On the Way to Glycoprocessing Inhibitors − Synthesis of an Imidazolo‐Nectrisine‐Phosphono Acid Derivative: A Potential Glycosyltranferase Inhibitor

Assuming the transition state of glycosyltransferase inhibitors to be similar to those encountered with potent glycosidase inhibitors − i.e. a flattened conformation with a positively charged anomeric centre − we worked out a synthesis of the D ‐ arabino ‐configured phosphonic acid target molecule 2 derived from an imidazolo‐sugar. The key synthetic intermediate is the linear imidazolo L ‐ xylo compound 10 which could be obtained, either from L ‐ threo precursor 6 by a coupling reaction with imidazole derivative 5 , or from L ‐sorbose. A multi‐step and site specific iodination of 10 gave the mono‐iodo‐ L ‐ xylo derivative 14 which was cyclised to the D ‐ arabino ‐configured bicyclic azasugar 15 . Phosphorylation of the Grignard derivative of the latter, followed by mono‐esterification with citronellol along with some protection‐deprotection steps led to target molecule 2 . The potential inhibitor 2 is supposed to be protonated at its most basic N atom by a carboxylic acid residue in the arabinosyl‐transferase active site. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)