Synthesis and biological evaluation of a bicyclo[4.1.0]heptyl analogue of glucose-1-phosphate

摘要

The synthesis of a bicyclo[4.1.0]heptyl analogue of glucose-1-phophate, (lR,2R,3S,4S,5S,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)-bicyclo[4.1.0]heptan-2-yl dihydrogen phosphate (5) is reported. The synthetic route chosen started with methyl alpha-D-glucopyranoside and was accomplished in 11 steps with an overall yield of 3 percent. Compound 5 was tested as a potential substrate of UTP: alpha-D-glucose-l-phosphate uridylyltransferase, the enzyme that converts glucose-1-phosphate into UDP-glucose. However, the conformationally restricted glucose-1-phosphate analogue 5 was found to be a weakly binding inhibitor, rather than a substrate, of the yeast transferase (12 percent inhibition at a concentration of 0.1 mmol L~(-1)).