Synthesis of acyclic galactitol- and lyxitol-aminophosphonates as inhibitors of UDP-galactopyranose mutase

UDP-galactopyranose mutase (UGM) catalyzes the isomerization of UDP-galactopyranose (UDP-Galp) into UDP-galactofuranose (UDP-Galf), an essential step of the mycobacterial cell wall biosynthesis. Acyclic alditol-aminophosphonates in the d-galactose and d-lyxose series were designed as mimics of high energy intermediates of the UGM catalyzed isomerization. Interestingly, the d-lyxitol-aminophosphonate displayed better inhibition properties than the d-galactitol-aminophosphonate.

Acyclic alditol-aminophosphonates 1 and 2 were designed as mimics of high energy intermediates of the UGM catalyzed isomerization. Interestingly, the d-lyxitol-aminophosphonate 2 displayed better inhibition properties than 1.