CRYSTAL-STRUCTURE OF EDIOXYPREGN-4-ENE-3,20-DIONE-CENTER-DOT-2-PROPANOL (4 1) SOLVATE, C25H34O6F2-CENTER-DOT-1/4(C3H8O)/

In the course of our search for new anti-inflammatory glucocorticoster oids with improved therapeutic index, the 6 alpha,9 alpha-difluoro-11 beta,21-dihydroxy-16 alpha,17 alpha-propylmethylenedioxypregn-4-ene-3, 20-dione was synthesised, and the conformation, configuration and crys tallisation behaviour of one of its C(22) epimers, rofleponide, was st udied by X-ray single-crystal diffraction. The crystals, grown from a 2-propanol solution, had a body-centred tetragonal (I4, No. 79) unit c ell with a = b = 27.952(2) Angstrom, c = 6.3299(3) Angstrom, V-c = 494 5.6(6) Angstrom(3), D-c = 1.2989(2) g cm(-3) and F(000) = 2064, contai ning eight steroid and two solvent molecules. The alcoholic guest mole cules were found to be disordered, each one occupying two partly overl apping disorder positions with equal probability. The structure model was refined to R = 0.045 for 1199 observations with I > 2 sigma(I). Th e basic cyclopentanoperhydrophenanthrene steroid skeleton, containing four (A, B, C and D) rings, has a flat shape with the trans-anti-trans -anti-trans stereochemistry, like the naturally occurring steroid horm ones. The dioxolane (E) rings is fused to the cyclopentane (D) ring (a t the 16 alpha,17 alpha-positions) in a cis manner, with the angular h ydroxyacetyl substituent at C(17) approximately equatorially oriented to the D and axially to the E rings, and with the C(22)-propyl chain e quatorially attached to the dioxolane ring. Hence, the stereogenic cen tre at C(22), created during the formation of the cyclic 16 alpha,17 a lpha-acetal, has the absolute R configuration. The rofleponide molecul es in the crystal are linked via hydrogen bonds [O(21)... HO(3)] into infinite helical chains winding around the four-fold screw axes. The h elices are tied to each other by additional hydrogen bonds [O(11)... H O(20)], thus forming a three-dimensional H-bonded framework. This pack ing arrangement is stabilised by inclusion of the 2-propanol solvent, yielding a singular type of 'tubulato clathrate', where the alcoholic guests reside in channel-like cavities not inside but between the host helices without any noticeable interaction with the steroid molecules .