Cobalt-assisted Medium Ring Cyclization for Solanoeclepin A and Taxoid Synthesis

林雅婷(Ya-Ting Lin)

指導教授 ： 磯部稔 ； 汪炳鈞

國立清華大學/理學院/化學系/博士(2015年)

https://doi.org/10.6843/NTHU.2015.00452

摘要

紫杉醇 Taxol 1和天然物 Solanoeclepin A 148的多碳骨架建構方法在最近十幾年受到有機化學加的關注. 紫杉醇 Taxol 1 及其衍生物 2, 3與4唯有潛力的抗腫瘤藥物; 而天然物Solanoeclepin A 148 具有刺激馬鈴薯中囊腫線蟲提早孵化的功能, 可用於農業病蟲害防治.
本論文將著重于雙環四烯 25 的十二圓環與四環雙烯 231 的七圓環骨架之建構. 經由八羰基二鈷 Co2 (CO)8 與炔進行錯合反應後得到的前驅物 23 與217 不止彎曲成易於反應的角度與方向, 在路易士酸的催化下更可利用尼古拉斯反應, 分子內細見-櫻井反應及普林斯羰基-烯反應進行還化反應得到產物四烯25與雙烯231, 最後脫去鈷試劑即官能基轉換可得十二圓環25與七圓環149.

關鍵字

紫杉醇 ； 八羰基二鈷 ； 尼古拉斯反應 ； 細見-櫻井反應 ； 普林斯羰基-烯反應

並列摘要

The synthesis of Taxol 1 and Solanoeclepin A 148 has been attracted chemist’s attention in recent three decades, due to the challenge to construct those poly-carbocyclic sub-structures. Taxol 1 and its derivatives 2, 3, and 4 are known as the potent agents against a wide range of tumor cells. Solanoeclepin A 148, on the other hand, shows a significant hatch-stimulating activity towards the potato cyst nematodes.
In this thesis, we have focused on the construction of twelve-membered carbocyclic substructure and seven-membered carbocyclic substructure of bicylic tetraene 25 and tetracyclic diene 231, respectively. The complexation of dicobalthexacarbonyl group played important roles not only in bending the molecule to suitable orientation to bring the moieties closer, but also using Nicholas effect and further Hosomi-Sakurai reaction and Prins-ene/halo reaction induced by Lewis acid to complete the synthesis of tetraene 25 and diene 231 frameworks.

並列關鍵字

Taxol ； dicobalt hexacarbonyl ； Nicholas reaction ； Hosomi-Sakurai reaction ； Prins-Carbonyl-ene reaction

參考文獻

55. Isobe, M.; Tsao, K. W.; Cheng, C. Y. Org. Lett. 2012, 14, 5274-5277.

References and notes

1. National Cancer Institute: http://dtp.nci.nih.gov/timeline/flash/success_stories/S2_taxol.htm

5. Schiff, P. B.; Horwitz, S. B. Proc. Natl. Acad. Sci. USA.1980, 77, 1561-1565.

1991, 83, 1797-1805.