DESIGN AND SYNTHESIS OF NEOCARZINOSTATIN ANALOGS

The first generation of 10 membered ring analogues (11 approximately 13) of the neocarzinostatin chromophore (1) could undergo the thiol or radical triggered Masamune-Bergman type cycloaromatization, but they were not able to show the antibiotic nor antitumor activities. New analogues (27 approximately 29) of the second generation exhibited the remarkable DNA cleaving activities as well as the biological activities. The unprecedented guanine specific DNA cleavage by the simple chiral alcohol 28 is striking, while the complex of the possible intercalator 29 with the neocarzinostatin apoprotein (2) did not show an evident specificity.