Issue 9, 2002

Synthesis and investigation of L-fuco- and D-glucurono-azafagomine

Abstract

The new azasugars (3S,4R,5S)-4,5-dihydroxy-3-methylhexahydropyridazine (3, azafucofagomine) and (3S,4R,5R)-4,5-dihydroxyhexahydropyridazine-3-carboxylic acid (4, azaglucuronofagomine) were synthesised. Azafucofagomine (3) was made from D-ribose in ten steps in a synthesis that involved partial 2,3-protection, deoxygenation of the 5-OH, reductive amination with tert-butyl carbazate, mesylation, cyclisation and deprotection. Compound 4 was made from L-xylose in 12 steps in a related way starting with 2,3,5-protection, reductive amination with tert-butyl carbazate, mesylation and cyclisation. The key step in this synthesis is selective debenzylation of a primary benzyl ether with acetyl bromide to produce a partially benzylated hexahydropyridazine that was oxidised to the acid and deprotected. The 3-, 4- and 6-deoxy analogues of azafagomine [1, (3R,4R,5R)-4,5-dihydroxy-3-hydroxymethylhexahydropyridazine] were also made. Compounds 3 and 4 were shown to be potent α-fucosidase and β-glucuronidase inhibitors, respectively.

Graphical abstract: Synthesis and investigation of L-fuco- and D-glucurono-azafagomine

Supplementary files

Article information

Article type
Paper
Submitted
23 Jan 2002
Accepted
21 Mar 2002
First published
12 Apr 2002

J. Chem. Soc., Perkin Trans. 1, 2002, 1190-1198

Synthesis and investigation of L-fuco- and D-glucurono-azafagomine

H. H. Jensen, A. Jensen, R. G. Hazell and M. Bols, J. Chem. Soc., Perkin Trans. 1, 2002, 1190 DOI: 10.1039/B200884J

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Spotlight

Advertisements