Strategies for the Synthesis of 19-nor-Vitamin D Analogs.

1 alpha,25-Dihydroxyvitamin D-3[1 alpha,25-(OH)(2)-D-3], the hormonally active form of vitamin D-3, classically regulates bone formation, calcium, and phosphate homeostasis. In addition, this hormone also exerts non-classical effects in a wide variety of target tissues and cell types, such as inhibition of the proliferation and stimulation of the differentiation of normal and malignant cells. However, to produce these actions, supraphysiological doses are required resulting in calcemic effects that limit the use of this natural hormone. During the past 30 years, many structurally modified analogs of the 1 alpha,25-(OH)(2)-D(3)have been synthesized in order to find derivatives that can dissociate the beneficial antiproliferative effects from undesired calcemic effects. Among these candidates, 1 alpha,25-(OH)(2)-19-nor-D(3)analogs have shown promise as good derivatives since they show equal or better activity relative to the parent hormone but with reduced calcemic effects. In this review, we describe the synthetic strategies to obtain the 19-nor-D(3)derivatives and briefly describe their physiological activities.