Solid Phase Synthesis Of Quinaldopeptin And Analogues

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Antitumour antibiotics have formed the basis of numerous agents used in the clinic for the treatment of cancer. The compounds may be used directly, such as paclitaxel or vincristine, or as the basis for the design of analogues, much as mitoxantrone is derived from studies of the anthracycline antibiotics. Quinaldopeptin is a cyclic peptide with potent antitumour activity that has not been thoroughly investigated since its isolation. It is the simplest member of a family of compounds that includes sandramycin, the luzopeptins and quinoxapeptins, which have been shown to have both antitumour and antiviral activity. We have used solid phase methods to synthesise other cyclic antitumour antibiotics and in this project we intend to apply these methods to the synthesis of quinaldopeptin and analogues. Initial solution phase synthesis to generate large amounts of the natural product, will be followed by a solid phase synthesis on oxime-resin that is convenient and will facilitate the synthesis of analogues using multipin technologies. Such an approach will allow the rapid assessment of the potential of quinaldopeptin as a lead compound for the development of agents with therapeutic potential in the treatment of cancer and other diseases.