Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate.
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Authors
Iqbal, Amjid
Sahraoui, El-Habib
Leeper, Finian J
Abstract
An analogue of thiamine having a furan ring in place of the thiazolium ring has been synthesised by a short and efficient route, involving gold(I)-catalysed cyclisation of an alkynyl alcohol to form the furan ring. The furan analogue of thiamine diphosphate (ThDP) was also made and tested for binding to and inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis (overexpressed in E. coli with a N-terminal His-tag). It is a very strong inhibitor, with a K i value of 32.5 pM. It was also shown that the furan analogue of thiamine can be functionalised at the C-2 position, which will allow access to mimics of reaction intermediates of various ThDP-dependent enzymes.
Description
Keywords
furan synthesis, gold-catalysed cyclisation, pyruvate decarboxylase, thiamine diphosphate
Journal Title
Beilstein J Org Chem
Conference Name
Journal ISSN
1860-5397
1860-5397
1860-5397
Volume Title
10
Publisher
Beilstein Institut
Publisher DOI
Sponsorship
This work was supported by a studentship from the Cambridge Commonwealth Trust (A.I.)