Conformational design for 13alpha-steroids

The diastereomeric 16-bromo- and 16-azido-17-alcohols 5-8, 11, 12, 16, and 17 and 17-ketones 3, 4, 9, and 10 of the 13alpha-estra-1,3, 5(10)-triene series were synthesized as precursors for biologically active compounds and chiral ligands for metal complexation. Conformational investigations of these and some other compounds via X-ray analysis and (1)H NMR spectroscopy show the existence of compounds with the classical steroid conformation (ring C chair, restricted conformation of ring D) and such with an atypical ring C twist-boat and a flexible ring D conformation. It could be shown that 17beta-substituents or flattening of the D-ring are responsible for the twist-boat conformation, whereas compounds containing a 17alpha-substituent or 17-keto group possess the classical conformation. By varying the substituents, compounds with either of these conformations can be intentionally synthesized. MO calculations confirmed the relative stability of the twist-boat conformation.