Synthesis and Conformational Analysis of 2′‐Deoxy‐2′‐(3‐methoxybenzamido)adenosine, a rational‐designed inhibitor of trypanosomal glyceraldehyde phosphate dehydrogenase (GAPDH)

A series of 2′‐benzamido‐2′‐deoxyadenosine analogues were synthesized in an effort to find new lead structures for the treatment of sleeping sickness. The 2′‐deoxy‐2′‐(3‐methoxybenzamido)adenosine ( 1h ) was proved to be a selective inhibitor of the parasite glyceraldehyde 3‐phosphate dehydrogenase which confirms the modeling studies. The solution‐state conformation of 2′‐(thiophene‐2‐carboxamido) analogue 1d demonstrates a 2′‐ endo conformation, an orientation of the thiophene ring under the ribose moiety, and the base part occupying a ‘ syn ’/‘ anti ’ equilibrium.