The Asymmetric Synthesis Of Polyhydroxy Pyrrolizidine Alkaloid7a-epi-hyacinthacine A₁

The total synthesis of natural products is an intersectional science, which involvesbroader domain and has grand challenge. It is not only the concentrated reflection of theorganic synthetic level, but also an important pathway to discover new reactions and methods.Total synthesis of natural products plays significant role in drug research and development.From1990s, with the significant development of asymmetric synthesis, the total synthesis ofcomplex natural products has been an unprecedented active field.The polyhydroxy pyrrolizidine alkaloids, which widely distributed in plants, representimportant biological activities. There are multiple chiral centers in these alkaloids. Thechanges of either the stereochemistry of the skeleton or the positions of hydroxyl groups willchange the activities. Therefore, the asymmetric synthesis of polyhydroxy pyrrolizidinealkaloids remains a major challenge to synthesis chemists since they were found.In recent years, our group has used cheap amino acids as the chiral starting unit toasymmetric synthesis of both small molecules alkaloids with bioactivities and marine naturalproducts with large ring lactone. The method of synthesis of （2S,3S,4S）-3,4-dihydroxyhydroxymethylimines （139） starting with D-Glu was successfully founded, simultaneously.Based on this method, the thesis mainly studied two parts which are listed below:1. Compound cis-142with single configuration was synthesized with the high selectivityon C₂in N,O-acetal141allylation with allyltrimethylsilane under-78°C, catalyzed withLewis acid （BF₃·Et₂O）. The configulation of allylated compound was determined by NOEspectrum.2. Completed the asymmetric synthesis of compound7a-epi-hyacinthacine A₁.