Conformational design for 13 alpha-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 13 alpha-estra-1,3,5(10)-triene se ries were synthesized as precursors for biologically active compounds and c hiral Ligands for metal complexation. Conformational investigations of thes e and some other compounds via X-ray analysis and H-1 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 17 b eta-substituents or flattening of the D-ring are responsible for the twist- boat conformation, whereas compounds containing a 17 alpha-substituent or 1 7 keto group possess the classical conformation. By varying the substituent s, compounds with either of these conformations can be intentionally synthe sized. MO calculations confirmed the relative stability of the twist-boat c onformation.