(I)含硼之胺基甲基化合物的合成與其生物活性評估 (II)含硼Passerini 化合物之合成與其生物活性評估

(I)Synthesis of Boron-containing Aminomethyl Analogues and their Biological Evaluation (II)Synthesis of novel Boron-containing Passerini Analogues and their Biological Evaluation

蔡志承(Chih-Cheng Chai)

指導教授 ： 潘伯申

淡江大學/理學院/化學學系碩士班/碩士(2013年)

https://doi.org/10.6846/TKU.2013.00249

摘要

近幾年在藥物合成上，不再侷限於一般天然物中含有的元素。硼，亦
被使用在藥物合成中，雖然其藥用機理尚未被完整地建立，但因在生物活
性上有高度選擇性及高度活性，所以依然有很多化學家投入研究。本論文
分為兩個部分，合成不同類型的含硼化合物。
第一部分:
將含硼起始物與胺基酸合成，並進行還原，藉此得到具有aminomethyl
結構的化合物，而此類結構常見於天然物中，在藥物中亦可見到，故合成
出含硼的aminomethyl 化合物。使用HepG2(肝癌),MDA-MB231(乳癌)和
A549(肺癌)三種癌細胞，來評估所合成之化合物的抗癌能力。

第二部分:
Passerini reaction 為三個單元組成之反應，用含硼之酸或醛作為起始
物，於微波反應槽內反應，合成出α-acyloxyl amides 的化合物
(A1-A20,B1-B10)。此此方式進行合成，其操作簡單，且大量縮短反應時間。
另外只需以水做為反應溶劑，不需添加任何路易士酸進行催化，而在純化
上亦只需再沉澱即可得到乾淨的產物，達到綠色化學之裡想。
而後將所得之化合物進行一系列的藥物化學結構與活性關係，找出作
為後續藥物開發的領導藥物。

關鍵字

含硼胜肽化合物 ； passerini多組成反應

並列摘要

Part 1
Six of peptidyl boron-containing analogs were designed and successfully synthesized. Their anti-proliferative activities against hepatocellular carcinoma cells (HepG2) and human metastatic breast cancer cells (MDA-MB231) were evaluated by MTT assay. Unfortunately, none of the synthesized analogs were found active against the cancer cell lines. More analogs are being synthesized and the result will be reported in due course.

Part 2
In this report, a Passerini three-component reaction with a boron- containing carboxylic acid or a boron-containing aldehyde in water under microwave irradiation was developed. This methodology allows an efficient formation of a broad range of boron-containing a-acyloxy amides under mild condition in short reaction times. Two series of boron-containing a-acyloxy amides were synthesized and screened by MTT assay, and two potential lead compounds were found to be potent against HepG2 cancer cell.

並列關鍵字

boronic ester ； Multicomponent reactions ； Passerini reaction ； anti-cancer ； HepG2

參考文獻

5. Yu, H., Wang, B. Synthetic Communications 2001, 31, 2719.

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

11. Liebeskind, L. S., Srogl, J. J. Am. Chem. Soc. 2000, 122, 11260-11261.

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

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