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Conformational analysis of sterols: Comparison of X-ray crystallographic observations with data from other sources

  • Symposium: Sterol Analysis Held at the AOCS Annual Meeting in New York, NY, April 29, 1980
  • Published:
Lipids

Abstract

Crystallographic data on over 400 steroids collected in theAtlas of Steroid Structure provide information concerning preferred conformations, relative stabilities and substituent influence on the interactive potential of steroid hormones. Analysis of these data indicates that observed conformational details are intramolecularly controlled and that the influence of crystal packing forces is negligible. Crystallographic data on the orientation of the progesterone side chain contradict published force-field calculations. In 84 of 88 structures having a 20-one substituent, the C(16)−C(17)−C(20)−O(20) torsion angle is between 0° and −46°. The 4 torsion angles that lie outside this range do so because of a 16β-substituent and not because of crystal packing forces. Not one of the 88 structures is found to have a conformation in which the C(16)−C(17)−C(20)−O(20) torsion angle is within ±15° of the most commonly calculated minimum energy value. The narrow range of side chain conformations seen in very different crystalline environments in the 88 crystal structure determinations and the predictable substituent influence apparent in the data strongly suggest that crystallographically observed conformers seldom deviate from minimum energy positions, regardless of hypothetical broad energy minima, metastable states and small barriers to rotation. The 96 crystallographically independent determinations of the cholestane 17-side chain show that the chain has 4 principal conformations (A∶B∶C∶D), occurring in the ratio 69∶8∶8∶11. Although the fully extended side chain is clearly the energetically most favored one, in 16 observations of cholesterol itself only 6 are in the extended conformation. Some of the correlated conformational changes in the chains can be rationalized on the basis of model studies, but others apparently result from subtle intramolecular forces. The unsaturated B ring provides another element of flexibility in the structure of cholesterol. The 5-ene B ring is normally observed in an 8β,9α-half-chair conformation. However, in structures containing more than one molecule in the crystallographic asymmetric unit, at least one of the 2 molecules is found to differ significantly from this form. It may be that this inherent flexibility is responsible for the presence of conformationally distinct molecules in the same crystal. The intermolecular interaction observed in the crystal structure of cholesterol and its fatty acid derivatives illustrate the type of interaction between the steroid ring system and hydrocarbon chains that can be expected in membrane bilayers.

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References

  1. “Atlas of Steroid Structure”, Vol. I, edited by W.L. Duax and D.A. Norton, Plenum Press, New York, 1975.

    Google Scholar 

  2. Klyne, W., and V. Prelog, Experientia 16:521 (1960).

    Article  CAS  Google Scholar 

  3. Nassimbeni, L.R., A.G. Orpen, G.M. Sheldrick, J.C. van Niekerk and G.M.L. Cragg, Acta Crystallog. B33:3326 (1977).

    Article  Google Scholar 

  4. Craven, B.M., and N.G. Guerina, Chem. Phys. Lipids 29:157 (1979).

    Article  Google Scholar 

  5. B. Dahlen, Chem. Phys. Lipids 23:179 (1979).

    Article  CAS  Google Scholar 

  6. Guerina, N.G., and B.M. Craven, J. Chem. Soc. Perkin II 414 (1979).

    Google Scholar 

  7. Pascher, I., and S. Sundell, Acta Chem. Scand. A31:767 (1977).

    Article  Google Scholar 

  8. Krstanovic, I., and L. Karanovic, Cryst. Struct. Commun. 8:517 (1979).

    CAS  Google Scholar 

  9. Sawzik, P., and B.M. Craven, Acta Crystallog. B35:789 (1979).

    Article  Google Scholar 

  10. Guy, J.J., F.H. Allen, O. Kennard and G.M. Sheldrick, Acta Crystallog. B33:1236 (1977).

    Article  Google Scholar 

  11. Hoard, L.G., L.G. Shieh and C.E. Nordman, Nature 267:287 (1977).

    Article  PubMed  Google Scholar 

  12. Sawzik, P. and B.M. Craven, Acta Crystallog. B35:895 (1979).

    Article  Google Scholar 

  13. Ducruix, A. and C. Pascard-Billy, Acta Crystallog. B32:76 (1976).

    Article  Google Scholar 

  14. Abrahamsson, S. and B. Dahlen, Chem. Phys. Lipids 20:43 (1977).

    Article  PubMed  CAS  Google Scholar 

  15. Cooper, A. and D.A. Norton, J. Org. Chem. 33:3535 (1968).

    Article  CAS  Google Scholar 

  16. Harrison, H.R., D.C. Hodgkin, E.N. Maslen and W.A.S. Motherwell, J. Chem. Soc. C 1275 (1971).

  17. Trinh-Toan, R.C. Ryan, G.L. Simon, J.C. Calabrese, L.F. Dahl and H.F. DeLuca, J. Chem. Soc., Perkin II 393 (1977).

    Google Scholar 

  18. Conner, B.N., E.J. Parish, G.J. Schroepfer and F.A. Quiocho, Chem. Phys. Lipids 18:240 (1977).

    Article  PubMed  CAS  Google Scholar 

  19. Phillips, G.N., Jr., F.A. Quiocho, R.L. Sass, P. Werness, H. Emery, F.F. Knapp, Jr., and G.J. Schroepfer, Jr., Bioorg. Chem. 5:1 (1976).

    Article  CAS  Google Scholar 

  20. Altenburg, H., D. Mootz and B. Berking, Acta Crystallog. B28:567 (1972).

    Article  CAS  Google Scholar 

  21. Sheldrick, G.M., E. Oeser, M.R. Caira, L.R. Nassimbeni and R.A. Pauptit, Acta Crystallog. B32:1984 (1976).

    Article  Google Scholar 

  22. Geise, H.J., and C. Romers, Acta Crystallog. 20:257 (1966).

    Article  CAS  Google Scholar 

  23. Chandross, R.J., and J. Bordner, Acta Crystallog. B34:2872 (1978).

    Article  Google Scholar 

  24. Griffin, J.F., M. Erman, W.L. Duax, D.S. Watt and F.A. Carey, J. Org. Chem. 40:2956 (1975).

    Article  PubMed  CAS  Google Scholar 

  25. Geise, H.J. and C. Romers, Acta Crystallog. 20:257 (1966).

    Article  CAS  Google Scholar 

  26. Duax, W.L., and V. Cody, unpublished results.

  27. Nassimbeni, L.R., J.C. Russell and G.M.L. Cragg, Acta Crystallog. B33:3755 (1977).

    Article  Google Scholar 

  28. Fuhrer, H., L. Lorenc, V. Pavlovic, G. Rihs, G. Rist, J. Kalvoda and M. Lj Mihailovic, Helv. Chem. Acta 62:1770 (1979).

    Article  CAS  Google Scholar 

  29. Russell, J.C., L.R. Nassimbeni and G.M.L. Cragg, Acta Crystallog. B33:2128 (1971).

    Article  Google Scholar 

  30. Kemlo, W.S., J.C. van Niekerk and L.R. Nassimbeni, Cryst. Struct. Commun. 8:107 (1979).

    CAS  Google Scholar 

  31. Kirfel, A., A. Will, R. Brennecke and R. Tschesche, Acta Crystallog. B33:895 (1977).

    Article  Google Scholar 

  32. Bosworth, N., A. Emke, J.M. Midgley, C.J. Moore, W.B. Whalley, G. Ferguson and W.C. Marsh, J. Chem. Soc., Perkin I 805 (1977).

    Article  Google Scholar 

  33. deKok, A.J., and C. Romers, Acta Crystallog. B30:1695 (1974).

    Article  Google Scholar 

  34. Nassimbeni, L.R., A.G. Orpen, G.M. Sheldrick, J.C. van Niekerk and G.M.L. Cragg, Acta Crystallog. B33:3326 (1977).

    Article  Google Scholar 

  35. Suginome, H., and A. Furusaki, J. Chem. Soc., Chem. Commun. 782 (1979).

  36. Craven, B.M., and G.T. DeTitta, J. Chem. Soc., Perkin II 814 (1976).

    Google Scholar 

  37. Losman, A., and R. Karlsson, Acta Crystallog. B34:2586 (1978).

    Article  Google Scholar 

  38. Pettit, G.R., J.J. Einck and J.C. Knight, J. Am. Chem. Soc. 100:7781 (1978). (Submitted to Acta Crystallog.)

    Article  CAS  Google Scholar 

  39. Vani, G.V., and K. Vijayan, Mol. Cryst. Liq. Cryst. 51:253 (1979).

    CAS  Google Scholar 

  40. Spike, T.E., A.H.J. Wang, I.C. Paul and G.J. Schroepfer, Jr., J. Chem. Soc. Chem. Commun. 477 (1974).

  41. DeLuca, P., M. DeRose, L. Minale, R. Puliti, G. Sodano, F. Giordana and L. Mozzarella, J. Chem. Soc., Chem. Commun. 825 (1973).

  42. Harrison, H.R., D.C. Hodgkin, E.N. Maslen and W.A.S. Motherwell, J. Chem. Soc. C:1275 (1971).

  43. Geise, H.J., C. Romers and E.W.M. Rutten, Acta Crystallog. 20:249 (1966).

    Article  CAS  Google Scholar 

  44. Van Niekerk, J.C. and L.R. Nassimbeni, Acta Crystallog. B33:3582 (1977).

    Article  Google Scholar 

  45. Duax, W.L., unpublished results.

  46. Gilliland, G.L., M.E. Newcomer, E.J. Parish, G.J. Schroepfer and F.A. Quiocho, Acta Crystallog. B33:3117 (1977).

    Article  Google Scholar 

  47. Carlisle, C.H., and D. Crowfoot, Proc. Roy. Soc. A. 184:64 (1945).

    CAS  Google Scholar 

  48. Pattabhi, V., and B.M. Craven, J. Lipid Res. 20:753 (1979).

    PubMed  CAS  Google Scholar 

  49. Akiyama, T., D. Pedder, J.V. Silverton, J.I. Seeman and H. Ziffer, J. Org. Chem. 40:3675 (1975).

    Article  PubMed  CAS  Google Scholar 

  50. Duchamp, D.J., C.G. Chidester, J.A.F. Wickramasenghe, E. Caspi and B. Yagen, J. Am. Chem. Soc. 93:6283 (1971).

    Article  PubMed  CAS  Google Scholar 

  51. Burki, H., and W. Nowacki, Z. Kristallogr. 108: 206 (1956).

    Article  CAS  Google Scholar 

  52. deKok, A.J., F. Boomsma and C. Romers, Acta Crystallog. B32:2492 (1976).

    Article  Google Scholar 

  53. Sawzik, P., and B.M. Craven, Acta Crystallog. B36:215 (1980).

    Article  CAS  Google Scholar 

  54. Vani, G.V., and K. Vijayan, Mol. Cryst. Liq. Cryst. 51:253 (1979).

    CAS  Google Scholar 

  55. Craven, B.M., and N.G. Guerina, Chem. Phys. Lipids 29:91 (1979).

    Article  Google Scholar 

  56. Mootz, D., and B. Berking, Acta Crystallog. B26:1362 (1970).

    Article  CAS  Google Scholar 

  57. Chandross, R.J., and J. Bordner, Acta Crystallog. B33:2934 (1977).

    Article  Google Scholar 

  58. Craven, B.M., Nature 260:727 (1976).

    Article  PubMed  CAS  Google Scholar 

  59. Trinh-Toan, H.F. DeLuca and L.F. Dahl, J. Org. Chem. 41:3476 (1976).

    Article  CAS  Google Scholar 

  60. Cesario, M.J. Guilhem, C. Pascard and J. Redel, Tetrahedron Lett. 12:1097 (1978).

    Article  Google Scholar 

  61. Huber, R., and W. Hoppe, Chem. Ber. 98:2403 (1965).

    PubMed  CAS  Google Scholar 

  62. Dammeier, B., and W. Hoppe, Chem. Ber. 104: 1660 (1971).

    PubMed  CAS  Google Scholar 

  63. Mez, H.C., G. Rist, O. Ermer, L. Lorenc, J. Kalvoda and M. Lj. Mihailovic, Helv. Chem. Acta. 59:1273 (1976).

    Article  CAS  Google Scholar 

  64. Polishchuck, A.P., M. Yu. Antipin, R.G. Gerr, V.I. Kulishov, Yu. T. Struchkov and L.G. Derkach, Cryst, Struct. Commun. 9:263 (1980).

    Google Scholar 

  65. Suginome, H., A. Furusaki, K. Kato and T. Matsumato, Tetrahedron. Lett. 32:2757 (1975).

    Article  Google Scholar 

  66. Gorter, S., Acta Crystallog. B32:2730 (1976).

    Article  Google Scholar 

  67. Duax, W.L., C.M. Weeks and D.C. Rohrer, in “Topics in Stereochemistry,” Vol. 9, edited by E.L. Eliel and N. Allinger, Wiley Interscience, New York, 1976, pp. 271–283.

    Google Scholar 

  68. Wellman, K.M., and C. Djerassi, J. Am. Chem. Soc. 87:60 (1965).

    Article  CAS  Google Scholar 

  69. Schmit, J.-P., and G.G. Rousseau, J. Steroid Biochem. 9:909 (1978).

    Article  PubMed  CAS  Google Scholar 

  70. Barton, D.H.R., F. McCapra, P.J. May and F. Thudium, J. Chem. Soc. 1297 (1960).

  71. Wing, R.M., W.H. Okamura, A. Rego, M.R. Pirio and A.W. Norman, J. Am. Chem. Soc. 97:4980 (1975).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Medical Foundation of Buffalo, Inc., 73 High Street, 14203, Buffalo, NY

    William L. Duax, Jane F. Griffin, Douglas C. Rohrer & Charles M. Weeks

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  1. William L. Duax
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  2. Jane F. Griffin
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  3. Douglas C. Rohrer
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Duax, W.L., Griffin, J.F., Rohrer, D.C. et al. Conformational analysis of sterols: Comparison of X-ray crystallographic observations with data from other sources. Lipids 15, 783–792 (1980). https://doi.org/10.1007/BF02534032

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  • DOI: https://doi.org/10.1007/BF02534032

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