The first total synthesis of RA-VII and deoxybouvardin(RA-V) is described. The synthetic strategies are shown in Chart II. Among them, Route A was only successful. It comprises construction of the 14-membered ring unit 3 and subsequent coupling with tetrapeptide 4. For the construction of the 14-membered ring, which is crucial to this strategy and should be versatile intermediate leading to related compounds, we employed two methods, Route A-1 and A-2. A-1 is intramolecular amidation of linear diphenyl ether 13 (Scheme I). A-2 is intramolecular oxidative coupling of two phenolic parts of dipeptide by thallium trinitrate (Table I, II). A-1 did not give 14-membered ring but dimeric 28-membered one. A-2 afforded 14-membered rings. Thus the oxidation of dichloro dibromo derivatives 20 gave the desired 14-membered ring 23. But tetrabromide 17 was found to cyclize in the opposite fashion comparing with RA. Conversion of 23 to RA-VII was achieved by the successive treatment illustrated in Scheme III and IV. Selective demethylation of RA-VII with AlCl_3 gave deoxybouvardin (RA-V). Other strategies, via 18- and 26-membered ring (Route B and C) are also reported (Chart I).
