A multi-component reaction approach to the synthesis of potent antidiabetic agents five-membered iminosugars analogues

Original Article

JOURNAL 1765

Organic Communications

VOLUME & ISSUE

Year: 2020 Issue: 3 July-September

PAGES

p.79 - 88

DOI ADDRESS

http://doi.org/10.25135/acg.oc.85.20.08.1765

STATISTICS

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AUTHORS

Agustono Wibowo
Zurina Shaameri
Mohd Fazli Mohammat
Ahmad Sazali Hamzah

GRAPHICAL ABSTRACT

ABSTRACT

Some novel five-membered iminosugar analogues were efficiently synthesized via the MCRs of three components; amines, aldehydes and oxaloacetate to give 4-hydroxymethylpyrrolidines. Reduction of 3-hydroxy-4-carbomethoxy-3-pyrroliden-2-ones with Pd/C-catalyzed hydrogenation gave the corresponding cis-hydrogenated products at C3/C4 stereoselectively. Then following reductions of ester and amide functionalities with LiAlH4 afforded 4-(hydroxymethyl)pyrrolidin-3-ols. Among the synthesized compounds 4-hydrazineyl-3-hydroxymethyl-2-(4-methoxyphenyl)-N-methylpyrrolidine and 3-hydrazineyl-4-hydroxymethyl-1-methylpyrrolidine were found to be the most promising a-glucosidase inhibitor with IC50 values of 1.12 and 1.17 mM, respectively.

KEYWORDS

Iminosugar
pyrrolidine
one-pot reaction
stereoselective hydrogenation
antidiabetic