Synthese von DD‐Heptosephosphaten als Substrate oder potentielle Inhibitoren für die Heptose‐Synthetase

Abstract

Synthesis of DD‐Heptose Phosphates as Substrates or Potential Inhibitors for the Heptose SynthetaseA synthesis of D‐glycero‐D‐manno‐heptose (DD‐Hep) via an inversion of L‐glycero‐D‐manno‐heptose (LD‐Hep) is described. Starting from DD‐Hep the α‐1‐phosphate 3 and the α‐1‐methylphosphonate 30 were synthesized. Furthermore, the α‐1‐dialkyldithiophosphate esters from DD‐Hep were prepared. The 2,3,4,6, 7‐penta‐O‐benzyl‐D‐glycero‐α‐D‐ manno‐heptosyl trichloroacetimidate (22) turned out to be a very successful glycosyl donor in the reaction with the phosphate esters. The amidophosphates 41 and 42 of DD‐Hep have been synthesized according to the Staudinger reaction using glycosyl azides of DD‐Hep and tribenzyl or tributyl phosphite. The modified phosphates represent potential inhibitors for the heptose synthetase, an enzyme of the biosynthesis of the inner core region of lipopolysaccharides. Reaction of the phosphate 3 with AMP morpholidate afforded ADP‐DD‐Hep 4 which represents the product of the heptose synthetase enzyme reaction. magnified image