中国科学院昆明植物研究所机构知识库
Advanced  
KIB OpenIR  > 昆明植物所硕博研究生毕业学位论文  > 学位论文
题名: 脂肪族酯的选择性还原及新肉球菌素类似物的合成研究
作者: 吕晓洁
学位类别: 硕士
答辩日期: 2007-06-06
授予单位: 中国科学院昆明植物研究所
授予地点: 昆明植物研究所
导师: 朱华结
关键词: 脂肪族酯 ; NaBH4 ; 选择性还原反应 ; 新肉球菌素 ; 异羟肟酸 ; 合成 ; 抗肿瘤活性
学位专业: 药物化学
中文摘要: 结构复杂的天然产物中常常含有多个酯基,选择性还原其中一个酯基是天然产物结构修饰经常遇到的问题。在论文前半部分把不同烷基取代的酯作为模型,对其进行了NaBH4还原研究。 新肉球菌素 (Neoengleromycin),是从中国特有真菌肉球菌 (Engleromyces goetzii) 中分离得到的一个含有异羟肟酸 (Hydroxamic acid) 结构的化合物,异羟肟酸化合物多数具有很好的生物活性。论文后半部分的内容是以L-谷氨酸 (L-Glutamic acid) 为原料合成了新肉球菌素异羟肟酸的类似物。 第一章综述主要由两部分组成。首先综述了NaBH4的研究进展,主要叙述NaBH4对于还原羰基化合物特别是选择性还原羰基的研究进展;其次对含有异羟肟酸结构的化合物的概况进行了介绍,对天然存在的异羟肟酸化合物和异羟肟酸化合物的合成做了综述。 第二章介绍了脂肪族酯的化学选择性还原。把不同烷基取代的酯作为模型,对其进行了NaBH4还原研究,测定了不同酯的起始反应温度,半衰期并计算了其活化能,用B3LYP/6-31++G(d,p)//HF/6-31G(d,p) 方法计算过渡态能量。不同取代基酯的起始反应温度表现出了比较明显的差别,表现出了一定的选择性,半衰期所显示出的反应活性与起始反应温度所显示的基本一致;取代基对于反应活性的影响验证了本课题组提出的奇偶碳效应。 第三章介绍了新肉球菌素类似物的合成。以L-谷氨酸为原料合成新肉球菌素的类似物,得到21个不同取代基的化合物。对其中8个化合物进行了体外抗肿瘤活性测试,发现化合物30,34和36对来源于淋巴瘤的淋巴样细胞Raji有较好的抑制活性,半数抑制浓度 (The 50% Inhibitory Concentration, IC50) 值分别为0.48、0.81和0.63 g/mL。化合物34同时还具有较好的人白血病细胞HL-60的抑制活性,IC50值为13.91 g/mL。研究了羟胺N上取代基对化合物抑制Raji活性的影响,发现取代基体积大的化合物比体积小的化合物抑制活性高,取代基的供电子效应也和抑制活性有关。
英文摘要: Structurally complex natural products often have two or more ester groups with slightly different reduction reactivities, and selective reduce one of them would be valuable. First part of the thesis describes the study of chemoselective NaBH4 reduction of aliphatic esters. Neoengleromycin, isolated from the fruiting bodies of the ascomycete Engleromyces goetzii, which was only found in China, was regarded as “hot off the press” by Nature Products Report in 2002. Neoengleromycin is composed of two aliphatic chains and a hydroxamic acid group which is well known of good biologic activities. In the second part of this thesis, synthesis of neoengleromycin analogs using L-glutamic acid is investigated. Research advance of chemoselective NaBH4 reduction of carbonyl group and products with hydroxamic acid group are reviewed in chapter 1. In chapter 2, esters with different alkyl substituents are used as the models used in the reductions with sodium borohydride, on-set temperatures, half-life periods and transition state (TS) energies were obtained experimentally. In addition, some of the TS energetics were computed using B3LYP/6-31++G(d,p)//HF/6-31G(d,p) method. The differences of on-set temperatures among these esters are substantial and some observed selectivities are obtained when the aliphatic substituents change from Me, Et, n-Pr to n-Bu. Odd-even carbon effect named in this study was observed. In chapter 3, syntheses of neoengleromycin analogs using L-glutamic acid are described. 21 compounds with different substituents were obtained of which 8 compounds were tested for in vitro antitumor activity. Compound 30, 34 and 36 possess moderate inhibit Raji cell activity with IC50 values of 0.48, 0.81 and 0.63 g/mL. Compound 34 also possesses moderate inhibit HL-60 activity with IC50 value of 13.91 g/mL. The steric hindrance of substituent on N of hydroxamic acid group and electrophobic effect relate on the inhibit Raji cell activity.
语种: 中文
内容类型: 学位论文
URI标识: http://ir.kib.ac.cn/handle/151853/226
Appears in Collections:昆明植物所硕博研究生毕业学位论文_学位论文

Files in This Item:
File Name/ File Size Content Type Version Access License
10001_200428010642002吕晓洁_paper.pdf(1286KB)----限制开放-- 联系获取全文

Recommended Citation:
脂肪族酯的选择性还原及新肉球菌素类似物的合成研究.吕晓洁[d].中国科学院昆明植物研究所,2007.20-25
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[吕晓洁]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[吕晓洁]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  中国科学院昆明植物研究所 - Feedback
Powered by CSpace