我們以PC-SPARTAN工作軟體，利用半經驗式AM1的量子計算方法，探討環烷類分子(C12H24、C14H28、C16H32、C18H36、C20H40)的構形特性，以及環狀抗癌藥物Epothilones(C27H41O5SN、C26H41O7SN)及大環內酯類抗生素Macrolides(C28H46O9N2、C27H49O9N)的構形與生化活性之間的關係。
　　計算結果顯示，環烷類C-C鍵的torsional energy都相當低約為20 kJ/mol。表示環烷類相當容易受到外力影響而產生許多構形變化。從構形上來看，除了扭動位置的二面角有較大的變化之外，其他位置幾乎不受到影響。經過三環(cyclopropyl)修飾的C-C鍵比一般C-C鍵有較大的torsional energy，代表三環附近的構造比較rigid，不太容易改變此位置的構形。
　　從環烷類構形上的分析發現，同時扭轉多個二面角可使環烷類上原子的排列產生移動，雖然構形上的變化不大，但其碳－氫鍵卻因C-C鍵的扭動而發生擺動現象。具有三環構造的環烷類能固定環的區域構形，故三環附近的碳－氫鍵擺動的角度會比較小。
　　在藥物的構形分析上，具有三環結構的藥物分子其側鍊和官能基的擺動幅度因三環固定區域構形而大幅度減小，相較於非三環結構的藥物分子其側鍊和官能基的大幅度擺動，因此具有三環結構的藥物分子的側鍊和官能基與活性中心作用的機會大增，我們認為這是造成藥物活性差異的重要原因。

　　We discuss the conformations of cycloalkanes(C12H24、C14H28、C16H32、C18H36、C20H40) and the relations between conformations and biochemical activities of both Epothilones and Macrolides by semi-emprcial AM1 quantum mechanical calculation methods with PC-SPARTAN.
　　The calculation results show that the torsional energy of C-C bond in cycloalkanes is so low, even lower than 20 kJ/mol, reveals cycloalkanes are easily affected by external force so as to occur many conformation variations.
　　In conformation, only dihedral angle locating the torsional position changes larger than any other positions where is less affected. The cyclopropyl C-C bond has the larger torsional energy than usual ones, which means the conformation near cycloprpyl is more rigid, and not too easily be changed.
　　For cycloalkanes, the results of conformational analysis indicate that the simultaneous torsions of several dihedral angles can move the arrangement of carbon atoms in cycloalkanes. Despite the variation is not so apparent, the C-H bonds oscillate for the torsion of C-C bond. Those cyclopropyl cycloalkanes can fasten the local conformation of cycloalkanes, so that the oscillating angles of C-H bonds near cyclopropyl would be smaller.
　　From the conformation analysis of medicines, the flapping range of the side chain and functional groups in the medical cyclopropyl compounds would reduce largely because of the rigid cyclopropyl local conformation. Compared with the large flap of other conformations' medical side chain and functional groups, those which get cyclopropyl conformations in them are the medical compounds whose side chain and functional groups react with the active center much possibly. We think this is the main reason which results the difference of activities of medicines.

(1) Rawdah T N., Tetrahedron, 1991, 47(40), 8579～8586.

(2) Anet F A L,Rawdah T N., J.Am.Chem.Soc., 1978, 100(23), 7166～7171.

(3) Anet F A L et al., J. Am. Chem. Soc., 1972, 94(26), 9250～9251.

(4) Dale J., Acta Chem. Scand., 1973, 27, 1115～1129;1130～1148.

(5) Dunitz J. D., Shearer H. M. M., Proc. Chem. Soc., 1958, 348～349;CA.53:12770b.

(6) Dunitz J. D., Shearer H. M. M., ibid, 1959, 268～269;CA.54:5205c.

(7) Fuhrer H. and Gunthard Hs H., Helv. Chem. Acta, 1965, 48(23), 236～251.

(8) Arndt R., J. Chem. Phys., 1965, 43(6), 1885～1887.

(9) Bixon M. and Lifson S., Tetrahedron, 1967, 23, 769～784.

(10) Saunders M., Tetrahedron, 1967, 23, 2105～2113.

(11) Moller M et al., J. Am. Chem. Soc., 1984, 106(18), 5093～5099.

(12) Saunders M., J. Comp. Chem., 1991, 12(6), 645～663.

(13) Allinge N. L., Yun Y. H. and Lii J. H., J. Am. Chem. Soc., 1989, 111(23), 8551～8566.

(14) G. Höfle, N. Bedorf, K. Gerth, H. Reichenbach(GBF), Chem. Abstr., 1993, 120, 52841

(15) G. Höfle, N. Bedorf, K. Gerth, H. Reichenbach(GBF), Chem. Abstr., 1993, 119, 180598

(16) D. M. Bollag, P. A. McQueney, J. Zhu, O. Hensens, L. Koupal, J. Liesch, M. Goetz, E, Lazarides, C. M. Wood, Cancer Res., 1995, 55, 2325-2333

(17) D. M. Bollag, Exp. Opin. Invest. Drugs 1997, 6, 867-873

(18) P. B. Schiff, J. Fant, S. B. Horwitz, Nature, 1979, 277, 665-667

(19) D. M. Bollag, P. A. McQueney, J. Zhu, O. Hensens, L. Koupal, J. Liesch, M. Goetz, E, Lazarides, C. M. Wood, Cancer Res., 1995, 55, 2325-2333

(20) R. J. Kowalski, p. Giannakakou, E. Hamel, J. Biol. Chem. 1997, 272, 2534-2541

(21) M. C. Wani, H. L. Taylor, M. E. Wall, P. Coggon, A. T. McPhail, J. Am. Chem. Soc., 1971, 93, 2325-2327

(22) T. Junod, Life, 1992, 15, 71-76

(23) “Taxane Anticancer Agents：Basic Science and Current Status”： G. I. Georg, T. T. Chen, I. Ojima, D. M. Wyas, ACS Symposium Series 1995, 583, 35

(24) G. Höfle, N. Bedorf, H. Steinmetz, D. Schomburg, K. Gerth, Riechenbach, Angrew. Chem, 1996, 108, 1671-1673

(25) G. Höfle, N. Bedorf, H. Steinmetz, D. Schomburg, K. Gerth, Riechenbach, Angrew. Chem. Int. Ed. Engl. 1996, 35, 1567-1569

(26) S. F. Victory, D. G. Vander Velde, R. K. Jalluri, G. L. Grunewald, G. I. Georg, Bioorg. Med. Chem. Lett. 1996, 6, 893-898

(27) Richard E. Taylor, Jaroslav Zajicek, J. Org. Chem. 1999, 64, 7224-7228

(28) Valluri, M.; Hindupur, R. M.; Bijoy, P.; Labadie, G.; Jung, J.-C.; Avery, M. A., Org. Lett. 2001, 3(23), 3607-3609

(29) Taylor, R. E.; Chen, Y., Org. Lett. 2001, 3(14), 2221-2224

(30) Zhu, B.; Panek, J. S., Org. Lett. 2000, 2(17), 2575-2578

(31) Regueiro-Ren, A.; Borzilleri, R. M.; Zheng, X.; Kim, S.-H.; Johnson, J. A.; Fairchild, C. R.; Lee, F. Y. F.; Long, B. H.; Vite, G. D., Org. Lett. (Communication) 2001, 3(17), 2693-2696

(32) O'Connor, S. E.; Chen, H.; Walsh, C. T., Biochemistry 2002, 41(17), 5685-5694

(33) Elliott, R. L.; Pireh, D.; Griesgraber, G.; Nilius, A. M.; Ewing, P. J.; Bui, M. H.; Raney, P. M.; Flamm, R. K.; Kim, K.; Henry, R. F.; Chu, D. T. W.; Plattner, J. J.; Or, Y. S., J. Med. Chem. 1998, 41(10), 1651-1659

(34) Irini Akritopoulou-Zanze, Thomas J. Sowin, J. Comb. Chem. 2001, 3, 301-311

(35) 黃雯英，成功大學化學研究所碩士論文，民國90年，105頁

(36) Mash, E. A.; Gregg, T. M.; Stahl, M. T.; Walters, W. P.; J. Org. Chem., 1996, 61(8), 2738-2742

(37) Mash, E. A.; Gregg, T. M.; Stahl, M. T., J. Org. Chem., 1997, 62(11), 3715-3721

(38) Pawar, D. M.; Smith, S. V.; Mark, H. L.; Odom, R. M.; Noe, E. A., J. Am. Chem. Soc., 1998, 120(41), 10715-10720