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.

Synthesis and evaluation of galactofuranosyl N,N-dialkyl sulfenamides and sulfonamides as antimycobacterial agents.

The recent emergence of clinically oppressive superbugs, some with resistance to nearly all frontline drug therapies, has challenged our ability to combat such infectious organisms as Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). Our medicinal chemistry program targeting this pathogen has identified several potent galactofuranose-based in vitro inhibitors of mycobacterial growth. The most potent compound, the Galf N,N-didecyl sulfenamide 8d, displayed anti-mycobacterial activity (MIC) of 1 microg/mL in a cell based assay against a representative strain of Mycobacterium smegmatis.