Synthesis of atypical carotenoids: self-preserving inhibitors of lipid peroxidati

描述(申请人提供)：项目摘要非典型类胡萝卜素的合成：自保的脂质过氧化抑制剂小分子安全有效地抑制脂质双层的过氧化，将大大推进许多流行的人类疾病的治疗，包括动脉粥样硬化、癌症、黄斑变性和关节炎。然而，已知的大多数O抗脂过氧化药物都有重要的局限性。例如，典型的类胡萝卜素，如O虾青素，具有很强的自我-羟基胡萝卜素倾向(1)-···典型的类胡萝卜素如O虾青素具有强烈的自我--自我--自我相比之下，有几个最近发现的Me Me OH“非典型”胡萝卜素具有潜在的Me通过Me O联黄素(2)自我保护的作用机制而具有特殊的抗脂过氧化活性。具体地说，该研究计划将开发高效灵活地合成HoO-Me非典型胡萝卜素Peridinin(1)、Ho-Me聚黄素(2)和二-[(6-O-油酰基-2-D-Ho-Me葡萄糖基)氧基]-虾青素(3)，对我进行系统的结构/功能研究，了解它们独特的抗脂过氧化OH谱，并通过合理指导的组合合成和di-[(6-O-oleoyl-！-D-glucopyranosyl)oxy]-astaxanthin(3)高通量筛选的迭代循环，广泛优化其Me-O-OH活性。PHS 398/2590(05/01版)页面续格式页面

DESCRIPTION (provided by applicant): Project Summary Synthesis of atypical carotenoids: self-preserving inhibitors of lipid peroxidation Small molecules that safely and effectively inhibit the peroxidation of lipid bilayers stand to substantially advance the treatment of many prevalent human diseases, including atherosclerosis, cancer, macular degeneration, and arthritis. However, most of the known O antilipoperoxidants have important limitations. Me Me O Me H HO Me For example, typical carotenoids such as O astaxanthin have a strong propensity for self- Me HO Me peridinin (1) Me OAc destructive interactions with reactive oxygen Me species, which limits the lifetime of the lipid O protective effect and leads to the generation of HO Me Me harmful carotenoid breakdown products. In contrast, there are several recently discovered Me Me Me Me OH "atypical" carotenoids that have the potential Me for exceptional antilipoperoxidant activities via Me O synechoxanthin (2) self-preserving mechanisms of action. Specifically, this research program will develop O highly efficient and flexible syntheses of the HO O O O Me atypical carotenoids peridinin (1), HO O Me synechoxanthin (2), and di-[(6-O-oleoyl-2-D- HO Me Me Me Me glucopyranosyl)oxy]-astaxanthin (3), execute Me Me Me Me systematic structure/function studies to Me O O OO OH understand their unique antilipoperoxidant OH profiles, and extensively optimize their Me O OH activities via iterative cycles of rationally- guided combinatorial synthesis and high- di-[(6-O-oleoyl-!-D-glucopyranosyl)oxy]-astaxanthin (3) throughput screening. PHS 398/2590 (Rev. 05/01) Page Continuation Format Page