ORGN 741 |
| Duocarmycins are an exceptionally potent class of antitumour antibiotics, which exert their activity through a sequence-selective alkylation of the N2 of adenine in the minor groove of DNA. The main drawback of these alkylating agents is their toxicity towards all proliferating cells. Therefore, the development of potent cytotoxic prodrugs which undergo cytochrome P450 (CYP)-mediated activation in the tumour, will lead to selective cell killing. The total synthesis of duocarmycin analogues will be described. The key step towards the total synthesis of these prodrugs is a free radical cyclisation in order to form the 5-membered ring attached to the indole (Figure 1). Results of the in vivo and in vitro cytotoxicity of the compounds prepared will be reported. Studies on new approaches towards the stereoselective total synthesis of the most potent duocarmycin prodrug derivative will be also presented.
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Total Synthesis, Materials, Molecular Recognition, Process R&D, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster
Division of Organic Chemistry |
