Practical synthesis of potent sphingosine-1-phosphate lyase inhibitors THI and LX2931

A practical and scalable synthesis of in vivo sphingosine-1-phosphate lyase inhibitor LX2931 (1) is described. The synthetic route features an improved Büchi cyclocondensation of 2-ethoxyacrylonitrile (3) with either 1-amino-1-deoxy-d-fructose acetate (4a) or d-(+)-glucosamine hydrochloride (4b) to...

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Bibliographic Details
Published in:Tetrahedron 2013-05, Vol.69 (20), p.4041-4046
Main Authors: Zhang, Haiming, Yan, Jie, Bednarz, Mark S., Hernandez, Gonzalo, Lu, Yuelie, Courtney, Lawrence F., Chen, Jason, Hu, Weifeng, Liu, Renmao, Yang, Xiaogen, Wu, Wenxue
Format: Article
Language:English
Subjects:
Acetates
Cyclocondensation
Fructosamine
Glucosamine
Hydrochlorides
Inhibitors
Isomerization
Oxime isomerization
Oximes
Sphingosine-1-phosphate
Synthesis
Tetrahedrons
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Summary:A practical and scalable synthesis of in vivo sphingosine-1-phosphate lyase inhibitor LX2931 (1) is described. The synthetic route features an improved Büchi cyclocondensation of 2-ethoxyacrylonitrile (3) with either 1-amino-1-deoxy-d-fructose acetate (4a) or d-(+)-glucosamine hydrochloride (4b) to produce 1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone (2, THI), followed by oximation of THI and acid-promoted oxime isomerization to give LX2931 (1). [Display omitted]
ISSN:0040-4020
1464-5416
DOI:10.1016/j.tet.2013.03.071