本篇主旨在於合成出神經醯胺類似物，並用它來合成α-galcer- amide 類似物。在這裡我們取絲胺酸(L-Serine) 作為起始物，一開始我們將絲氨酸的胺基做Boc 保護基，在不經管柱層析的條件下，利用偶氮甲烷(diazomethane) 在乙醚溶液中進行反應，使得絲氨酸的酸基做酯化反應。接著取2,2-dimethoxypropane 在含有TsOH•H2O 的甲苯溶液中加熱進行迴流反應，使得經過保護的絲胺酸做OH 和NH 保護基。隨後利用LiAlH4 在THF 溶液中，將酯基還原成醇基，並在Swern Oxidaton 的條件下將醇基氧化成醛基。總合五步反應(產率：38%)可得到Garner’s aldehyde 以作為合成神經醯胺類似物的骨架。
在得到Garner’s aldehyde 後，我們利用Wittig reaction 將一個長碳鏈與Garner’s aldehyde 的醛基結合，隨後取產率較高的(Z)-form 化合物，利用四氧化鋨(OsO4) 的催化，在水溶液中進行了碳碳雙鍵的雙醇化氧化反應。並取產率較高雙醇化合物以三氟醋酸(trifloroacetic acid) 去掉acetonide 和Boc 保護基得到phytosphingosine。最後我們將長碳鏈的酸製備成NHS-ester(N-hydroxysuccinimide ester)，並和phytosphingosine 進行鍵結生成醯胺基，得到神經醯胺類似物，並將其醇基做Ac保護，以利光譜分析之用。
此化合物未來在實驗室應用在合成及生物分析上，預計除了合成α-galceramide 類似物之外，並由於其高度的酯溶性，因此可運用在發展微脂粒的藥物傳輸上，並可經由些微的化學結構修飾以發展相關化學合成及生物分析的應用。

The aim of this study is to prepare ceramide analogues as building block for synthesizing α-galactosyl ceramide analogue. As the starting material, L-serine was protected at its amino group with (Boc)2O. Without chromatography, N-Boc-serine was converted to the methyl ester derivative with diazomethane in ether. After protection of the amino and hydroxy groups with 2, 2-dimethoxy propane under reflux, the product: oxazolidine ester was treated with LiAlH4 to restore OH group. Following Swern oxidation, Garner’s aldehyde was obtained in total 38% yield via five steps.
While Garner’s aldehyde was in hand, the subsequent Wittig reaction to introduce aliphatic chain at formyl group was forwarded. Dihydroxylation at this (Z)-form olefin under catalysis of OsO4 was employed to afford the syn addition product in 92% yield with 80% diaseteromeric excess. Following the removal of acetonide group with TFA, the phytosphingosine obtained was coupled with N-hydroxy- succinimide ester to introduce the amide-bond linkage. Afterwards, for obtaining satisfactory analytical spectra of the ceramide analogue, purification was prerequisite and this was achieved by protection of the hydroxy groups with acetic anhydride.
As this ceramide analogue was in hand, the subsequent synthesis of alpha-galceramide and the relevant biological assay was performable. Further application of this compound includes drug delivery and cancer vaccine, in former case the self-formed liposome enwrapping the drug in aqueous solution served as the carrier.

1a. Kakimi, K.; Guidotti, L. G.; Koezuka, Y.; Chisari, F.
V. J. Exp. Med. 2000, 192, 921.

1b. Baron, J. L.; Gardiner, L.; Nishimura, S.; Shinkai, K.;
Locksley,R.; Ganem, D. Immunity 2002, 16, 583.

1c. Howell, A. R.; So, R. C.; Richardson, S. K. Tetrahedron
2004, 60, 11327.

1d. Zhou, D.; Mattner, J.; Cantu, C., III; Schrantz, N.;
Yin, N.; Gao, Y.; Sagiv, Y.; Hudspeth, K.; Wu, Y.-P.;
Yamashita, T.; Teneberg, S.; Wang, D.; Proia, R. L.;
Levery, S. B.; Savage, P. B.; Teyton, L.; Bendelac, A.
Science 2004, 306, 1786.

1e. Kinjo, Y.; Wu, D.; Kim, G.; Xing, G. W.; Poles, M. A.;
Ho, D. D.; Tsuji, M.; Kawahara, K.; Wong, C. -H.;
Kronenberg, M. Nature 2005, 434, 520.

1f. Mattner, J., Debord, K. L., Ismail, N., Goff, R. D.,
Cantu, C., 3rd, Zhou, D., Saint Mezard, P., Wang, V.,
Gao, Y., Yin, N., Hoebe, K., Schneewind, O., Walker,
D., Beutler, B., Teyton, L., Savage, P. B., and
Bendelac, A. Nature 2005, 434, 525.

1g. Murata, K.; Toba, T.; Nakanishi, K.; Takahashi, B.;
Yamamura, T.; Miyake, S.; Annoura, H. J. Org. Chem.
2005, 70, 2398-2401.

1h. 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.

1i. Yu, K. O. A.; Porcelli, S. A. Immunol. Lett. 2005, 100,
42.

1j. Fan, G.-T.; Pan, Y.-s.; Lu, K.-C.; Cheng, Y.-P.; Wong,
C.-H.; Lin, W.-C.; Lin, C.-H.; Fang, J.-M.; Lin, C.-C.;
Tetrahedron 2005, 61, 1855

1k. Yao, Q.; Song, J.; Xia, C.; Zhang, W.; Wang, P. G. Org.
Lett. 2006. 8. 911-914

1l. Luo, S.-Y.; Kulkarni, S. S.; Chou, C.-H.; Liao, W.-M.;
Hung S.-C. J. Org. Chem. 2006, 71, 1226.

1m. David, C. Y.; D. Branch M. Glycobiology. 2006. 16. 103.

2. Vankar, Y. D.; Schmidt, R. R. Chem. Soc. Rev. 2000, 29,
201.

3. Howell, A. R.; Ndakala, A. J. Curr. Org. Chem. 2002, 6,
365.

4. Gregory, G. I.; Malkin, T. J. Chem. Soc. 1951, 2453-.

5. Grob, C. A.; Jenny, E. F.; Utzinger, H. Helv. Chim. Acta
1951, 34, 2249.

6. Grob, C. A.; Jenny, E. F. Helv. Chim. Acta 1952, 35,
2106.

7. Prostenik, M.; Stanacev, N. Z. Naturwissenschaften 1956,
43, 447.

8. Prostenik, M.; Mayhofer-Orescanin, B.; Ries-Lesic, B.;
Stanacev, N. Z. Tetrahedron 1965, 21, 651.

9. Newman, H. Chem. Phys. Lipids 1974, 12, 48.

10. Liang, X.; Andersch, J.; Bols, M. J. Chem. Soc., Perkin
Trans. 1 2001, 2136.

11. Garner, P.; Park, J. M. J. Org. Chem. 1987, 52, 2361.

12. McKillop, A.; Taylor, R. J. K.; Watson, R. J.; Lewis,
N. Synthesis, 1994, 31.

13. Roush, W. R.; Hunt, J. A. J. Org. Chem., 1995, 60, 798.

14. Marshall, J. A.; Seletsky B. M.; Coan, P. S. J. Org
Chem., 1994, 59, 5139.

15. Dondoni, A.; Perrone, D., Synthesis, 1997, 527.

16. Dondoni, A.; Fantin, G.; Fogagnolo, M.; Pedrini, P.
J.Org. Chem. 1990, 55, 1439.

17. Imashiro, R.; Sakurai, O.; Yamashita, T.; Horikawa, H.
Tetrahedron 1998, 54, 10657.

18. Shirota, O.; Nakanishi, K.; Berova, N. Tetrahedron
1999, 55, 13643.

19. Azuma, H.; Tamagaki, S.; Ogino, K. J. Org. Chem. 2000,
65, 3538.

20. Goff, R. D.; Gao, Y.; Mattner, J.; Zhou, D.; Yin, N.;
Cantu, C., III; Teyton, L.; Bendelac, A.; Savage, P. A.
J. Am. Chem. Soc. 2004, 126, 13602.

21. Kim, S.; Song, S.; Lee, T.; Jung, S.; Kim, D. Synthesis
2004, 6, 847.

22. Alper, P. B.; Hung, S. C.; Wong, C. H. Tetrahedron
Lett. 1996, 37, 6029.