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Asymmetric Construction of New Chiral Building Blocks and these Application to the Syntheses of Natural Products

新型手性结构单元的不对称构建及其在天然产物合成中的应用

基本信息

批准号：
01571146
负责人：
HIRAI Yoshiro
金额：
$ 1.15万
依托单位：
Toyama Medical and Pharmaceutical University Faculty of Pharmaceutical Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

An asymmetric construction of a common building block for the synthesis of several biologically active natural products offer the powerful methods for the synthesis of the desired natural products. Then, I have done the design of common building blocks for several alkaloids and an asymmetric construction of these building blocks. Furthermore, the conversion of these chiral building blocks to several alkaloids was carried out as follows.1) An asymmetric construction of a piperidine and a pyrrolidone and these application to the alkaloids synthesis Treatment of an acyclic compound with (R)-1-phenylethylamine in THF under the kinetic conditions gave the 3, 4-functionalized piperidine derivative in 90% ee (80% yield). When (S)-1-phenylethyamine was used, the its enantiomer was obtained in similar ee. Recrystallization of the piperidines hydrobromide increased the ee up to 98%. These optically active piperidine derivatives were converted stereoselectively to (-)-ajmalicine, (-)-tetrahydroーalstonine, and (+)-yohimbine. The 3, 4-functionalized pyrolidone derivative also was synshesized in about 60% ee (80% yield) by the same procedure as described above. This pyrrolidone is a versatile chiral building block for the synthesis of strychnine alkaloids.2) An asymmetric construction of pyrrolidines via the Sharpless asymmetric epoxidation A3-Hydroxy-2-functionalized Pyrrolidine derivative was prepared in 90% ee by utilizing the Sharpless epoxidation of the intermediate allyl alcohol starting from propargyl alcohol. A 3-Hydroxyー2,5-functionalized pyrrolidine derivative also was prepared through the Sharpless asymmetric epoxidation, a preparation of oxazoline ring system, and an intramolecular palladium-assist amino cyclization. These optically active pyrrolidines obtained were versatile chiral building blocks for the syntheses of pyrrolizidine alkaloids and carbapenems.

合成几种生物活性天然产物的共同构建块的不对称结构为合成所需的天然产物提供了强大的方法。然后，我做了几种生物碱的常见构建块的设计和这些构建块的不对称结构。此外，这些手性构件转化为几种生物碱的方法如下。1)不对称构造了哌啶和吡咯烷酮并将其应用于生物碱的合成。在动力学条件下，将一种无环化合物与(R)-1-苯乙胺在四氢呋喃中反应得到3,4功能化的哌啶衍生物，收率90%（收率80%）。当使用(S)-1-苯乙胺时，其对映体在类似的ee中得到。氢溴化哌啶的重结晶可使ee提高98%。这些具有光学活性的哌啶衍生物被立体选择性地转化为(-)-ajmalicine, (-)-tetrahydro alstonine和(+)-育亨宾。3,4功能化的pyroli酮衍生物也以60%的ee（80%的产率）通过上述相同的步骤合成。这种吡咯烷酮是合成士的宁生物碱的一种多功能手性构建块。2)以丙炔醇为起始原料，以Sharpless环氧化中间体烯丙醇为原料，在90% ee的条件下制备了不对称环氧化a3 -羟基-2功能化吡咯烷衍生物。通过Sharpless不对称环氧化反应、恶唑啉环体系的制备和分子内钯辅助氨基环化反应制备了3-羟基2,5功能化吡咯烷衍生物。得到的旋光性吡咯烷类化合物是合成吡咯烷类生物碱和碳青霉烯类化合物的多用途手性组成部分。