Studies On Asymmetric Synthesis Of Polyhydroxy-α-Amino Acids And Total Synthesis Of (+)-Conagenin

Polyhydroxy-α-amino acids are an important class of amino acids due to their inherent biological activities and as structural components of more complex natural products possessing a wide range of biological activities. Polyhydroxy-a-amino acids have also been used as intermediates in the synthesis of other compounds, such as polyoxins and sphingofungins. So, the stereoselective synthesis of polyhydroxy-a-amino acids has opened new dimensions for both fundamental investigations and application potentials.Our method is based on the key chiral tricyclic iminolactone, as a glycine equivalent for asymmetric synthesis of amino acids. The template is derived from natural (1R)-(+)-camphor in four steps with good yield (overall yield >50%). The rigorous structure of camphor and special boat conformation of iminolatone make the aldol reaction possessing high diastereoslective (>98%) and high yield. Hydrolysis of the aldol product furnished the desired polyhydroxy-a-amino acids in good yields and high enantiomeric excesses with nearly quantitative recovery of the chiral auxiliary 2-exo-hydroxyepicamphor and 3 -exo-hydroxycamphor.Then, the key chiral tricyclic iminolactone was applied in the asymmetric total synthesis of natural product (+)-Conagenin. (+)-Conagenin, a low molecular weight immunomodulator, was discovered in fermentation broths of Streptomyces roseosporu -s. It is an immunomodulator of antitumor activity stimulating activated T cells and enhancing generation of antitumor cells. Also, it may be useful in cancer chemotherap -y. This substance posseses three contiguous chiral centers and a (S)-methylserine moiety containg a quaternary stereocenter. Taking most advantage of successful methods of synthesizing a-amino acids, we designed a short practicable route that the methyl (S)-methylserine was synthesized starting from the tricyclic iminolactone for in steps with high diastereoslective and high yield.