Total synthesis of Zoanthamine

佐安他明的全合成

• 批准号: 6837151
• 负责人: Fatima R Rivas
• 金额: $ 2.79万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6837151
• 关键词: Total; synthesis; Zoanthamine

18. GOALS FOR FELLOWSHIP TRAINING AND CAREER The primary goal for my training is to learn the necessary skills to become an excellent organic chemist who can teach organic chemistry at the university level and can conduct research independently. The Theodorakis' laboratory nurtures new ideas and encourages the development of new methodologies in organic synthesis. This approach will enhance my understanding chemical reactivity. The weekly research meetings of the Theodorakis' group during which every student presents a thorough explanation of their ongoing research will help me practice my teaching skills and to develop a better understanding of chemistry. In addition, the correlation between organic chemistry and biology is constantly discussed in order to better understand the biological mode of action of different molecules. This project will expose me to as much chemistry as needed to succeed in the laboratory as well as in the classroom. This fellowship would enable me to accomplish my career goals which are to complete my Ph. D to ultimately teach at the university level and set a role model to disadvantaged minority groups 19. NAME AND DEGREE(S) Emmanuel Theodorakis, 20. POSITION/RANK University of California, San 21. RESEARCH INTERESTS/AREAS Total Synthcsis of Natural Products and Drug Design 22. DESCRIPTION (Do not exceed space provided) SPONSOR Doctorate degree in Organic Chemistry Diego Organic Chemistry Professor i| _tl _;1 ",'ol"n -,,-Il_o]llo]-'_'i_l Our goal is to develop a feasible synthetic procedure that can yield Zoanthamine and other members of this alkaloid family such as norzoanthamine in a concise manner. Most of these alkaloids possess highly functionalized trans-decalone and heterocyclic aminal ring system along with at least three quaternary chiral centers (C-9, C-12, C-22 for zoanthamine). Zoanthamine and its relatives were found to inhibit phorbol myristate acetate induced inflammation in a model system. Norzoanthamine was found to inhibit the growth of P388 murine leukemia cell cultures. In addition, norzoanthamine inhibits IL-6 production. Recently, it has been reported that zoanthamine-type alkaloids suppress the decrease in bone weight. The construction of the core of zoanthamine will lead us to hopefully develop a library of its analogs to further study their potential as candidates for an osteoporotic drug and/or an anti-inflammatory drug. PHS 416-1 (Rev. 12/98) Form Page 2 BB co NAME(Last, first,middle initial) Individual NRSA Application Rivas, Fatima, R Tabte of Contents Page Numbers (Numberpagesconsecutively at thebottomthroughouthe applicationD. onotuse Section I-Applicant suffixesuchas5a, 5b.) Face Page (Items 1-8, 15), Form Page 2 (items 16-18, 22), and Table of Contents ========================================Section End===========================================

18. 奖学金培训和职业目标 我培训的主要目标是学习必要的技能，成为一名优秀的有机化学家，能够在大学教授有机化学并能够独立开展研究。 Theodorakis 实验室培育新思想并鼓励有机合成新方法的开发。这种方法将增强我对化学反应性的理解。 Theodorakis 小组每周举行的研究会议，每个学生都会对他们正在进行的研究进行全面的解释，这将帮助我练习我的教学技能并更好地理解化学。此外，有机化学与生物学之间的相关性不断被讨论，以便更好地理解不同分子的生物学作用模式。这个项目将使我接触到在实验室和课堂上取得成功所需的尽可能多的化学知识。这项奖学金将使我能够实现我的职业目标，即完成我的博士学位，最终在大学任教，并为弱势少数群体树立榜样 19. 姓名和学位 Emmanuel Theodorakis，20. 职位/级别加州大学圣何塞分校 21. 研究兴趣/领域 天然产物全合成和药物设计 22. 描述（不要超出所提供的空间） 赞助商 博士学位迭戈有机化学教授 | 有机化学博士_tl _;1 ",'ol"n -,,-Il_o]llo]-'_'i_l 我们的目标是开发一种可行的合成程序，可以以简洁的方式产生佐安他明和该生物碱家族的其他成员，例如去甲安他明。这些生物碱中的大多数具有高度功能化的反式十酮和杂环缩胺环系统以及至少三个季手性中心（对于花安他明来说是C-9、C-12、C-22）。在模型系统中，佐安他明及其相关化合物被发现可以抑制佛波醇肉豆蔻酸酯乙酸酯诱导的炎症。 Norzoanthamine 可抑制 P388 小鼠白血病细胞培养物的生长。此外，norzoanthamine 还可抑制 IL-6 的产生。最近，据报道，Zoanthamamine型生物碱可抑制骨重量的减少。佐安他明核心的构建将引导我们开发其类似物库，以进一步研究它们作为骨质疏松药物和/或抗炎药物候选者的潜力。 PHS 416-1（修订版 12/98）表格第 2 页 BB 公司姓名（姓氏、名字、中间名首字母） 个人 NRSA 申请 Rivas、Fatima、R 目录页码（整个申请过程中底部连续的页数 D.onotuse 第 I 部分 - 申请人后缀，例如 5a , 5b.) 正面页面（第 1-8、15 项）、表格页面2（第 16-18、22 项）和目录 ======================================== ====章节结束==============================================