General Methods for Synthesis of Bioactive Materials

超出所提供的空间。在这个应用中提出的研究的统一思路是发展立体和对映体控制的方法来构建全碳季碳中心。尽管在这一领域取得了显著的进展，但手性全碳季中心的构建仍然是化学合成或修饰许多具有生物学意义的分子的主要障碍。我们提出的研究将进一步定义两种强大的方法的实用性，这两种方法是我们率先用于组装含有四元碳中心的复杂骨架的：分子内Heck插入和前手性烯醇化物与手性sp 3亲电试剂的烷基化。含有多个吡咯烷喹啉亚基的复杂生物碱是我们提出的全合成努力的主要焦点。我们的目标是开发一般的方法和合成策略，这将首次允许通过化学合成在有意义的范围内获得这种大型吲哚生物碱家族的药理重要成员。多吲哚类生物碱的总合成靶标包括霍奇金碱、异精子碱、四叉胺A、C和H、communesin A和11,11′-二脱氧维拉西林。其他的全合成靶点有长春碱和长春碱相关生物碱文库，以及复杂的松香内酯瓦巴因、strophanthidin和smentosigenin a。我们还将合作研究多吲哚类生物碱镇痛活性的结构基础，并评价代表性多吲哚类生物碱的抗感染和抗肿瘤特性。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. The unifying thread of the research proposed in this application is the development of stereo- and enantiocontrolled methods for constructing all-carbon quaternary carbon centers. Although notable progress has been achieved in this area, the construction of chiral, all-carbon quaternary centers remains a major hurdle for chemical synthesis, or modification, of numerous biologically significant molecules. The proposed studies will further define the utility of two powerful methods that we have pioneered for assembling complex skeleta containing quaternary carbon centers: intramolecular Heck insertions and alkylations of prochiral enolates with chiral sp 3 electrophiles. Complex alkaloids that contain multiple pyrrolidinoindoline subunits are a major focus of our proposed total synthesis endeavors. Our aim here is to develop general methods and synthesis strategies that, for the first time, will allow pharmacologically significant members of this large indole alkaloid family to be accessed on meaningful scales by chemical synthesis. Polyindoline alkaloid total synthesis targets include hodgkinsine, idiospermuline, quadrigemines A, C and H, communesin A, and 11,11'- dideoxyverticillin. Other total synthesis targets are vincorine and vincorine-related alkaloid libraries and the complex cardenolides ouabain, strophanthidin and sarmentosigenin A. We will also collaborate in studies to define the structural basis of the analgesic activity of polyindoline alkaloids and evaluate the antiinfective and antitumor properties of representative polyindoline alkaloids. PERFORMANCE SITE ========================================Section End===========================================