Method For The Preparation Of Intermediates Of Fondaparinux Sodium

In this dissertation, a novel synthetic route for the synthesis of three keyintermediates (monomer A, C and E) of Fondaparinux sodium is described.Fondaparinux sodium is a selective inhibitor of Xa, an anticoagulantnon-covalently binds to the active site of antithrombin, specifically, resulting in rapidinhibition of Xa and subsequent reduction of thrombin and fibrin formation.Fondaparinux sodium is currently marketed in France, UK, Germany, China and USAfor the treatment and prevention of deep venous thrombosis.The novel synthetic methodology was developed using glucose as the cheapstarting reagent to finish the common intermediate that can be used for the preparationof monomer A, C and E. This method consists of a total of seventeen step synthesis,including acetylation, thiocresol replacement at C1position, de-acetylation,4,6-benzoyl acetal protection, C3-selective benzoyl protection, oxidation OF C2-hydroxyl group, stereo-selective reduction which results in structural conversion ofglucose to mannose, finally after a few steps, the transformation of C2-hydroxyl intoazide to afford the common intermediate. With this intermediate, monomer A, C or Ewere synthesized in a2to4-step process. This synthetic strategy using glucose forsynthesis of Beta-mannose amino-glucosinolates not only reduced the reported twentysix step synthesis for these3carbohydrate building blocks, but also avoided usingexpensive mannose and aminoglucose as the raw materials.