合成研究癌症相關的RM2抗原

Abstract

前列腺癌是一種男生常被檢驗出來的癌症且 RM2 是一種多醣體的抗原，它會高度表現在前列腺癌症細胞表面上面，這種新型的抗原分別是屬於 ganglio-series 和 disialyl lacto-series type 1 chain 系列，且 RM2 抗原目前還沒有被人用化學方法所合成出來。 在本篇論文，我們試著用一鍋化的方法來合成RM2抗原，因此，我們先對 RM2 六醣進行逆合成分析，可以分解成單醣構築體、雙醣構築體、三醣構築體等三種醣的構築體，主要困難的地方是唾液酸和半乳糖以α(2->3)為主要鍵結所構成的構築體，目前還沒有用來當作一種構築體去進行一鍋化的反應，因為這三種構築體的活性會逐漸減少，我們在一個反應瓶裡面連續地反應去得到整個六醣體藉由一加二加三的一鍋化方法。 在我們的研究中發現，雙醣的構築體可以藉由磷酸唾液酸構築體 20 和半乳醣 14 所得到原本，我們想先用逐步地合成方法來測試一鍋化[1+2+3]策略是否能夠進行，但結果是很令人失望的，因此，[3+2+1] 的合成策略取代了原本的[1+2+3]一鍋化的方法，最後，我還是沒有合成出我所想要的六醣體，我藉由雙醣構築體 G 和三醣構築體 F 來合成出了五醣體 I，現在也正在著手於利用更有活性的捐供者來完成六醣體的全合成

Prostate cancer is the most commonly diagnosed cancer among men and the RM2 antigen has been discovered as a member of an antigenic carbohydrates family that is highly expressed on prostate cancer cells. The novel antigen RM2 belongs to ‘‘ganglio-series’’and the ‘‘disialyl lacto-series type chain’’ groups. And the RM2 antigen was not been synthesized by chemical method before. In this thesis, we tried to use one-pot strategy to synthesize the RM2 antigen. Therefore, hexasaccharide RM2 was retrosynthetically disconnected into three saccharide building blocks: Galactosamine building block, disaccharide building block, and sialyated trisaccharide building block. The difficult problem was that the sialic acid α(2,3) galactose was never used as a building block to do the one-pot synthesis before. Since the reactivities of these three building blocks decrease progressively, they can react sequentially in a single flask to construct the entire hexasaccharide in a single one-pot reaction by using a [1 + 2 + 3] approach. Here we reported the disaccharide building block was accomplished by phosphate sialoside 20 and galactose 14. Originally, we have done the step by step [1+2+3] strategy to test the one-pot synthesis strategy, but the result was disappointing. Therefore, the [3+2+1] strategy was displaced the previous [1+2+3] one-pot strategy. Overall, the hexasaccharide didn’t synthesize completely, only pentasaccharide I was accomplished by the disaccharide G donor and trisaccharide F acceptor. In the future, the more reactive donors 21 and 27 will be used to do the glycosylation with the acceptor I to accomplish the hexasaccharide.