Rollicosin 及其衍生物之合成研究

Synthetic Approaches to Rollicosin and its Analogs

王坤生(kun-shen wung)

指導教授 ： 吳明忠

高雄醫學大學/生命科學院/醫藥暨應用化學研究所/碩士(2004年)

摘要

Rollicosin 6, 是由Rollinia mucosa Bill 分離出來，由於其對腫瘤細胞展現了優越的活性，因此我們針對其具有4-S 組態和4位置無OH基之類似物進行合成之探討。
首先,類似物7之合成是藉由一Pd催化之反應將9a與10偶合,化合物9a之合成是由4-pentyn-1-ol 開始,經由TMS保護,PCC氧化,溴鎂乙烯加成,Claisen 重排,不對稱双醇化,去矽烷化反應,其總產率為8%。化合物10是由双碘化合物11跟內酯化合物12進行烷化反應而來。而双碘化合物11之合成,是由5-hexen-1-ol開始,經由保護醇基,碘化反應,去矽烷反應,甲苯磺醯化反應,最後進行碘化反應,其總產率為28%。接著化合物10與化合物9進行偶合反應可得化合物35,再經氫化,m-CPBA氧化及熱脫去反應即可得到化合物7。
化合物8之合成設計主要是17經開環加成反應再經由氫化炔基。為了測試此一合成策略,我們即以17為目標進行合成探討，而化合物17之製備是由20與15進行烷化反應,再經氧化及熱脫去反應可得,而後續之步驟尚在研究之中

關鍵字

乙醯化合物

並列摘要

Rollicosin 6, isolated from Rollina mucosa Bill, exhibited remarkable cytotoxicity against human cancer cell line. In this thesis, a 4-deoxy rollicosin analog and 4-S rollicosin were designed and synthesized.
The synthesis of compound 7 was based on a palladium catalyzed coupling of lactone 9a and vinyliodide 10. The synthesis of compound 9a was started from 4-pentyn-1-ol in six steps, including protection of the terminal acetylene, oxidation of the alcohol, vinylmagnesium bromide addition to the aldehyde, ortho-ester claisen rearrangement to give the ??, ??-unsatured ester. Followed by the asymmetric dihydroxylation and desilylation.gave 9a in 8% overall yield. Compound 10 was prepared by alkylation of diiodide 11 with lactone 12. The diiodide 11 was prepared in five steps, including protection of the alcohol, hydrostannylation of the terminal acetylene, desilylation, tosylation of the alcohol and iondiation. The overall yield is 28%. Eneyne 35 was produced by coupling of 9a and 10 . Hydrogenation of 35 using rhodium as a catalyst gave 36. Finally, compound 7 was obtained by oxidation of 36 with m-CPBA and followed by therminal elimination .
The synthesis of 8 was designed by ring opening reaction of epoxide 17 and followed by hydrogenation of triple bond of the product. To test this strategy, compound 17 was prepared by the alkylation of 20 with lactone 15, followed by oxidation of the sulfide and therminal elimination. Treatment of epoxide 17 with 1-decyne using BuLi as the base gave compound 51 in 89% yield.

並列關鍵字

Rollicosin

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