KIB OpenIR  > 昆明植物所硕博研究生毕业学位论文
脂肪族酯的选择性还原及新肉球菌素类似物的合成研究
Alternative TitleStudy of Chemoselective Reduction of Aliphatic Esters and Synthesis of Neoengleromycin Analogs
吕晓洁
Subtype硕士
Thesis Advisor朱华结
2007-06-06
Degree Grantor中国科学院昆明植物研究所
Place of Conferral昆明植物研究所
Degree Discipline药物化学
Keyword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
Abstract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。
Other AbstractStructurally 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.
Pages116
Language中文
Document Type学位论文
Identifierhttp://ir.kib.ac.cn/handle/151853/226
Collection昆明植物所硕博研究生毕业学位论文
Recommended Citation
GB/T 7714
吕晓洁. 脂肪族酯的选择性还原及新肉球菌素类似物的合成研究[D]. 昆明植物研究所. 中国科学院昆明植物研究所,2007.
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