Synthesis and biological evaluation of galactofuranosyl alkyl thioglycosides as inhibitors of mycobacteria.
As part of our research interest directed toward the development of antimycobacterial agents, we have investigated compounds based on galactofuranose (Galf), an essential cell wall component of mycobacteria. The objective of this study was to explore structure activity relationships of Galf thioglycosides with straight chain and branched aglycons. Acylated Galf 9-heptadecyl thioglycoside was prepared by Lewis acid-catalyzed thioglycosidation of 1,2,3,5,6-penta-O-acyl-D-galactofuranose with 9-heptadecanethiol, and subsequently converted to the corresponding sulfone using m-CPBA. Both Galf 9-heptadecyl thioglycoside and sulfone displayed in vitro inhibition (MIC) of the growth of Mycobacterium smegmatis below 5 microg/mL, while Galf 1-octyl thioglycoside gave no inhibition at or below 32 microg/mL.
Davis
Chris B
CB
Institute for Glycomics, Griffith University (Gold Coast Campus), PMB 50 Gold Coast Mail Centre, Queensland 9726, Australia.
Hartnell
Regan D
RD
Madge
Paul D
PD
Owen
David J
DJ
Thomson
Robin J
RJ
Chong
Andrew K J
AK
Coppel
Ross L
RL
von Itzstein
Mark
M
D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D005690:Galactose; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D009161:Mycobacterium / Q000187:drug effects*; D013450:Sulfones; D013816:Thermodynamics; D013865:Thioglycosides / Q000138:chemical synthesis* / Q000494:pharmacology*
D000995:Antitubercular Agents; D007202:Indicators and Reagents; D013450:Sulfones; D013865:Thioglycosides; D005690:Galactose