Method of locking 1alpha-OH of vitamin D compounds in axial orientation

摘要

A method of modifying or altering the structure of a 1alpha-hydroxylated vitamin D compound to increase its biological activity by altering the conformational equilibrium of the A-ring to favor a chair conformation that presents the 1alpha-hydroxyl in the axial orientation. This is accomplished by either locking the A-ring chair conformation in a geometry having an axially orientated 1alpha-hydroxyl, or by the addition of one or more substituents to the A-ring which interact with other substituents in the molecule or on the A-ring to provide a driving force to the A-ring to adopt a chair conformation which presents the 1alpha-hydroxyl in the axial orientation.