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. 2023 Apr 6:135:133330.
doi: 10.1016/j.tet.2023.133330. Epub 2023 Feb 23.

Synthesis of 4- O-(4-Amino-4-deoxy-β-D-xylopyranosyl)paromomycin and 4- S-(β-D-Xylopyranosyl)-4-deoxy-4'-thio-paromomycin and Evaluation of their Antiribosomal and Antibacterial Activity

Rukshana Mohamad-Ramshan  1 , Chennaiah Ande  2 , Takahiko Matsushita  1 , Klara Haldimann  3 , Andrea Vasella  4 , Sven N Hobbie  3 , David Crich  1   2   5   6
Affiliations

Synthesis of 4- O-(4-Amino-4-deoxy-β-D-xylopyranosyl)paromomycin and 4- S-(β-D-Xylopyranosyl)-4-deoxy-4'-thio-paromomycin and Evaluation of their Antiribosomal and Antibacterial Activity

Rukshana Mohamad-Ramshan et al. Tetrahedron. .

Abstract

The design, synthesis and antiribosomal and antibacterial activity of two novel glycosides of the aminoglycoside antibiotic paromomycin are described. The first carries of 4-amino-4-deoxy-β-D-xylopyranosyl moiety at the paromomycin 4'-position and is approximately two-fold more active than the corresponding β-D-xylopyranosyl derivative. The second is a 4'-(β-D-xylopyranosylthio) derivative of 4'-deoxyparomomycin that is unexpectedly less active than the simple β-D-xylopyranosyl derivative, perhaps because of the insertion of the conformationally more mobile thioglycosidic linkage.

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Conflict of interest statement

Declaration of Competing Interest. AV, SNH and DC are cofounders of and retain an equity position in Juvabis AG, a biotech start-up developing next generation aminoglycoside antibiotics. All other authors declare no competing interests. Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Apramycin, Saccharosin, Paromomycin 4’-Derivatives and the Target Molecules 6 and 10.
Figure 2.
Figure 2.
SAR Model for the Paromomycin 4’-Glycosides
Scheme 1.
Scheme 1.
Preparation of the 4-azido-4-deoxy-D-xylopyranosyl donor 15.
Scheme 2.
Scheme 2.
Synthesis of glycoside 6.
Scheme 3.
Scheme 3.
Synthesis of thioglycoside 10.
See this image and copyright information in PMC

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