Study On Synthesis Of Marine Natural Product Exumolides

The cyclic peptide is a very important part of the peptides.Compared with the corresponding linear peptides,it has a relatively stable conformation,a better resistance to hydrolysis and a resistance to chemical degradation in vivo.Cyclic peptide ester is also an important nature.It comes from the cyclic peptide compound whose amide bond is replaced by ester bond in the structure.Exumolides A and B,obtained by Kelly M.Jenkins,are secondary metabolites from marine organisms.Experiments show that the two cyclic hexadepsipeptides have obvious anti-tumor activity.Its cell growth experiments in liquid environments found that they can inhibit the growth of the marine single-celled green plants Dunaliella sp.But so far,its total synthesis has not been reported.Their synthesis will be described in this paper.First of all,stereoselective synthesis of ?-hydroxy acids with the raw material of leucine,valine,phenylalanine and isoleucine was discussed.The general method is reasonable.Secondly,cyclic hexapeptide analogs of the natural marine hexadepsipeptides Exumolides A and B was designed.To its total synthesis,different condensing agents,solvents and synthetic routes was tried.The synthesis of non-natural amino acid N-methyl amino acid was studied.We got the ultimate success of the synthesis of the cyclic hexapeptide.On this basis,the synthetic route of the hexadepsipeptides was studied.Finally,the first synthesis of exumolide A and B was accomplished.The products were characterized by mass spectrometry(MS),nuclear magnetic resonance(NMR)and other spectral analysis to identify the structures.