Fostriecin (CI-920) To Phosphate Derivatives Asymmetric Synthesis

Fostriecin(CI-920) an antibiotic with novel phosphate ester structure showed against a broad spectrum of tumor cells both in vitro and in vivo test. There were four chiral centers (5R, 8R, 9R, 11R) in the molecule. A synthesis of the C₉S epimer of dephosphorylated Fostriecin from glucofuranose synthon had been reported by Geroge Just. In this thesis, a modified just's synthetic route of dephosphorylated Fostriecin was designed. The asymmetric synthesis of part I and part III and the synthesis of part II were realized. The link of three parts had also been tried.Part I was synthesized from disubstituted furan-2-one (I-4) through Swern oxidation, Wittig reaction and ring opening. Two synthetic routes for the preparation of intermediate I-4 had been studied. (1), Treatment of glyoxylate with propenyl silane afforded racemic α-hydroxylpentenate. Protection of hydroxyl group followed by Sharpless asymmetric dihydroxylation of double bond with successive ring closure gave a mixture of two diastereomers. Separation of the mixture gave expected furan-2-one (I-4, C₉R, C₁₁R) and its diastereomer (I-4', C₉S, C₁₁R). (2), Through intramolecular induction asymmetric synthetic route carried out chrial ligand 8-phenylmenthyl glyoxylate. Addition reaction of propene to 8-...