Synthesis of arabinose glycosyl sulfamides as potential inhibitors of mycobacterial cell wall biosynthesis

• Synthesis of a variety of glycosyl sulfamides of arabinose.
• Assays of anti-mycobacterial activity using Mycobacterium smegmatis.
• Optimal activity (MIC 62 μg/mL) observed for a sulfamide with a C10 alkyl chain.

A series of arabinose glycosyl sulfamides with varying alkyl chain types and lengths were synthesised as mimics of decaprenolphosphoarabinose (DPA), and as potential inhibitors of mycobacterial cell wall biosynthesis. Unprecedented conversion of the desired furanose to the thermodynamically more stable pyranose form occurred during final de-protection. Biological testing against Mycobacterium smegmatis revealed low to moderate anti-mycobacterial activity with marked dependence on alkyl chain length, which in the case of mono-substituted sulfamides was maximal for a C-10 chain.

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