2 + 3 ANNULATION PROTOCOL--NATURAL PRODUCT SYNTHESIS

这项建议涉及我们继续努力，以期 温和、立体控制和对映体选择性方法学的发展 五元环化合物的结构。这项技术有它的优点 最终目标环导致环戊烯、二氢呋喃和 吡咯啉，因为它们构成了许多天然产物的亚单位 生物学意义。它是基于[2+3]分子间的 将二烯酸酯阴离子加到羰基衍生物中(用于 环戊烯和二氢呋喃)或[4+1]分子内加成 叠氮化物为二烯(用于吡咯烷)。最重要的发展 在这个项目中将解决的是对废止的详细调查 烯酮和醛的组成，其中二烯酸酯来源于4- 硅氧基溴代巴豆酸盐。硅介导的重排反应 乙烯基环丙烷和乙烯基氧烷合成环戊烯和二氢呋喃 有可能提供最温和的环扎程序来 约会。 该项目将遵循以下主要目标：a.发展 取代开环的亲核或自由基替代品的 乙烯基环丙烷和乙烯基氧烷。B.详细调查 2-二烯酸根阴离子加成反应的立体化学过程 溴代巴豆苷转化为醛和烯酮，以了解 这一过程的非对映选择性。C.调查氟化物-- 硅烯醇醚端基乙烯基环丙烷的催化重排反应 和乙烯基环氧烷，以及对这一过程的机械细节的洞察。 D.对映体选择性合成聚氧环氧乙烷和 通过手性-辅助法(试剂控制)合成乙烯基环丙烷 或通过向手性前体(底物)添加上述二烯醇酸盐 控制)。E.研究从刚性到手性转移的可能性 手性硅助剂。F.将这些方法应用于 拒食性物质--刺五加素、吡咯里西定和 已知的抗生素或抗病毒活性的吲哚利定生物碱，以及 呋喃亚基是许多抗生素的组成部分； 香叶酸的第二代合成。研究方向 下一个资助期的目的是结束调查 为了使[2+3]不对称环化是必要的 方法学是碳环和杂环领域的永久工具 综合。可靠地提供环戊烷、呋喃和吡咯烷 Units将这种方法的应用扩展到 具有生物学意义的杂环天然产物。

This proposal addresses the continuation of our efforts aimed at the development of mild, stereocontrolled, and enantioselective methodology for the construction of five-membered-ring compounds. The technique has as its ultimate goal annulations leading to cyclopentenes, dihydrofurans, and pyrrolines, as these constitute subunits of many natural products of biological significance. It is based on either the [2+3] intermolecular addition of ester dienolate anions to carbonyl derivatives (for cyclopentenes and dihydrofurans) or the [4+1] intramolecular addition of azides to dienes (for pyrrolines). The most important development addressed in this project will be the detailed investigation of annulations of enones and aldehydes with the dienolate derived from 4- silyloxybromocrotonate. The silicon-mediated rearrangements of vinylcyclopropanes and vinyloxiranes to cyclopentenes and dihydrofurans hold the potential of providing on of the mildest annulation procedures to date. The project will be guided along the following major aims: a. Development of nucleophilic or radical alternatives to the ring opening of vinylcyclopropanes and vinyloxiranes. b. Detailed investigation of the stereochemical course of the additions of dienolate anions derived from 2- bromocrotonates to aldehydes and enones in order to understand the diastereoselectivity of this process. c. Investigation of fluoride- catalyzed rearrangements of silyl-enol-ether-terminated vinyl-cyclopropanes and vinyl-oxiranes and insight into mechanistic details of this process. d. Investigations of enantioselective synthesis of vinyloxiranes and vinylcyclopropanes either by a chiral-auxillary approach (reagent control or by additions of the above dienolates to chiral precursors (substrate control). e. Investigation of possible chirality transfer from rigid chiral silicon auxiliaries. f. Applications of these methodologies to the preparation of specionin (an antifeedant substance), pyrrolizidine and indolizidine alkaloids of known antibiotic or antiviral activities, and the furanoid subunits that are integral parts of many antibiotics; and to the second generation synthesis of retigeranic acid. The direction of research during the next funding period is aimed at the conclusion of investigations that are necessary in order to render the [2+3] asymmetric annulation methodology a permanent tool in the field of carbocylic and heterocylic synthesis. Reliable provision of cyclopentanoid, furanoid, and pyrroline units extends the applications of this methodology to the design of heterocyclic natural products of biological significance.