Solid Phase Synthesis Of Quinaldopeptin And Analogues

抗肿瘤抗生素已成为临床上用于治疗癌症的众多药物的基础。这些化合物可以直接使用，如紫杉醇或长春新碱，或作为设计类似物的基础，就像米托蒽醌是从蒽环类抗生素的研究中衍生出来的一样。Quinaldopeptin是一种具有有效抗肿瘤活性的环肽，自其分离以来尚未被彻底研究。它是一个化合物家族中最简单的成员，该家族包括sandramycin， luzopeptin和quinoxapeptin，这些化合物已被证明具有抗肿瘤和抗病毒活性。我们已经使用固相法合成了其他环状抗肿瘤抗生素，在本项目中，我们打算将这些方法应用于喹多普汀及其类似物的合成。最初的固相合成产生大量的天然产物，随后将在肟树脂上进行固相合成，这是方便的，并且将有利于使用多针技术合成类似物。这种方法将使我们能够快速评估喹纳多普汀作为先导化合物的潜力，以开发在治疗癌症和其他疾病方面具有治疗潜力的药物。

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.