Practical Synthesis of 3β-Amino-5-cholestene and Related 3β-Halides Involving <i>i</i>-Steroid and Retro-<i>i</i>-Steroid Rearrangements

Abstract

Derivatives of 3β-amino-5-cholestene (3β-cholesterylamine) are of substantial interest as cellular probes and have potential medicinal applications. However, existing syntheses of 3β-amino-5-cholestene are of limited preparative utility. We report here a practical method for the stereoselective preparation of 3β-amino-5-cholestene, 3β-chloro-5-cholestene, 3β-bromo-5-cholestene, and 3β-iodo-5-cholestene from inexpensive cholesterol. A sequential i-steroid/retro-i-steroid rearrangement promoted by boron trifluoride etherate and trimethylsilyl azide converted cholest-5-en-3β-ol methanesulfonate to 3β-azido-cholest-5-ene with retention of configuration in 93% yield