Structural Transformation Of The Marine Natural Cyclic Peptide Leucamide A Key Fragment

Leucamide A, a bioactive cyclic heptapeptide containing a unique mixed 4,2-bisheterocycle tandem pair consisting of a methyloxazole and thiazole subunit was first isolated from Australian marine sponge Leucetta microraphis. Leucamide A is characterized by the presence of seven amino acids and amino acid derived residues: L-leucine, oxazole, L-alanine, methyl-oxazole, thiazole, L-valine, and L-proline. Leucamide A was found to inhibit moderately the growth of the three tumor cell lines HM02, HepG2, and Huh7. Many compounds known to contain bisheterocycle tandem pair have remarkably potent biological activity which is related with the location and structure of the moieties. Such as MccB17, antitumor antibiotics Bleomycins.From the above, We show great interest in Leucamide A. Not only because of the structure of cyclic heptapeptide but also the unique methyloxazole and thiazole subunit which may be contributed to the further structure modification to find highly active compounds.Following the first total synthesis of Leucamide A accomplished by this group, Several small molecular library focusing on the 4,2-bisheterocycle tandem pair substructure were constructed and some compounds show anti-virus activity on influenza A, HBV and HIV IN. The modification from the amino functionality of the 4,2-bisheterocycle tandem pair substructure. 15 new compounds were obtained, in which 8 compounds show certain activity . The modification on the compound 6, compound 11 and compound 12 from three various locations (R1, R2, R3).18 new compounds were obtained. 5 analogues of Leucamide A were prepared by replacing the dipeptide Pro-Leu of Leucamide A with various amino acid with 2-6 carbon.