Studies Toward the Synthesis of Inhibitors of Mycobacterium tuberculosis Cell-Wall Biosynthesis: The Assembly of Triazole-Linked 1,6-α-d-Oligomannosides via Click CuAAC

Abstract

A versatile synthesis of 1,6-α-d-oligomannosides featuring the 1,4-disubstituted triazole ring as interglycosidic tether is presented via iterative copper(I)-catalyzed azide-alkyne cycloaddition. Free hydroxy hexamannoside and decamannoside featuring a capping 6-deoxymannose fragment have been prepared and characterized.

Key words

alkynes - azides - copper - cycloadditions - stereoselective synthesis

References and Notes

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11

The building block employed in the earlier synthesis was an ethynyl α-d-C-mannoside. Therefore, each cycle was constituted of the click azide-alkyne reaction and then transformation of the 6-hydroxy into azido group in the resulting product.

12

It has to be noted that attempts to synthesize compound 4 by addition of acetone to ethynyl 6-azido-2,3,4-tri-O-benzyl-6-deoxy-α-d-C-mannopyranoside failed in our hands. The basic conditions required for this process induced the 1,2-elimination of benzyl alcohol leading to the undesired glycal.

14

Compound 9 in ref. 7 was treated with diphenylphosphoryl azide (DPPA) and DBU under microwave irradiation (120 ˚C, 2 h) to give 11 in 78% isolated yield (see Supporting Information).