论文总字数：13947字

摘 要

半抗原衍生物的半合成，抗微管蛋白化合物，描绘了生物活性所必需的一些分子特征。在本研究过程中，重新研究了rhazinicine的形成方法，并提出了新的机理。

Rhazinilam 是一种从Rhazya stricta ^【1】（Apocynaceae）中分离出来的物质，已在马来西亚植物Kopsia singapurensis Ridlay中以筛选作用于微管蛋白 - 微管平衡的植物提取物的框架重新分离。^【2】微管蛋白是参与细胞分裂期间有丝分裂纺锤体形成的普遍存在的蛋白质。秋水仙碱，长春花碱和紫杉醇是三类微管平衡抑制剂的主要代表。已经显示^{【3】【4】}可以认为，rhazinilam可以被认为是有丝分裂纺锤体毒素中的新的领导者，因为它具有长春花碱和紫杉醇类化合物的作用：它诱导微管蛋白的不可逆组装，称为螺旋化，抑制冷诱导的微管分解。

Rhazinilam与微管蛋白的相互作用发生在与秋水仙素所观察到的浓度相似的浓度下。然而，rhazinilam在微管蛋白上比长春花碱和紫杉醇活性较低。因此，我们对分子进行了简单的修改，目的是在微管分解测定中获得更强的活性。初步结构 - 活性细胞研究表明，两个芳环和内酰胺羰基是活性必需的基本特征。 我们在这里报告了rhazinilam的功能衍生物的合成和更详细的结构 - 活性研究的结果。

已经表明，rhazinilam是植物提取物的植物，其天然前体是5,21-二氢恶嗪啉^【5】。也可以从伐昔单铵^{【6】【7】}开始合成Rhazinilam。

本次研究提供了一种新型的合成rhazinicine的方法，通过七步得到我们的目标，合成通过偶联，还原，去保护等多个步骤，涉及了萃取，抽滤，旋蒸等基本操作。

关键词： 全合成 生物碱 动态动力学

Abstract

Semi-synthetic derivatives of semi-antigenic derivatives, anti-tubulin compounds, depict some of the molecular characteristics necessary for biological activity. In the course of this study, the formation of rhazinicine was re-examined and a new mechanism was proposed.

Rhazinilam is a substance isolated from Rhazya stricta ^[1] (Apocynaceae), which has been re-isolated in the framework of the Malaysian plant Kopsia singapurensis Ridlay to screen for plant extracts acting on tubulin-microtubules. [2] Tubulin is a ubiquitous protein involved in the formation of mitotic spindles during cell division. Colchicine, vinblastine and paclitaxel are the main representatives of the three types of microtubule balance inhibitors. It has been shown that ^{[3] [4]} it can be thought that rhazinilam can be thought of as a new leader in mitotic spindle toxins because it has the effect of vinblastine and paclitaxel compounds: it induces irreversible assembly of tubulin, For the spiraling, inhibition of cold induced microtubule decomposition.

The interaction of rhazinilam with tubulin occurs at a concentration similar to that observed for colchicine. However, rhazinilam has less activity on tubulin than vinca and paclitaxel. Therefore, we have made simple modifications to the molecule in order to achieve stronger activity in microtubule decomposition assays. The preliminary structure - active cell studies have shown that two aromatic and lactam carbonyl groups are essential for essential properties of activity. Here we report the synthesis of rhazinilam functional derivatives and the results of more detailed structural-activity studies.

It has been shown that rhazinilam is a plant extract of the plant whose natural precursor is 5,21-dihydrooxazoline ^[5]. It is also possible to synthesize Rhizilam from farneside ^{[6] [7]}.

This study provides a new method for the synthesis of rhazinicine, which is based on seven steps to get our goal. The synthesis is carried out by coupling, reducing and deprotecting. It involves the basic operation of extraction, extraction and steaming.

Key words: fully synthetic alkaloid dynamic kinetics

目录

摘要 2

Abstract 3

第一章 文献综述 1

1.1生物碱的介绍 1

1.2动态动力学拆分 2

1.3 催化不对称 2

1.4.1选择性铂介导的sp³ C-H插入/β-H消除;（-）- rhazinilam的总合成 4

1.4.3金属催化的C-H硼化/ Suzuki偶联反应和氧化环化; （±）-rhazinicine的全合成 7

第二章 实验部分 9

2.1 偶联缩合反应 9

2.2水解反应 10

2.3还原反应 10

第三章 实验结果与讨论 12

参考文献 14

致谢 15

第一章 文献综述

1.1生物碱的介绍

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