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. 2020 Nov 19;18(11):572.
doi: 10.3390/md18110572.

Toward the Identification of Novel Antimicrobial Agents: One-Pot Synthesis of Lipophilic Conjugates of N-Alkyl d- and l-Iminosugars

Anna Esposito  1 , Daniele D'Alonzo  1 , Stefano D'Errico  2 , Eliana De Gregorio  3 , Annalisa Guaragna  4
Affiliations

Toward the Identification of Novel Antimicrobial Agents: One-Pot Synthesis of Lipophilic Conjugates of N-Alkyl d- and l-Iminosugars

Anna Esposito et al. Mar Drugs. .

Abstract

In the effort to improve the antimicrobial activity of iminosugars, we report the synthesis of lipophilic iminosugars 10a-b and 11a-b based on the one-pot conjugation of both enantiomeric forms of N-butyldeoxynojirimycin (NBDNJ) and N-nonyloxypentyldeoxynojirimycin (NPDNJ) with cholesterol and a succinic acid model linker. The conjugation reaction was tuned using the established PS-TPP/I2/ImH activating system, which provided the desired compounds in high yields (94-96%) by a one-pot procedure. The substantial increase in the lipophilicity of 10a-b and 11a-b is supposed to improve internalization within the bacterial cell, thereby potentially leading to enhanced antimicrobial properties. However, assays are currently hampered by solubility problems; therefore, alternative administration strategies will need to be devised.

Keywords: antibacterial iminosugars; cholesterol; lipophilic iminosugars; polymer-supported triphenyl phosphine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Marketed iminosugar drugs.
Figure 2
Figure 2
Naturally occurring iminosugars with antimicrobial properties.
Figure 3
Figure 3
N-alkyl d- and l-iminosugars as antimicrobial agents against S. aureus.
Scheme 1
Scheme 1
Selectivity (COOH vs. OH) in the TPP/I2/ImH reaction.
Scheme 2
Scheme 2
Stepwise and one-pot routes to iminosugar conjugates 10a–b and 11a–b.
See this image and copyright information in PMC

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