Conformational analysis of 3‐oxo 5(10)‐unsaturated steroids. Single‐crystal X‐ray structure analysis of 17‐hydroxy‐7α‐methyl‐19‐nor‐17α‐pregn‐5(10)‐en‐20‐yn‐3‐one (Org OD 14)

Abstract

Abstract. Two crystallographically independent molecules with differing half-chair conformations of ring A were found in the analysis of Org OD 14. These results are compared with published X-ray structure analyses and Westheimer-type calculations of related steroids. It is concluded that the energy differences between the half-chair and envelope conformations of ring A of 3-0x0 5( 10)-unsaturated steroids are small. lntroductionThe conformation of the A-ring of 3-0x0 5(10)-unsaturated steroids has been the subject of a number of studies. A Westheimer-type calculation carried out by Cohen' indicated that estr-5( 1 O)-en-3-one 1 should exist in the half--chair form A, which has 0.9 kcal/mol less energy than the alternative half-chair B (Fig. I).In estra-5( l0),9( 1 I)-dien-3-one 2, however, calculations showed that the half-chair conformation B had 0.3 kcal/ mol less energy than conformation A. Half-chair conformations of ring A in 3-0x0* Aiithor to whom correspondence should be addressed.X-ray structure determination of 17P-(iodoacetoxy)estr--5( IO)-en-3-one 3' and of 17P-hydroxyestr-5( lO)-en-3-one 43 showed that for these two compounds the conformation of the A-ring, in the crystalline state, is an envelop C with C2 displaced to the a-side (Fig. 2). OH---C E C H rl4 5 R = H 6 R = CH, Two crystallographically independent molecules were found in an X-ray structure analysis of 17-hydroxy-1 %nor--I7m-pregn-5( lO)-en-20-yn-3-one 54. The A-rings in both 0 c -c=c+c

Solubility and dissolution studies of tibolone polymorphs

“…PXRD identification of crystals after recrystallization was carried out by comparing experimental data with calculated Bragg reflections from their single-crystal XRD structure (Declercq, Van Meerssche, Zeelen, 1984;Schouten, Kanters, 1991). The results are shown in Figure 2 and Table I. As observed in Figure 2 and Table I, the calculated Bragg peaks of form I match the experimental PXRD pattern of tibolone obtained by crystallizing in acetonewater and there was no unidentified peak, showing that form II and other crystalline phases are absent.…”

“…Recrystallization of tibolone form II was performed according to the literature (Sas, Van Doornum, 1991;Araujo et al, 2010a), with slight modifications: 5.0 g of FIGURE 1 -Perspective view showing the superposition of form I (conformers 1 and 2 in green and blue, respectively) and form II (in red) of tibolone. The molecular backbones were generated from the known crystal structures (Declercq, Van Meerssche, Zeelen, 1984;Schouten, Kanters, 1991). The hydrogen atoms were hidden for clarity.…”

“…To the best of our knowledge, two crystalline structures have been described for tibolone to date. The first crystal phase, named form I, was determined by Declercq, Van Meerssche, Zeelen (1984) in a P2 1 monoclinic space group (a = 6.542(2) Å, b = 41.213(9) Å, c = 6.678(2) Å, β = 101.64(2)°). The second known phase, named form II, was found some years later by Schouten, Kanters (1991) (triclinic P1, a = 6.542(2) Å, b = 6.677(<1) Å, c = 10.287(2) Å, α = 87.05(1)°, β = 80.09(2)°, γ = 79.17(2)°).…”

“…Calculated(Declercq, Van Meerssche, Zeelen 1984;Schouten, Kanters, 1991) and experimental PXRD pattern of forms I and II of tibolone.…”

Quantifying Isotibolone in Raw Materials of Tibolone

“…The tibolone crystal structures used in the Rietveld refinements were obtained from the Cambridge Structural Database (CSD) and have card IDs CIYRIL (monoclinic form) [13] and CIYRIL01 (triclinic form) [14]. The isotibolone crystal structure is that given by Ariel (CSD813039) [11].…”