Study On Synthesis Of Natural Marine Peptide Tasiamide

Retrosynthetic analysis and study on Chemical synthesis of natural marine peptide Tasiamide were described in this paper.N-Me-D-Phe and N-Me-L-Gln were synthesized firstly.N-Boc-Me-D-Phe were obtained from D-Phe through N-protection with Boc and N-methylation with NaH/CH3I in an overall yield of 83%. N-Cbz-Me-D-Phe were obtained from D-Phe through N-protection with Cbz and N-methylation with NaH/CH3I in an overall yield of 85%. The glutamine's amine group was protected with the benzyloxycarbonyl group. The glutamine amide side chain was protected with the trityl group under acidic conditions. N-Cbz-Me-Gln(Trt) was converted into the corresponding oxazolidinone by reaction with paraformaldehyde. Reduction cleavage of the oxazolidinone with trifluoroacetic acid/triethylsilane gave N-Cbz-Me-Gln in an overallyield of 43%。L-Pro-OMe·HCl from L-Pro through esterification was coupled with N-Boc-Me-D-Phe via PyAOP activation to yield dipeptide N-Boc-Me-D-Phe-Pro-OMe. Removing of the Boc protecting group of the dipeptide and coupling with N-Cbz-Gly via BOP-Cl gave the tripeptide N-Cbz-Gly-N-Me-D-Phe-Pro-OMe in...