CRYSTAL STRUCTURE AND CONFORMATION OF A BIOLOGICALLY ACTIVE STEROIDAL EPOXYQUINOL DERIVATIVE
A. Kapor1, B. Markov1, B. Ribar1, M. Strümpel2, D. Milic3 and B. Šolaja3
1Institute of Physics, Faculty of Sciences, Trg D. Obradoviæa 4, 21000 Novi Sad, Yugoslavia, e-mail: akapor@uns.ns.ac.yu 2Institut für Kristallographie, Freie Universität Berlin, Takustr. 6, D-14195, Berlin, Germany 3Faculty of Chemistry, University of Belgrade, P.O.Box 158, 11001 Belgrade, Yugoslavia
Keywords: steroidal quinones, crystal structure, conformation
During preparation of steroidal p-quinone derivatives for further structure-activity studies, analogous to those carried out for the avarone series [1], a pronounced regioselectivity was unexpectedly found in the nucleophilic addition reactions under acidic conditions. A previous pharmacological investigation indicated modest antimicrobial activity of some steroidal quinones and their derivatives against several bacterial strains.
In this paper we present the results of the structural and conformational analysis of an epoxyquinol derivative synthesized from quinol. The oxidation of estradiol 17-acetate using the m-CPBA / BzO2 / hn system in a refluxing CCl4 / acetone mixture occurred with 100% conversion, affording quinol and epoxyquinol in 50% and 22% yields respectively.
10b-hydroxy-4b,5b-epoxyestr-1-ene-3,17-dione was crystallized from a petroleum ether / aceton mixture. Needle-shaped crystals were obtained and single crystal data collected on a four circle STOE diffractometer with CuKa radiation. The crystals belong to a mono-clinic system with unit cell parameters a=9.745(5) Å, b=12.071(5) Å, c=14.342(5) Å, b=105.05(5) 0 and space group P21, Z=4, with two symmetry independent molecules in the asymmetric unit. 5508 reflections were measured of which 2954 are independent. The structure was solved by direct method using the program SIR92 and refined to a final R- factor 0.0308 for 2822 observed reflections using the program SHELXL93. Most hydrogen atoms were found from difference Fourier synthese and refined isotropically. For methyl hydrogens and peripheral hydrogen atoms (H15 1(2) and H16 1(2)) only their coordinates were refined and the temperature factor of the corresponding carbon atoms was assigned to them. Geometrical analysis confirmed the existance of two C-O double bonds, with distances C3-O3=1.216(4) Å(I), 1.217(4)Å(II) and C17-O17=1.212(3) Å(I), 1.212(4) Å (II) for molecules I and II respectively.
Conformational analysis of the steroid rings, by calculating puckering parameters and asymmetric factors, has shown that the symmetry independent molecules I and II are very similar. This was also confirmed by fitting the molecules to each other. The A ring in both molecules has a boat (B3,6) conformation, while rings B and C have chair (1C4) conformations and the five membered D ring has an envelope (E2) conformation. The energetically more stable conformation of the steroid rings in the molecule under study, compared to the methoxy-quinone derivative [2], indicate a less strained and hence lower energy conformation for this compound.
Analysis of the molecular packing in the unit cell has shown that beside the intramolecular hydrogen bonds there exists also a very strong intermolecular hydrogen bond (O10-H10…O17=2.871(3)Å in molecule I and 2.780(3)Å in molecule II) which results in a layered packing of the molecules parallel to the ab plane.
[1] R. Gozzolino, A. De Giulio, S.
De Rose, G. Strazzullo, M. J. Gašic, D. Sladic, M.
Zlatoviæ, J. Nat. Prod. 53, (1990), 699
[2] D. R. Milic, B. A. Šolaja, Lj. Došen- Micovic, B.
Ribar, A. Kapor, D.Sladic , M. J. Gašic, J. Serb. Chem.
Soc. 62 (9) (1997), 755- 768