Synthetic Studies on Oligosaccharides, Carbohydrate Containing Triazoles and NBased Heterocycles of Biological Importance

Efficient synthesis of 1,4-disubstituted triazolyl N-carboxamides via a simple and convenient MCR using basic alumina as solid support. Glucose-based inhibitors with NHCO as linker between the sugar and the aromatics showed potent activity against glycogen phosphorylase which is a validated target against type 2 diabetes mellitus. Successful bio-isosteric modification of the amide with different heteroaromatic compounds leading to compounds having better inhibition properties is also known. These motivated us to synthesize a library of compounds where sugar moieties were linked to 1,2,3-triazoles by NHCO bonds and a long hydrophobic chain using a novel and an environmentally benign chemical process. The long linking arm is likely to make the sugar moiety available for better binding with the appropriate receptor. The synthesis of triazolyl N-carboxamides using traditional methods is a three-step process. Firstly, the aliphatic or aromatic azides are synthesized followed by the coppermediated azide–alkyne cyclization. Finally, the amide or ester linkages are formed. The traditional chemical synthesis requires extensive chromatographic purification of intermediates, which is tedious and time consuming. The new protocol developed by us allows domino Ullmann-type reaction, Click reaction and formation of ester or amidelinkages in a single reaction vessel using Cu(phen)(PPh3)Br as catalyst and chloro-phenylthio- methylene-dimethylammonium chloride (CMPA) as coupling agent using basic alumina as solid support (Scheme 1)