Solid Phase Synthesis Of Quinaldopeptin And Analogues

喹啉及其类似物的固相合成

• 批准号: GR/T24463/02
• 负责人: Mark Searcey
• 金额: --
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=GR%2FT24463%2F02
• 关键词: Solid; Phase; Synthesis; Quinaldopeptin; Analogues

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.

抗肿瘤抗生素已经形成了临床上用于治疗癌症的许多药剂的基础。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。喹那多肽是一种具有强效抗肿瘤活性的环肽，自其分离以来尚未得到彻底研究。它是包括sandramycin、luzopeptins和quinoxapeptins的化合物家族中最简单的成员，这些化合物已被证明具有抗肿瘤和抗病毒活性。我们已经使用固相方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哪多肽及其类似物的合成。最初的溶液相合成以产生大量的天然产物，随后是肟树脂上的固相合成，这是方便的，并且将促进使用多针技术合成类似物。这种方法将允许快速评估喹哪多肽作为先导化合物用于开发在治疗癌症和其他疾病中具有治疗潜力的药剂的潜力。