利用九環內醯胺合環反應合成(±)-Quebrachamine

許世文(Shih-Wen Hsu)

指導教授 ： 侯敦仁

國立中央大學/理學院/化學系/碩士(2013年)

摘要

利用溴取代吲哚化合物3c和炔烴化合物8當做起始物經由Sonogashira耦合反應合成得到天然物 (±)-Quebrachamine (22)。在九環內醯胺化反應中發現順式雙鍵的結構有助於反應，並且證實起始物為單鍵時無法成功合成九環內醯胺。也發現利用鋁氫化鋰(lithium aluminum hydride, LAH)反應可以同時去掉胺甲酸酯的保護和還原內醯胺至胺基。最後利用已知具有立體選擇性的水解方法合成起始物，進一步經過chiral pool的合成方式得到天然物(-)-Quebrachamine。

關鍵字

白堅木胺 ； 九環內醯胺化

並列摘要

(±)-Quebrachamine (22) was synthesized using compound 3c and 8 as starting materials. Then skeleton of the natural product compound 16 was synthesized by Sonogashira coupling.

Cis double bond conformation of compound 19 was discovered that can help us to synthesize nine-membered ring lactam. The lactam not being successfully obtained from single bond compound 18 with the same reaction condition was proved .

The reduction of aromatic carbamate and lactam simultaneously by using Lithium Aluminum Hydride(LAH) was discovered.

參考文獻

1. O. Hesse. Ann., 1882, 211 , 249.

2. (a) G. Stork, J. E. Dolfini. J. Am. Chem. Soc. 1963, 85, 2872 – 2873.

(b) Iain Coldham, Adam J. M. Burrell, Laura E. White, Harry Adams, and Niall Oram. Angew. Chem. Int. Ed. 2007, 46, 6159 –6162.

(c) Ziegler, F. E.; Kloek, J. A.; Zoretic, P. A. J. Am. Chem. Soc. 1969, 91, 2342.

3. Phil S. Baran and Ryan A. Shenvi. J. Am. Chem. Soc. 2006, 128, 14028-14029