Systematic Synthetic Stuchies on Bioactive Alkaloids and Their Biokeical Activiiies

许多生物碱在自然界中大量存在，并显示出有趣的药理活性。由于麋鹿滑块的数量有限，因此制备这些化合物以研究它们的生物学性质是非常重要的。本研究的目的是系统构建这些化合物并研究其作用机制。最近，Ramo和m-workers从信州大学的非洲豆科植物中分离到一种特殊的胺A，并鉴定为(+)-iso6-cassine的苯甲酰衍生物。合成谱胺A的关键反应是pd催化立体选择性环化生成2,6-环哌啶环。当Pd。以^2(dba)^3为催化剂，以Cbm为保护基团，trail/cis的比值为79/21。谱胺A的全合成正在进行中。以C12Pd(CH3CN)2催化的烯丙基酯非对映选择性环化为关键步骤，实现了吡喃嘧啶的合成。该化合物对线粒体NADH-uhiquioone氧化还原酶（复合体I）的抑制活性略低于顺式solamin等普通单thf醋酸原素。在本研究的过程中，还实现了图克林的绝对构型的合成和测定。

A number of alkaloids have been burl abundantly in nature and marry of than show interesting pharmalogical adivitites. Due to the amount of elk: slide is limited from the native, it is very important to prepare these compounds in order to study their binlogical properties. The aim of this study is to construct these compounds systenatically and solve the mechanism of action.1. Synthetic studies on spectamine ARecentlty spectiamine A was isolated by Ramo and m-workers at Shinshu Univemity icon African legume, (Is s i a apectahilis and identified as °Obenzoyl derivative of (+)-iso6-cassine. The key reaction of the synthesis of spectamine A is Pd-catayzed stereceelective cyclization to afford 2,6-traos-piperidine ring. When Pd.^2(dba)^3 was used as a catalyst and Cbm was used as a protecting group, the ratio of trail/cis was 79/21. The total synthesis of spectamine A is currently under way.2. Synthess of pyranicynTotal synthesis of pyranicin was achieved using C12Pd(CH3CN)2-catalyzed diastereoselective cyclization of the allyfic ester as the key step. The inhibitory activity of this compound for mitochiondrial NADH-uhiquioone oxidoreductase (complex I) was slightly poorer than that of ordinary mono-THF acetogenins such as cis-solamin. In the course of this study synthesis and determination of the absolute configuration of tookinelin was aka achieved.