第一部分: 含硼之胜肽衍生物合成與其生物活性評估 第二部分: 利用Passerini反應合成含硼之衍生物

(I) Synthesis and Biological Evaluation of Boron-Containing Peptide - Based Analogues (II) Synthesis of Passerini-type Boron-Containing Analogues

林家弘(Chia-Hung Lin)

指導教授 ： 潘伯申

淡江大學/理學院/化學學系碩士班/碩士(2012年)

https://doi.org/10.6846/TKU.2012.01347

摘要

第一部分:
本論文中我們設計與合成了兩系列含硼胜肽化合物。此類化合物可以以簡單的合成方法製備與純化。同時也使用了HepG2(肝癌)和MDA-MB231(乳癌)兩種癌細胞，來評估所合成之化合物的抗癌能力。藉由改變含硼化合物之結構來探討分子結構與生物活性之關係。
第二部分:
近年來由於含硼化合物在藥物開發上逐漸受到注意，因此含硼化合物的合成也逐漸受到重視。本研究利用Passerini三單元組成反應成功的合成出一系列的含硼化合物。由於多單元組成反應具備操作簡單、產物產出快速等優點，因此非常適合應用於含硼藥物的開發上。

關鍵字

含硼胜肽化合物 ； passerini多組成反應

並列摘要

part 1
In this project, we have designed and synthesized two series of boron-containing analogues. These analogueswere synthesized via facile and efficientsynthetic operations.
The anticancer potency of the synthesized boron-containing derivatives were evaluated by two cancer cell lines: HepG2 (liver cancer) and MDA-MB231 (drug resistant breast cancer). The structure-activity relationship (SAR) profiles indicated that inclusions of aphenylalanine in position 2, benzyl-protected serine in position 3, and a potassium trifluoroborate functional group greatly improved the compound’s ability against HepG2 and MDA-MB231 cell lines.

part 2
In recent years, boron-containing compounds havedrawn the attention of medicinal research communityafter the success of the FDA approved drug: Velcade. In the second project, we have utilized the Passerini-type 3components reaction (P3CR) to construct series of boron-containing derivatives. Although the reaction condition was not yet optimized, the result have shown the novel protocol of generating structurally diverse boron-containing analogues via multicomponent reaction.

並列關鍵字

boron-containing peptide analogues ； passerini multicompoent reaction

參考文獻

17. Yang, W.; Gao, S.; Gao, X.; Karnati, V. V. R.; Ni, W.; Wang, B.; Hooks, W. B.; Carson, J.; Weston, B. Bioorg. Med. Chem. Lett. 2002, 12, 2175-2177.

11. Soloway, A. H.; Tjarks, W.; Barnum, B. A.; Rong, F.-G.; Barth, R. F.; Codogni, I. M.; Wilson, G. Chem. Rev. 1998, 98, 1515–1562.

1. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483.

3. Ishihara, K.;Yamamoto, H. Eur. J. Org. Chem. 1999, 527-538.

4. Petasis, N.A.; Zavialov, I.A. J. Am. Chem. Soc. 1997, 119, 445-446.