Cyclo-[(gly) Thz-Pro-Leu-Val-(L&D)-(gln) Thz] (2) was synthesized. In this process
the thiazole amino acid
z-(L&D)(gln)ThzOH (6)
was obtained by directly condensing a thioamide with bromopyruvic acid; the formation of peptide bond was carried out with DCC and azide methods and the cyclzation with DPPA in high dilution (10
-3
-10
-4
M). The product has mp. 180-186℃ (uncorr.)
[α]
D
19
-28.9℃(c 0.19
EtOH). 2 is structurally similar but not identical to Dolastatin-3. The preliminary physiological activity test shows that 6 has an effect of inhibiting lung cancer A-549 cell in concentration at 30-50μg/ml and 2 in 10-30μg/ml
and z-(gly)Thz-Pro-Leu-ValOH has not such activity. In addition
the preparation of γ-benzyl glutamate was improved.