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.

Abstract ………………………………………………………………….. i
Abstract in Chinese ……………………………………………………… ii
Table of Contents ……………………………………………………….. iii
List of Figure ……………………………………………………………. iv
List of Table ……………………………………………………………... v
List of Spectra …………………………………………………………… vi
Chapter I Introduction ………………………………………………… 1
1.1 Origin of research ………………………………………………….. 1
1.2 Purpose of study ……………………………………………………. 4
Chapter II Literature Review ………………………………………….. 5
2.1 New 5,6-Dihydro-α-pyrone Derivatives
from Hyptis brevipes ……………………………………………….. 5
2.2 Metathesis Reaction ……………………………………………….. 6
2.3 Cyclopropanation ………………………………………………….. 11
Chapter III Result and Discussion ……………………………………… 21
3.1 Retrosynthetic Approach for Brevipolide ………………………… 21
3.2 Results and Discussion …………………………………………….. 22
Chapter IV Experimental ………………………………………………. 32
Chapter V Conclusions and Future Perspective ……………………… 46
5.1 Conclusions ………………………………………………………. 46
5.2 Perspective Future ………………………………………………… 46
Reference ………………………………………………………………… 47
Appendix ………………………………………………………………… 52

(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