and Technology Centre, Earley Gate, Whiteknights Road, Reading RG6 6BZ, UK.
³ Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK. Electronic address: bruno.linclau@soton.ac.uk.

PMID: 25681996
DOI: 10.1016/j.carres.2015.01.001

Abstract

Gemcitabine, 2'-deoxy-2',2'-difluorocytidine, is currently prescribed against a number of cancers. Here we report a linear synthesis of gemcitabine with a high-yielding direct conversion of 3,5-di-O-benzoyl-2-deoxy-2,2-difluororibose into the corresponding glycosyl urea as the key step, followed by conventional conversion to the cytosine base via the uracil derivative. The process proceeded with modest anomeric selectivity.

Keywords: Fluorinated nucleoside; Gemcitabine; Glycosyl urea; Linear nucleoside introduction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acylation
Antimetabolites, Antineoplastic / chemical synthesis*
Catalysis
Cyclization
Deoxycytidine / analogs & derivatives*
Deoxycytidine / chemical synthesis
Gemcitabine
Urea / chemistry

Substances

Antimetabolites, Antineoplastic
Deoxycytidine
Urea
Gemcitabine