Synthesis of Antitumor\nBicyclic Hexapeptide RA-VII\nAnalogues Possessing an Aromatic Amino Acid at Residue 2

RA-III\nacetate was treated with Lawesson’s\nreagent\nto afford\n[Tyr-3-Ψ(CS-NH)-Ala-4]RA-III acetate. Treatment of this product\nwith Hg(OAc)<sub>2</sub>/Li<sub>2</sub>CO<sub>3</sub> and then methanol\ngave an oxazole intermediate. Acid-catalyzed arylation of the methylene\ncarbon atom on the oxazole ring and subsequent partial hydrolysis\nof the oxazole ring in the resultant compounds afforded RA-VII analogues\nhaving an aromatic amino acid at residue 2. [5-Fluoro-d-Trp-2]RA-VII\nshowed IC<sub>50</sub> values of 0.038 and 0.077 μM against\nthe HL-60 and HCT-116 cell lines, respectively.