Significance
Vitamin D (VitD), a group of secosteroids, has proved to be an essential molecule in supporting overall human health. Structurally, modification at C20 has led to the discovery of novel analogs with a wide range of biological targets. Among them, calcipotriol (Daivonex; LEO Pharma) has been a proven clinical drug for the treatment of psoriasis, an autoimmune skin disease. This work relates to an improved process for the preparation of intermediates useful for the preparation of a range of VitD derivatives, including calcipotriol, and to processes for preparation of calcipotriol. Strategic bond disconnections enable de novo syntheses of both A- and CD-rings not wedded to semisynthesis.