Synthetic studies on Antitumor Antibiotic and Biological Activity

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I.Approaches to the total synthesis of manzamineA1. For the challenging construction of the complex hydroisoquinoline framework of manzamine A,we have been investigating a feasibility of the Diels-Alder reaction of suitably protected 3-alkyldihydropyridinones. Through an efficient intrmolecular D-A reaction of the dihydropyridinone and Danishefsky's diene, we have successfully constructed the central tetracyclic core of manzamine A.For the attainment of the more convergent synthetic route, it is preferable use the azocine-containing dienophile. For the preparation of this new dienophile as an optically active form, we investigated the two new synthetic route starting from L-serine derivative.2. According to the computer assisted conformational analysis of manzamine A and C,we have succeeded the synthesis of the natural manzamine C,its trans-isomer, and ring-modified analogs. All of the manzamine C analogs its trans-isomer showed similar in vitro cytotoxic activity to manzamine C itself.II.Approaches to the total synthesis of dynamicine AThe phenanthridine key intermediate for the total synthesis of dynamicin A,a potent antitumor antibiotic, has been synthesized by our synthetic methodology used for manzamine A synthesis.