Steroids and related studies. Part 60. Crystal and molecular structures of 17β-(2-hydroxyethyl)-3β-and 3α-pyrrolidino-17a-aza-D-homo-5-androstenes: HS-625 form 1, (3β-pyrrolidino) and HS-625 form 2 (mixed-3α and -3β-pyrrolidino epimers)

The crystal structures of two forms of 17-(2-hydroxyethyl)-3-pyrrolidino-17a-aza-D-homo-5-androstene (HS-625) are reported. In HS-625 (aqueous solvate) form 1, moleculeA, and HS-625 (anhydride) form 2, moleculeB, the pyrrolidine group is 3- substituted, while in HS-625 (anhydride) form 2, moleculeC has its pyrrolidine ring -substituted. HS-625 form 1 is orthorhombic, space groupP2₁2₁2₁, witha=7.089(4),b=11.502(6),c=28.975(16) Å,Z=4; form 2 is triclinic, space groupP1, witha=14.013(8),b=12.572(6),c=6.688(4) Å, =95.187(20), =103.491(21); =86.210(20)°,Z=2. MoleculesA andB have similar geometry, differences in moleculeC being related to strain caused by the unusual 3- ring substituent which also produces a pronounced kink in the backbone of the molecule. An unusual feature of the analysis of form 1 is the location of the water hydrogens in the difference electron density well above background. None of the OH hydrogens was located. Both structures are hydrogen bonded, but the pyrrolidine nitrogen N(31) in moleculeC is heavily congested and is unable to act as an acceptor. The hydroxyethyl side chain, important for activity, has a different conformation in the three molecules (t,g, t,-g, andt,t respectively).