SYNTHESIS OF POLYHDROXYLATED NATURAL PRODUCTS

描述：(主要调查人员摘要)这项工作的具体目标 修订后的竞争续约申请如下：(1)新方法 四氢呋喃合成。我们将进一步发展(3+2)反应。 生成一般结构98和114的羰基化合物和烯丙基硅烷 通过第二醛与环氧乙烷的不对称烯丙基硼反应 伽马-硅基叶酸硼酸盐或伽马-硅基叶基硼烷97、101、112和113。这 方法论有可能成为一种极其普遍和高度 立体选择性三组分偶联法合成取代基团 四氢呋喃。(2)(3+2)环流策略的综合应用 用于四氢呋喃的合成。醛和醛的(3+2)环化反应 官能化的烯丙基硅烷将应用于布拉特星的合成， Asimicin和三杆菌蛋白，为番荔枝乙酸根素家族成员。 将进一步扩展(3+2)方法 与果胶毒素的合成II.(3)当归B的合成 将专注于开发立体控制合成的方法 手性联芳基单元以及烯丙基硅烷(3+2)的进一步延伸 四氢呋喃合成的环化策略，特别是 手性环己烯基硅烷197用于合成关键的三环烯酮162。这个 安格米星B的合成也为进一步探索 我们的2-碘-糖基供体方法合成2-脱氧糖苷。(4) 金黄色抗生素的第二代合成：米曲霉素。我们会 二代合成米曲霉素的研究进展 色霉酮，天然的苷元。这一综合将说明 2-碘和2-溴糖基供体方法学的合成潜力，以及 定义半合成类似物合成的有效策略 修饰的低聚糖单元。(5)金黄色类似物的合成。 结构简化的类似物251、252、253和/或254将被合成为 确定最大DNA结合和抗肿瘤的结构要求 活动。

DESCRIPTION: (Principal Investigator's Abstract) The specific aims of this revised competitive renewal application are: (1) New methodology for Tetrahydrofuran Synthesis. We will further develop the (3+2) reactions of carbonyl compounds and allylsilanes of general structure 98 and 114, generated by the asymmetric allylboration reactions of a second aldehyde with the gamma-silylalylboronates or gamma-sily1alylboranes 97, 101, 112 and 113. This methodology has the potential to become an extremely general and highly stereoselective three component coupling method for synthesis of substituted tetrahydrofurans. (2) Synthetic Applications of the (3+2) Annulation Strategy for Tetrahydrofuran Synthesis. The (3+2) annulation reactions of aldehydes and functionalized allylsilanes will be applied to the synthesis of bullatacin, asimicin, and trilobacin, members of the Annonaceotus acetogenin family. Further extensions of the (3+2) methodology will be developed in connection with a synthesis of pectenotoxin II. (3) Synthesis of Angelmicin B. This work will focus on development of methods for stereocontrolled synthesis of the chiral biaryl unit, as well as further extensions of the allylsilane (3+2) annulation strategy for tetrahydrofuran synthesis, specifically use of the chiral cyclohexenylsilane 197 for synthesis of the key tricyclic enone 162. The angelmicin B synthesis also presents the opportunity for further exploration of our 2-iodo-glycosyl donor methodology for synthesis of 2-deoxyglycosides. (4) Second Generation Synthesis of Aureolic Acid Antibiotics: Mithramycin. We will develop a second generation synthesis of mithramycin starting from chromomycinone, the natural aglycone. This synthesis will illustrate the synthetic potential of the 2-iodo and 2-bromo glycosyl donor methodology, and define an efficient strategy for synthesis of semi-synthetic analogs with modified oligosaccharide units. (5) Synthesis of Aureolic Acid Analogs. Structurally simplified analogs 251, 252, 253 and/or 254 will be synthesized to define the structural requirements for maximal DNA binding and antitumor activity.