Study On The Synthesis And Chiral Sepearation Of Ketone Derivatives And Alkyne,the Key Intermediates Of Lycopodium Alkalodis Lycopalhine A

In recent years,palhine class alkaloid,seperated from clubmosses by many teams from difference regions of China,were proved to belong to Lycopadium alkaloids with a cage three-dimensional structure.Because of the complex molecular structure,containing 9 chiral carbon atoms and eight consecutive adjacent to each other,eight rings forming a complex cage structure,more and more teams turned to the synthesis of palhine class alkaloid.Due to the lower Lycopalhine A cotent in natural clubmosses,the samples separated and purified were far from being desired for biological activity testing,then the clean,concise and efficient total synthesis is particularly important.The main work of this paper is focused on the synthesis and structure identification of ketene derivatives,a key intermediate in the synthesis of Lycopalhine A.The Pauson-Khand reaction was also studied in this paper.Determination of the optical purity of new chiral alkynes in strategic syntheses and bioorthogonal studies is always problematic.Chiral column HPLC method in general could not be directly used to resolve such substrates,since the differentiation of alkyne segment with other alkane/alkene segment is not significant on stationary phase,and alkyne group is not a good UV chromophore.Usually,a pre-HPLC derivation reaction with tedious workup procedure was needed.Making use of easily prepared,stable alkyne-Co-complexes,we developed a simple and general method by analysis the in situ generated cobalt-complex of chiral alkynes using chiral column HPLC.This new method is especially suitable for the alkynes without chromophores and other derivable groups.