ACYCLIC DIASTEREOSELECTION--METHODOLOGY AND SYNTHESIS

描述：建议继续对以下领域进行调查 非环非对映选择性合成，重点是巴豆基金属化 反应和片段组装Aldol反应 天然产物合成。具体目标是：1.发展新能源 抗、抗二丙酸酯的合成方法学。这个 (Z)-巴豆基三氟硅烷36与b-羟基醛的反应 (Z)-巴豆基硅环丁烷112-114将被开发用于合成 抗，抗二丙酸酯，它们很难用其他方法合成 方法：研究方法。2.甲基酮-羟醛反应的立体化学研究 (I)甲基酮中的船状过渡态 羟醛反应将通过使用2H标记的烯醇硅烷122来探测 作为锂、硼和钛烯醇酸盐的前体。(Ii)综合报告 的C(13)-C(25)节段中，将使用 重点是125和126的Aldol反应。这些数据来自于 这项研究将补充在鲁他霉素系列中获得的结果，以及 应该会大大提高立体化学预测的能力 关于其他复杂片段连接的信息。3.新的分片方法 耦合。酒石酸戊基硼酸盐136e，z将被开发用于 醛的烯丙基硼化反应。得到的加合物137将是 阐述了手性甲基烯丙基硼酸酯138，然后与手性偶联 醛。预计138的非对映面选择性 会大到足以主宰大多数人的非立体面部偏好 醛。因此，这一方法应构成一项总体战略。 用于片段连接。4.Damavaricin的全合成完成 D.这一处于高级阶段的全合成将是 在下一个授权期内完成。一种针对生物的仿生策略 达马菌素C(天然衍生)合成链霉菌素C 也将被探索。5.完成一项完全合成 巴菲罗星A1。合成，它已经进展到了 大环85，将通过甲基的晚期Aldol反应完成 酮158和手性醛159。6.泰丹内酯的合成。这 该项目将提供对片段组装Aldol的更多了解 有问题。中间体二醛190的巴豆基硼化反应 通过E2反应区域选择性地引入三取代烯烃 在构象上灵活的系统也将被探索。

DESCRIPTION: It is proposed to continue investigations in the area of acyclic diastereoselective synthesis, with emphasis on crotylmetalation reactions and fragment assembly aldol reactions in the context of natural products synthesis. Specific goals are: 1. Development of New Methodology for the Synthesis of Anti, Anti Dipropionates. The reactions of b-hydroxy aldehydes with (Z)-crotyltrifluorosilane 36 and (Z)-crotylsilacyclobutanes 112-114 will be developed for the synthesis of anti, anti dipropionates, which are difficult to synthesize by other methods. 2. Stereochemical Studies of Methyl Ketone Aldol Reactions. (i) The involvement of boat-like transition states in methyl ketone aldol reactions will be probed by using the 2H-labeled enol silane 122 as precursor to lithium, boron and titanium enolates. (ii) A synthesis of the C(13)-C(25) segment of scytophycin C will be performed with emphasis on the aldol reaction of 125 and 126. The data that emerge from this study will complement results obtained in the rutamycin series, and should greatly increase the ability to make stereochemical predictions about other complex fragment couplings. 3. New Methodology for Fragment Coupling. Tartrate prenylboronates 136e,z will be developed for use in aldehyde allylboration reactions. The resulting adducts 137 will be elaborated to chiral methallylboronates 138 and then coupled with chiral aldehydes. It is expected that the diastereofacial selectivity of 138 will be large enough to dominate the diastereofacial preferences of most aldehydes. This methodology thus should constitute a general strategy for fragment coupling. 4. Completion of a Total Synthesis of Damavaricin D. This total synthesis, which is at an advanced stage, will be completed in the next grant period. A biomimetic strategy for the synthesis of streptovaricin C from damavaricin C (naturally derived) also will be explored. 5. Completion of a Total Synthesis of Bafilomycin A1. The synthesis, which has progressed to the stage of the macrocycle 85, will be completed by a late stage aldol reaction of methyl ketone 158 and chiral aldehyde 159. 6. Synthesis of Tedanolide. This project will give additional insight into the fragment assembly aldol problem. The crotylboration of meso dialdehyde 190 and the regioselective introduction of trisubstituted olefins via E2 reactions in conformationally flexible systems also will be explored.