Flow chemistry based catalytic hydrogenation for improving the synthesis of 1-deoxynojirimycin (DNJ) from an l-sorbose derived precursor

1-Deoxynojirimycin (1-DNJ) is a glycoprocessing inhibitor, and it serves as a synthetic precursor to two of three currently marketed iminosugar drugs, miglustat (N-butyl DNJ/Zavesca®) and miglitol (Glyset®). Herein a continuous flow procedure is presented that shortens a synthesis of 1-DNJ from an i...

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Bibliographic Details
Published in:Carbohydrate research 2023-07, Vol.529, p.108845-108845, Article 108845
Main Authors: Bennett, Jack J., Murphy, Paul V.
Format: Article
Language:English
Subjects:
Flow chemistry
Glycomimetic
Hydrogenation
Iminosugar
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Summary:1-Deoxynojirimycin (1-DNJ) is a glycoprocessing inhibitor, and it serves as a synthetic precursor to two of three currently marketed iminosugar drugs, miglustat (N-butyl DNJ/Zavesca®) and miglitol (Glyset®). Herein a continuous flow procedure is presented that shortens a synthesis of 1-DNJ from an intermediate prepared from l-sorbose. Batch reactions involving an azide reduction, subsequent reductive amination-based cyclisation, and O-benzyl deprotection in a previous report required two steps and the use of an acid. Here, this sequence is achieved in one step using the H-Cube® MiniPlus continuous flow reactor. Subsequent reductive amination of 1-DNJ with butanal using the H-Cube® gave NB-DNJ. [Display omitted] •Continuous flow synthesis of 1-DNJ from an l-sorbose derivative.•Improved yield, reaction time and safety.•First flow synthesis of miglustat (Zavesca®).
ISSN:0008-6215
1873-426X
DOI:10.1016/j.carres.2023.108845