臺灣博碩士論文加值系統

中藥蟬花是麥角菌科(Clavicipitaceae)大草蟬草菌(Cordyceps cicadae Shing)寄生在山蟬(Cicada flammata Dist)幼蟲的真菌，藥材包括其子實體及蟲體，是作為治療小兒驚厥，心悸及鎮定的中藥。先前研究從蟬花的蟲體部分分離出白僵菌酮(bassiatin)、白僵菌酮甲(bassiatin A) 、白僵菌素(beauvericin) 、白僵菌素甲(beauvericin A)及白僵菌素乙(beauvericin B)等成分。
大多數這些化合物也在其他真菌裡發現，文獻報導bassiatin 是一種抗血小板凝集的成分，beauvericin是許多種菌類會合成的有毒成分，這種毒素可以殺死蚊子的幼蟲，亦有抗血小板凝集的功效。
Beauvercin是由三個bassiatin分子所組成，先前文獻雖有報導beauvercin之全合成，但是步驟很簡略，也沒有數據，因此我們針對beauvericin做為全合成目標，以N-tert-butoxycarbonyl-N-methyl-L-
phenylalanine 與 benzyl D--hydroxyisovalerate為起始物，經七個
步驟合成beauvericin。

Cordyceps cicadae Shing (Clavicipitaceae) is a parasitic fungus on the larvae of Cicada flammata Dist. Both the ascocarps and the insect-body portions of Cordyceps cicadae under the name Chan-hua have been used as a drug for childhood convulsion, palpitation, and sedation. In previous study, two dioxomorpholines (bassiatin and bassiatin A) and three cyclodesipeptides (beauvericin, beauvericin A, and beauvericin B) were isolated from the insect-body portion of the fungi Cordyceps cicadae. Many of them were also found in other fungi. Bassiatin was found as a platelet aggregation inhibitor. Beauvericin was reported to possess antimicrobial and mitochondrial activity. In an earlier attempt beauvericin was synthesized from carbobenzoxy-N-methyl-L-phenylalanine and tert-butyl-D-α-hydroxyisovalerate but no detailed procedures were given. In this thesis, a convenient synthetic method was established to prepare beauvericin starting with N-tert-butoxycarbonyl-N-methyl-L-phenylalanine and benzyl D-α-hydroxyisovalerate.

中文摘要 i
英文摘要 ii
壹、前言 1
貳、實驗儀器與藥品試劑
2-1實驗儀器 4
2-2藥品試劑 5
參、合成方法 7
肆、實驗步驟 10
伍、結果與討論 19
陸、參考文獻 21
柒、附圖 23

陸、參考文獻
1. Juangsu New Medical College. Zhong Yao Da Ci Dian (Dictionary Chinese Materia Medica), Shanghai Scientific and Technological Publishers, Shanghai, pp. 2557-2558, 1979.
2. Weng, S.-C.; Chou, C.-J.; Lin, L.-W.; Tsai, W.-J.; Kuo, Y.-C. Immunomodulatory Funtions of Extracts from the Chinese Medicinal Fungus Cordyceps cicadae, J Ethnopharmacology 2002, 83, 79-85.
3. Kuo, Y.-C.; Lin, L.-C.; Don, M.-J.; Liao, H.-F.; Tsai, Y.-P.; Lee, G.-H.; Chou, C.-J. Cyclodesipeptide and Dioxomorpholine Derivatives Isolated from the Insect-body Portion of the Fungus Cordyceps cicadae, J Chin. Med. 2002, 13, 209-219.
4. Kagamizono, T., Nishino. E., Matsumoto, K., Kawashima, A., Kishimoto, M., Sakai. N., He. B.-M., Chen. Z.-X., Adachi. T., Morimoto. S., Hanada. K. Bassiatin, A New Platelet Aggregation Inhibitor Proguced by Beauveria bassiana K717, J. Antibiotics 1995, 48, 1407-1412.
5. Gupta, S.; Montllor, C.; Hwang, Y.-S. Isolation of Novel Beauvercin Analogues from the Fungus Beauveria bassiana, J. Nat. Prod. 1995, 58, 733-738.
6. Ovchinnikov, Y. A.; Ivanov, V. T.; Mikhaleva, I. I. The Synthesis and Properties of Beauvercin, Tetrahedron Lett. 1971, 2, 159-162.
7. Hurt, C. R.; Lin, R.; Henry, (R)-4-Amino-5-oxo-1,3,4,5-tetrahydrobenz[cd]indole, An Advanced Intermediate Containing the Tricyclic Core of the Ergots, J. Org. Chem. 1999, 64, 225-233.
8. Thoen, J. C.; Lipton, M. A. The Effects of N-Methylation on the Enantioselectivity of Catalysis by Cyclo[(R)-His-(R)-Phe], Tetrahedron Asymmetry 1997, 8, 3947-3954.
9. Hoffman, R. V.; Tao, J. An Improved Enantiospecific Synthesis of Statine and Statine Analogs via 4-(N,N-Dibenzylamino)-3-keto Esters, J. Org. Chem. 1997, 62, 2292-2297.
10. Meyers, A. I.; Tavares, F. X. Oxidation of Oxazolines and Thiazolines to Oxazoles and Thiazoles. Application of the Kharasch-Sosnovsky Reaction, J. Org. Chem. 1996, 61, 8207-8215.