Bafilomycin analogue site-specifically fluorinated at the pharmacophore macrolactone ring has potent vacuolar-type ATPase inhibitory activity

[Display omitted] •Fluorinated bafilomycin analogue at C2 position of macrolactone ring was synthesized.•The synthesized analogue shows V-ATPase inhibitory activity comparable to natural product.•This is the first bioactive bafilomycin analogue with the modified pharmacophore macrolactone core. Base...

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Bibliographic Details
Published inTetrahedron letters Vol. 57; no. 22; pp. 2426 - 2429
Main Authors Tsuchikawa, Hiroshi, Hayashi, Tatsuru, Shibata, Hajime, Murata, Michio, Nagumo, Yoko, Usui, Takeo
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier Ltd 01.06.2016
Elsevier
Subjects
Bafilomycin
Chemical synthesis
Chemistry
Chemistry, Organic
Conformational analysis
Fluorine-label
Physical Sciences
Science & Technology
V-ATPase
Fluorine-label
Bafilomycin
V-ATPase
Chemical synthesis
Conformational analysis
KETONES
SUBUNIT-C
V-ATPASES
BAFILOMYCIN/CONCANAMYCIN-BINDING-SITE
MODEL
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Summary:[Display omitted] •Fluorinated bafilomycin analogue at C2 position of macrolactone ring was synthesized.•The synthesized analogue shows V-ATPase inhibitory activity comparable to natural product.•This is the first bioactive bafilomycin analogue with the modified pharmacophore macrolactone core. Based on previously reported structure–activity relationships, an analogue of bafilomycin A1 with a site-specific fluorine label at the C2 position was designed and efficiently synthesized. The fluorinated compound exhibited potent vacuolar-type ATPase (V-ATPase) inhibitory activity, comparable to that of the natural product, representing the first example of highly bioactive analogues with a modified macrolactone core from the plecomacrolide family compounds.
ISSN:0040-4039
1873-3581
DOI:10.1016/j.tetlet.2016.04.075