STUDIES ON RUBIA AKANE (RA) DERIVATIVES .8. DESIGN, SYNTHESES AND ANTITUMOR-ACTIVITY OF CYCLIC HEXAPEPTIDE RA ANALOGS POSSESSING AN ALKYL SUBSTITUENT ON THE TYR-3 AROMATIC RING

The effective conversion of RA-VII 1 into the naturally less-accessibl e RA-II 4 has been devised through boron tribromide bis-O-demethylatio n and successive selective partial O-methylation using diazo(trimethyl silyl)methane. The O-triflate 11 prepared from RA-II 4 was subjected t o cross-coupling reaction with alkylstannanes to produce analogues 12, 13 and 15, while compounds 13 and 15 were later converted into analog ues 14 and 16, respectively. Analogues 12-16 showed antitumour activit y against P-388 leukaemia both in vitro and in vivo.