Studies on the Synthesis of Dynemicin Analogues and their Reaction Mechanisms

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Dynemicins possessing the characteristic cis-hex-3-ene-1,5-diynyl group have attracted considerable attention due to the generation of a phenylene biradical which is responsible for DNA strand scission. Designing the structurally simplified enediyne congeners retaining the impressive DNA cleaving properties is of great importance for potential use in chemotherapy or as tools for biotechnology. Ongoing research concerned with the development of bioactive enediyne mimics has required large quantities of acyclic enediynes. We initiated the research for the convenient and practical synthesis of of the open chain enediyne derivatives by simple elimination of tert-hydroxy group. By using above method, we synthesized several model enediynes which produce biradical species via enyne-allene intermediates. One of them is the model compounds which produce biradicals under acidic conditions, and the other is the enediynes which produce biradicals by ester-hydrolysis. Both model compounds produced carbon biradicals by their characteristic cascade reactions initiated by triggering devices. On the way of these investigations, we found that the biradicals transformed into zwitterionic species, and this reaction mechanisms were investigated. On the other hand, the acyclic enediyne possessing an aminomethyl group was designed and synthesized as a potential substrate for pyridoxal-dependent enzymes. This compound was shown to give cycloaromatized products by the reaction with pyridoxal or isonicotinaldehyde via the toluene biradical intermediate.