近來的研究顯示，脂質抗原修飾物對於免疫系統在抗病毒、抑制腫瘤具有重要功能。本論文之研究方向為合成胺基神經醯胺，以作為核心化合物與各種樣的酸基耦合形成醯胺鍵以建立起分子庫篩選實驗。合成路徑以絲胺酸為起始物，先將胺基以Boc2O保護及甲基化後，再形成N,O-isopropylidine保護，接著將酯基還原成醇基，再以Swern oxidation的反應條件下，將其選擇性的氧化成醛類Garner’s aldehyde，建立擁有目標物主要骨架結構的中間產物。以Wittig Reaction設計不同長度sphingosine-based，及利用醯胺化的耦合方式，合成出醣脂質的建構單元"ceramide acceptor"。後續在官能基轉換時(OH → NH2)，以Tf2O作為離去基，受到醯胺鍵上的氫原子影響導致反應有環化現象的消去反應發生，無法預期得到胺基神經醯胺類似物，推測其有另一途徑的發生並與以討論之。
由於其脂質類似物具高度疏水性，且脂質抗原結構的改變可能導致抗原活性的增減，未來在生物分析上提供後續細胞活性試驗，以期望能高效率地篩選出具有潛力的化合物。

Recent studies have shown that the lipid antigens by the immune system is important for antiviral and antitumer. The aim of this study is synthesis of amino-ceramide as a core compound that coupling with various acids for constructing library of screenning experiment via amide bond formation. As the starting material is serin. Amino group of serin was first protected with Boc2O, followed by methylation and acetonidation to forming N,O-isopropylidine. Then reduced ester group into hydroxyl group. The main skeleton structure was constructed by Swern oxidation of selective oxidation to Garner’s aldehyde. Design different length sphingosine-based with Wittig Reaction, and utilized acylation to coupling via amide-bond formation, then synthesis of building block "ceramide acceptor" of glycolipid. While function group converted to amine compound (OH → NH2), then regard Tf2O as leaving group. As the hydrogen atom of amide bond would effect reaction, that lead to cyclolization phenomenon of elimination. It was unable to expect to get the amino-ceramide analog as target compound, that conjecture aboue mechanism with another pathway and discuss it.
Due to lipid analogs its high hydrophobic, and the change of lipid antigen structure may cause the increase and decrease of the antigen activation. In future, it provide bioassay studies to expect to find out the potential compound with high efficiency screening.

參考文獻
[1] a) Natori, T.; Koezuka, Y.; Tatsuo, H. Tetrahedron Lett., 1993, 34, 5591-5592
b) Akimoto, K.; Natori, T.; Morita, M. Tetrahedron Lett., 1993, 34, 5593-5596
c) Natori, T.; Morita, M.; Akimoto, K.; Koezuka, Y. Tetrahedron, 1994, 50, 2771-2784
[2] Morita, M.; Motoki, K.; Akimoto, K.; Natori, T.; Sakai, T.; Sawa, E.; Yamaji, K.; Koezuka, Y.; Kobayashi, E.; Fukushima, H. J. Med. Chem. 1995, 38, 2176-2187
[3] Ogretmen, B.; Hannun, Y. A. Nat. Rev. Cancer 2004, 4, 604-616
[4] a) Huwiler, A.; Kolter, T.; Pfeilschifter, J.; Sandhoff, K. Biochim. Biophys. Acta 2000, 1485, 63-99
b) Kolter, T.; Sandhoff, K. Angew. Chem. Int. Ed. 1999, 38, 1532-1568
[5] a) Brodesser, S.; Sawatzki, P.; Kolter, T. Eur. J. Org. Chem. 2003, 2021-2034
b)Liao, J.; Tao, J.; Lin, G.; Liu, D. Tetrahedron 2005, 61, 4715-4733
[6] Howell, A. R.; So, R. C.; Richardson S. K. Tetrahedron 2004, 60, 11327-11347
[7] Vankar, Y. D.; Schmidt, R. R. Chem. Soc. Rev. 2000, 29, 201-216
[8] Alfred H. Merrill, Jr, J. Biol. Chem. 2002, 277, 25843-25846
[9] Pyne, S.; Pyne, N. J. Biochem. J. 2000, 349, 385-402
[10] Toman, R. E.; Spiegel, S.; Faden, A. J. Neurotrauma 2000, 17, 891-898
[11] a) Okazaki, T.; Kondo, T.; Kitano, T.; Tashima, M. Cell. Signalling 1998, 10, 685-692
b) Birbes, H.; Bawab, S. E.; Obeid, L. M., Hannum, Y. A. Adv. Enzyme Regul. 2002, 42, 113-129
[12] Gonzalez-Aseguinolaza, G.; de Oliveira, C.; Tomaska, M.; Hong, S.; Bruna-Romero, O.; Nakayama, T.; Taniguchi, M.; Bendelac, A.; Van Kaer, L.; Koezuka, Y.; Tsuji, M. Proc. Natl. Acad. Sci. USA 2000, 97, 8461-8466
[13] Kakimi, K.; Guidotti, L. G.; Koezuka, Y.; Chisari, F. V. J. Exp. Med. 2000, 192, 921-930
[14] Hayakawa, Y.; Godfrey, D. I.; Smyth, M.J. Curr. Med. Chem. 2004, 11, 241-252
[15] a) Wilson, S. B.; Delovitch, T. L. Nat. Rev. Immunol. 2003, 3, 211-222
b) Taniguchi, M.; Harada, M.; Kojo, S.; Nakayama, T.; Wakao, H. Annu. Rev. Immunol. 2003, 21, 483-513
c)Van Kaer, L. Immunol. Cell Biol. 2004, 82, 315-322
[16] Crul, M.; Mathot, R. A. A.; Giaccone, G.; Punt, C. J. A.; Rosing, H.; Hillebrand, M. J. X.; Ando, Y.; Nishi, N.; Tanaka, H.; Schellens, J. H. M.; Beijnen, J. H. Cancer Chemother. Pharmacol. 2002, 49, 287-293
[17] Joyce, S.; Kaer, L. V. Curr. Opin. Immunol. 2003, 15, 95-104
[18] Wu, D.; Xing, G.-W.; Poles, M. A.; Horowitz, A.; Kinjo, Y.; Sullivan, B.; Bodmer-Narkevitch, V.; Plettenburg, O.; Kronenberg, M.; Tsuji, M.; Ho, D. D.; Wong, C. H. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 1351-1356
[19] Godfrey, D. I.; Hammond, K. J. L.; Poulton, L. D.; Smyth, M. J.; Baxter, A. G. Immunol Today, 2000, 21, 573-583
[20] Smyth, M. J.; Crowe, N. Y.; Hayakawa, Y.; Takeda, K.; Yagita, H.; Godfrey, D. I. Curr Opin Immunol, 2002, 14, 165-171
[21] Godfrey, D. I.; MacDonald, H. R.; Kronenberg, M.; Smyth, M. J.; Van Kaer, L. Nat. Rev. Immunol. 2004, 4, 231-237
[22] Fujio, M.; Wu, D.; Garcia-Navarro, R.; Ho, D. D.; Tsuji, M.; Wong, C.-H. J. Am. Chem. Soc. 2006, 128, 9022-9023
[23] Brutkiewicz, R. R.; Sriram, V. Crit. Rev. Oncol. Hematol. 2002, 41, 287-298
[24] Nicol, A.; Nieda, M.; Koezuka, Y.; Porcelli, S.; Suzuki, K.; Tadokoro, K.; Durrant, S.; Juji, T. Immunology, 2000, 99, 229-234
[25] a) Dolle, R. E. J. Comb. Chem. 2000, 2, 383-433
b) Dolle, R. E. J. Comb. Chem. 2005, 7, 739-798
[26] a) Boger, D. L.; Desharnais, J.; Capps, K. Angew. Chem. Int. Ed. 2003, 42, 4138-4176
b) Teague, S. J.; Davis, A. M.; Leeson, P. D.; Oprea, T. Angew. Chem. Int. Ed. 1999, 38, 3743-3748
[27] Goff, R. D.; Gao, Y.; Mattner, J.; Zhou, D.; Yin, N.; Cantu, C.; Teyton, L.; Bendelac, A.; Savage, P. B. J. Am. Chem. Soc. 2004, 126, 13602-13603
[28] Brik, A.; Wu, C. Y.; Wong, C. H. Org. Biomol. Chem. 2006, 4, 1446-1457
[29] Howell, A. R.; Ndakala, A. J. Curr. Org. Chem. 2002, 6, 365-391
[30] Liang, Y. F.; Andersch, J.; Bols, M. J. Chem. Soc., Perkin Trans. 1, 2001, 2136-2157
[31] Yang, G. L.; Schmieg, J.; Tsuji, M.; Franck, R. W. Angew. Chem. Int. Ed. 2004, 43, 3818-3822
[32] Xia, C.F.; Yao, Q. J.; Schumann, J.; Rossy, E.; Chen, W. L.; Zhu, L. Z.; Zhang, W. P.; De Libero, G.; Wang, P. G. Bioorg. Med. Chem. Lett. 2006, 16, 2195-2199
[33] Barbieri, L., Costantino, V.; Fattorusso, E.; Mangoni, A.; Aru, E.; Parapini, S.; Taramelli, D. Eur. J. Org. Chem. 2004, 468-473
[34] Azuma, H.; Tamagaki, S.; Ogino, K. J. Org. Chem. 2000, 65, 3538-3541
[35] Plettenburg, O.; Bodmer-Narkevitch, V.; Wong, C. H. J. Org. Chem. 2002, 67, 4559-4564
[36] Ndonye, R. M.; Izmirian, D. P.; Dunn, M. F.; Yu, K. O. A.; Porcelli, S. A.; Khurana, A.; Kronenberg, M.; Richardson, S.K.; Howell, A. R. J. Org. Chem. 2005, 70, 10260-10270
[37] Luo, S. Y.; Kulkarni, S. S.; Chou, C. H.; Liao, W. M.; Hung, S. C. J. Org. Chem. 2006, 71, 1226-1229
[38] Garner, P.; Park, J. M. J. Org. Chem. 1987, 52, 2361-2364
[39] Dondoni, A.; Perrone, D. Synthesis, 1997, 527-528
[40] Kim, S.; Song, S.; Lee, T.; Jung, S.; Kim, D. Synthesis 2004, 6, 847-850
[41] Villard, R.; Hammache, D.; Delapierre, G.; Fotiadu, F.; Buono, G.; Fantini, J. ChemBioChem 2002, 3, 517-525
[42] Kratzer, B.; Mayer, T. G.; Schmidt, R. R. Eur. J. Org. Chem. 1998, 291-298
[43] Berkers, C. R.; Ovaa, H. Trends Pharmacol. Sci. 2005, 26, 252-257
[44] Savage, P. B.; Teyton, L.; Bendelac, A. Chem. Soc. Rev., 2006, 35, 771-779
[45] De Libero, G.; Mori, L. Nat. Rev. Immunol. 2005, 5, 485-496