Total Synthesis of Anti-Cancer Natural Products

抗癌天然产物的全合成

• 批准号: 7674771
• 负责人: PHIL S BARAN
• 金额: $ 63.05万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-07 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7674771
• 关键词: Alkaloids; Antihypertensive Agents; Arts; Biochemical Process; Biological; Biological Factors; Biology; Blood Platelets; Cancer Biology; Chemicals; Chemistry; Clinical; Collaborations; Complex; Development; Diterpenes; Family; Family member; Gynecologic; Light; Malignant Neoplasms; Marines; Medicine; Methodology; Methods; Nature; Pattern; Peptides; Pharmaceutical Preparations; Solutions; Source; TNF gene; abstracting; analog; cancer therapy; chemical synthesis; design; inhibitor/antagonist; innovation; leukemia; member; novel; tumor

This proposal aims at using chemical synthesis to prepare four classes of anticancer natural products with great potential that have eluded study due to their scarcity in nature and the fact that no solution for their chemical synthesis exists. Practical syntheses of vinigrol, maoecrystal, kapakahine, sarcodonin, and related family members will require the development of new synthetic methodologies, as well as the exploration of novel chemical entities and reactivity patterns. In addition, a thorough exploration of their biology through the synthesis of carefully designed analogs is planned. Each of these natural product families represent ideal targets from both a chemical and biological perspective. Chemically, they challenge the state of the art and require innovative solutions in order to accomplish their practical total synthesis. They elicit their biological influence through as yet unknown mechanisms and thus have the potential to shed light on fundamental biochemical processes. Finally, they are endowed with potent bioactivity and could conceivably enter into a clinical setting. New strategies and methods in chemistry and substantial contributions to medicine are anticipated through strategic collaborations with several leaders in the field of cancer biology.

该提案旨在利用化学合成方法制备四类具有巨大潜力的抗癌天然产物，这些天然产物由于自然界中的稀缺性以及不存在化学合成的解决方案而未能被研究。长春醇、maoecrystal、kapakahine、sarcodonin 和相关家族成员的实际合成将需要开发新的合成方法，以及探索新的化学实体和反应模式。此外，还计划通过合成精心设计的类似物来彻底探索它们的生物学特性。从化学和生物学的角度来看，这些天然产品家族中的每一个都代表了理想的目标。在化学方面，它们挑战了最先进的技术，需要创新的解决方案才能完成其实用的全合成。它们通过迄今未知的机制产生生物学影响，因此有可能揭示基本的生化过程。最后，它们被赋予了强大的生物活性，可以想象进入临床环境。通过与癌症生物学领域的几位领导者的战略合作，预计将在化学领域产生新的战略和方法，并对医学做出重大贡献。