| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
To understand the usefulness of diketopiperazine (DKP) template as a bio-function-mimicking molecular platform in medicinal chemistry, in this research project, we planed to establish a convenient synthetic method for DKP and develop a new anticancer agent based on the DKP structure. As results, 1) a new convenient synthetic procedure for monodehydro-DKP derivatives which has a dehydro-structure at anα,β-position of the DKP ring. 2) this method was successfully applied to the synthesis of a chiral derivative of naturally occurring anticancer agent, phenylahistin. 3) a structural optimization of DKP was carried out to obtain a highly potent anticancer derivative, and a derivative which is not only potent but also stable against cytochrome P450 metabolism was developed. 4) Additionally, in an anticancer drug, a water-soluble prodrug for highly insoluble anti-microtubule agent was also developed, and 5) New efficient solid-supported chiral auxiliary for the preparation of chiral amino acids, which are needed for diketopiperazine synthesis as starting materials, was developed.
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