Synthesis of gemcitabine and it's tetrafluorinated analogues

A novel synthesis of the 2-deoxy-2,2-difluorocytidine nucleoside analogue gemcitabine has been achieved. Starting from the known 3,5-O-dibenzoyl-2- deoxy-2,2-difluororibose, the nucleobase moiety is constructed in a linear fashion, using amino- or urea glycosylation methodology. This methodology has also been employed to synthesise nucleosides containing a tetrafluorinated ribose sugar and has been compared to conventional convergent nucleobase introduction methods. In this respect, a high-yielding Mitsunobu-based protocol has also been developed. Both purine and pyrimidine analogues have been synthesised. The aminoglycosylation methodology has been investigated with a range of amines. The methodology proves high-yielding for primary amines and lesshindered secondary amines. In contrast to expectations, their stability in acidic media was not very high. Anomerisation and ring isomerisation studies have been conducted

Name dc:type.qualificationname

Ph.D.

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of Southampton

Year dc:date.issued

2011

Author dc:creator

• Brown, Kylie J.

Advisor dc:contributor.advisor

• Linclau, Bruno