Synthesis of the manumycin family of antibiotics and novel ras farnesyl transferase inhibitors for cancer chemotherapy

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Project objective

Inhibitors of the Ras farnesyl transferase (FTPase) enzyme have recently been shown to possess great potential as anti-cancer agents, particularly for colon and pancreatic carcinomas. Members of the manumycin family of aminoepoxycyclohexenone antibiotics act as potent and selective inhibitors of FTPase but these complex natural products seem to be too inaccessible and unstable to be useful chemotherapeutic agents. However, there is good evidence that synthetic aminoepoxycyclohexenones could be designed with the necessary stability and accessibility, while retaining the desirable biological properties. No synthetic approaches to manumycin analogues have been reported but preliminary studies in York have developed suitable methodology. The overall aim of this proposal is to extend this chemistry, and to develop chiral modifications, in order to prepare the natural products, and simplified analogues, for biological screening. Novel chemistry includes organometallic coupling reactions, the use of chiral acetals and Lewvis acids, and the stereocontrolled synthesis of complex polyenes.

Original text from CORDIS.

Participants

• UNIVERSITY OF YORK · YORKCoordinatorUnited Kingdom
• Not availableCity levelFrance

Links

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