An all-L configuration reverse order of peptide bonding possibility for the cell growth inhibitory (PS system) cyclic peptide dolastatin 3 was eliminated by synthesis of thiazole amino acid containing peptide 2. By employing a series (Scheme I) of mixed carbonic anhydride (except for 9 →11 where DCCI-HBT was used) peptide bond forming reactions with N-Boc protection and a 2,4,5-trichlorophenol active ester cyclization step, cyclic pentapeptide 2 was obtained as a mixture of diastereomers corresponding to the (R)- and (S)-(gln)Thz unit. The thiazole amino acid components were synthesized employing a Hantzsch reaction as the key step (cf. Scheme II). Spectral analysis of the individual (R)- and (S)-(gln)Thz cyclic pentapeptide 2 removed both as structural candidates for dolastatin 3.
ASJC Scopus subject areas
- Organic Chemistry