| 研究生: |
俞得喜 Yudhi Dwi Kurniawan |
|---|---|
| 論文名稱: | Progress in the Synthesis of Brevipolide |
| 指導教授: |
侯敦仁
Duen-Ren Hou |
| 口試委員: | |
| 學位類別: |
碩士 Master |
| 系所名稱: |
理學院 - 化學學系 Department of Chemistry |
| 論文出版年: | 2013 |
| 畢業學年度: | 101 |
| 語文別: | 英文 |
| 論文頁數: | 105 |
| 中文關鍵詞: | 環丙烷 、非鏡像選擇性 、環合置換反應 、烯烴置換反應 |
| 外文關鍵詞: | cyclopropane, diastereoselectivity, ring closing metathesis, cross metathesis |
| 相關次數: | 點閱:11 下載:0 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
我們的研究是合成出 Brevipolide 。經由七步反應得到中間產物III.8 ,總產率為 18% 。利用Michael-Initiated Ring Closure reactions得到環丙烷並具有部分非鏡像選擇性。醇上接有不同保護基會有不同的選擇性,例如:以 TBS和 MOM保護的不飽和銅得到已 R,R 為主的環丙烷,比例為 6.2 :1 。另一方面,以縮醛保護的銅得到以S,S 為主的環丙烷,比例為 1 :2.4 。將MOM保護去掉的化合物 III.9 ,可用 X-ray 繞射來鑑定環丙烷上立體結構。
This study is aimed to achieve the synthesis of Brevipolide. So far, the key intermediate III.8 was prepared in 7 steps with an overall yield of 18%. Michael-Initiated Ring Closure reactions were the key step to provide the cyclopropane moiety with diastereoselectivity. The facial selectivity was different for the substrates with different hydroxyl protecting groups, i.e. the TBS- and MOM-protected alfa,beta-unsaturated ketone gave the major R,R-cyclopropane (dr, 6.2:1), on the other hand, the acetonide-protected ketone provided the S,S-cyclopropane (dr, 1:2.4). The stereo-assignment of the R,R-cyclopropane was confirmed by the X-ray crystallography of the subsequent MOM-deprotected product III.9.
(1) Wallock, N.J., Preparation of Cyclopropanes via Organoiron
Methodology, Dissertation, 2004
(2) Donaldson, W.A., Tetrahedron, 2001, 57, 8589
(3) a) Saläun, J., Top. Curr. Chem., 2000, 207, 1 b) Saläun , J.;
Baird, M.S., Curr. Med. Chem., 1995, 2, 511 c) Gnad, F.; Reiser,
O., Chem. Rev., 2003, 103, 1603 d) Stammer, C.H., Tetrahedron,
1990, 46, 2231 e) Burgess , K.; Ho , K–K.; Moye-Sherman, D.,
Synlett, 1994, 575
(4) a) Asai, A.; Hasegawa, A.; Ochiai, K.; Yamashita, Y.; Mizukami,
T., J. Antibiotics, 2000, 53, 81 b) Asai, A.; Tsujita, T.; Sharma,
S.V.; Yamashita, Y.; Akinaga, S.; Funakoshi, M.; Kobayashi, H.;
Mizukami, T., Biochem. Pharmacology, 2004, 67, 227 c)
Mizukami, T.; Asai, A.; Yamashita, Y.; Katahira, R.; Hasegawa,
A.; Ochiai, K.; Akinaga, S., Eur. Patent 768317, 1997
(5) Friesen, R.W.; Ducharme, Y.; Ball, R.G.; Blouin, M.; Boulet, L.;
Côté, B.; Frenette, R.; Girard, M.; Guay, D.; Huang, Z.; Jones,
T.R.; Laliberté, F.; Lynch, J.J.; Mancini, J.; Martins, E.; Masson,
P.; Muise, E.; Pon, D.J.; Siegl, P.K.S.; Styhler, A.; Tsou, N.N.;
Turner, M.J.; Young, R.N.; Girard, Y., J. Med. Chem., 2003, 46,
2413
(6) Monn, J.A.; Valli, M.J.; Massey, S.M.; Hansen, M.M.; Kress,
T.J.; Wepsiec, J.P.; Harkness, A.R.; Grutsch, J.L.; Wright, Jr., 48
R.A.; Johnson, B.G.; Andis, S.L.; Kingston, A.; Tomlinson, R.;
Lewis, R.; Griffey, K.R.; Tizzano, J.P.; Schoepp, D.D., J. Med.
Chem., 1999, 42, 1027
(7) Deng, Y.; Balunas, M.J.; Kim, J.A.; Lantvit, D.D.; Chin, Y.W.;
Chai, H.; Sugiarso, S.; Kardono, L.B.S.; Fong, H.H.S.; Pezzuto,
J.M.; Swanson, S.M.; de Blanco, E.J.C.; Kinghorn, A.D. J. Nat.
Prod., 2009, 72, 1165–1169
(8) Suárez-Ortiz, G.A.; Cerda-García-Rojas, C.M.; Hernández-
Rojas, A.; Pereda-Miranda, R., J. Nat. Prod., 2013, 76, 72−78
(9) Narayanam, J.M.; Stephenson, C.R., Chem. Soc. Rev., 2011, 40,
102
(10) Yoon, T.P.; Ischay, M.A.; Du, J., Nat. Chem., 2010, 2, 527
(11) Kavarnos, G.J.; Turro, N.J., Chem. Rev., 1986, 86, 401
(12) Calderon, N. Acc. Chem. Res., 1972, 5, 127-132
(13) Calderon, N.; Chen, H.Y.; Scott, K.W., Tetrahedron Lett., 1967,
8, 3327-3329
(14) Grubbs, R.H.; Brunck, T.K., J. Am. Chem. Soc., 1972, 94, 2538-
2540
(15) Hérisson, J. L.; Chauvin, Y., Makromol. Chem., 1971, 141, 161-
176
(16) Schaverien, C.J.; Dewan, J.C.; Schrock, R.R., J. Am. Chem. Soc.,
1986, 108, 2771-2773
(17) Murdzek, J.S.; Schrock, R.R., Organometallics, 1987, 6, 1373-
1374
(18) Schrock, R.R.; Krouse, S.A.; Knoll, K.; Feldman, J.; Murdzek,
J.S.; Yang, D.C., J. Mol. Catal., 1988, 46, 243-253 49
(19) Schrock, R.R.; Murdzek, J.S.; Barzan, G.C.; Robbis, J.; DiMare,
M.; O’Regan, M., J. Am. Chem. Soc., 1990, 112, 3875-3886
(20) Nguyen, S.T.; Johnsson, L.K.; Grubbs, R.H., J. Am. Chem. Soc.,
1992, 114, 3974-3975
(21) Schwab, P.; France, M.B.; Ziller, J.W.; Grubbs, R.H., Angew.
Chem. Int. Ed. Engl., 1995, 34, 2039-2041
(22) Scholl, M.; Ding, S.; Lee, C.W.; Grubbs, R.H., Org. Lett., 1999,
1, 953-956
(23) (a) Handbook of metathesis; Grubbs, R.H., Ed.;Wiley-VCH:
Weinheim, Germany, 2003 (b) Ivin, K.J.; Mol, J.C. Olefin
Metathesis and Metathesis Polymerization; Academic Press:
New York, 1997
(24) (a) Carillo, A.; Cane, R., J. Polym. Sci., Part A: Polym. Chem.,
2004, 42, 3352 (b) Buchmeiser, M.R., Chem. Rev., 2000, 100,
1565 (c) Grubbs, R.H.; Tumas W., Science, 1989, 243, 907
(25) Dieltiens, N., Novel Metathesis Applications: Synthesis of New
Azaheterocycles by Homogeneous Catalysis, Thesis, 2007
(26) Lebel, H.; Marcoux, J.F.; Molinaro, C.; Charette, A.B., Chem.
Rev., 2003, 103, 977-1050
(27) (a) Caine, D., Tetrahedron, 2001, 57, 2643 (b) Li, J.; Liu, Y.-C.;
Deng, J.-G., Tetrahedron: Asymmetry, 1999, 10, 4343
(28) Krollpfeiffer, F.; Hartmann, H., Chem. Ber., 1950, 83, 90
(29) (a) Corey, E.J.; Chaykovsky, M., J. Am. Chem. Soc., 1962, 84,
867 (b) Corey, E.J.; Chaykovsky, M., J. Am. Chem. Soc., 1965,
87, 1353 (c) Corey, E.J.; Jautelat, M., J. Am. Chem. Soc., 1967, 50
89, 3912 (d) Takahashi, T.; Yamashita, Y.; Doi, T.; Tsuji, J., J.
Org. Chem., 1989, 54, 4273
(30) (a) Trost, B.M.; Melvin, L.S., Jr. Sulfur Ylides, Emerging
Synthetic Intermediates; Academic Press: New York, 1975 (b)
Yanovskaya, L.A.; Dombrovskii, V.A. Russ. Chem. Rev., 1975,
44, 154 (c) Johnson, C.R. In Comprehensive Organic Chemistry;
Barton, D.H.R., Ollis, W.D., Eds.; Pergamon: Oxford, 1979; Vol.
3, p 247 (d) Gololobov, Y.G.; Nesmeyanov, A.N.; Lysenko, V.P.;
Boldeskul, I.E., Tetrahedron, 1987, 43, 2609 (e) Li, A.-H.; Dai,
L.-X.; Aggarwal, V.K., Chem. Rev., 1997, 97, 2341 (e) La Porta,
E.; Piarulli, U.; Cardullo, F.; Paio, A.; Provera, S.; Seneci, P.;
Gennari, C., Tetrahedron Lett., 2002, 43, 761
(31) Samet, A.V.; Shestopalov, A.M.; Nesterov, V.N.; Semenov,
V.V., Russ. Chem. Bull., 1998, 47, 127
(32) (a) Mulzer, J.; Kappert, M., Angew. Chem., Int. Ed., 1983, 22, 63
(b) Mulzer, J.; Kappert, M., Angew. Chem. Suppl., 1983, 23
(33) (a) Krief, A.; Dumont,W.; Pasau, P.; Lecomte, P., Tetrahedron,
1989, 45, 3039 (b) Stork, G.; Kahn, M., Tetrahedron Lett., 1983,
24, 3951
(34) Krief, A.; Lecomte, P., Tetrahedron Lett., 1993, 34, 2695
(35) (a) Krief, A.; Provins, L.; Froidbise, A., Tetrahedron Lett., 1998,
39, 1437 (b) Krief, A.; Provins, L.; Froidbise, A., Synlett, 1999,
1936
(36) Ma, D.; Ma, Z., Tetrahedron Lett., 1997, 38, 7599
(37) Burke, S.D.; Sametz, G.M., Org. Lett., 1999, 1, 71-74 51
(38) Caroline, C.R.; Benazza, M.; Fréchou, C.; Demailly, G.,
Carbohydrate Research., 1997, 303, 359-365
(39) Lu, K.J.; Chen, C.H.; Hou, D.R., Tetrahedron, 2009, 65, 225-
231
(40) (a) Chou, C,-Y.; Hou, D.-R., J. Org. Chem., 2006, 71, 9887-
9890 (b) Voigtritter, K.; Ghorai, S.; Lipsshutz, B.H., J. Org.
Chem., 2011, 76, 4697-4702
(41) Liu, C.W.; Yeh, T.C.; Chen, C.H.; Yu, C.C.; Chen, C.S.; Hou,
D.R.; Guh, J.H., Tetrahedron, 2013, 69, 2971-2976
(42) Ma, D.; Ma, Z., Tetrahedron Lett., 1997, 38, 7599-7602
(43) Pisani, L.; Superchi, S.; D’Elia, A.; Scafato, P.; Rosini, C.,
Tetrahedron, 2012, 68, 5779-5784
(44) Yadav, J.S.; Mandal, S.S., Tetrahedron Lett., 2011, 52, 5747–
5749
(45) Ghosh, S.; Ghosh, S.; Sarkar, N., J. Chem. Sci., 2006, 118, 223–
235
(46) (a) Bruckner, R., 2002, Advanced Organic Chemistry: Reaction
Mechanisms, Harcourt/Academic Press, USA, 348 (b) Carey,
F.A.; Sundberg, R.J., 2007, Advanced Organic Chemistry Part A:
Structure and Mechanism Fifth Edition, Springer, New York