Vitamin D is a group of seco-steroids with diverse bioactivities. An enormous amount of effort was expended by medicinal chemists to search for VitD analogs that could exhibit pro-differentiating and antiproliferative effects on normal and cancer cells as well as immunomodulatory effects without causing hypercalcemia. Such programs resulted in the synthesis of >3000 modified VitD analogs and the commercial launch of about a dozen new medicines (e.g., Hectorol, Zemplar, Calcijex, Rocaltrol). Calcipotriol (DovonexTM, LEO Pharma) is currently the most successful VitD analog and is prescribed for the treatment of psoriasis, an autoimmune skin disease. The goal of this study was two-fold: (1) the design of an enantioselective, scalable, and convergent approach to calcipotriol not wedded to semisynthesis; and (2) the use of such a platform as a means to create known and novel VitD analogs in a modular fashion. Extensive explorations from both academic and industrial arenas in this area provided a useful foundation for this study and set the stage for a completely unique approach. Some of the highlights of the current route include: 1) symmetry recognition to scalably access ring A; 2) development of an unprecedented asymmetric enone 1,4-borylation methodology; 3) strategic application of radical retrosynthesis for both ring annulation and substitution to address the C/D rings; 4) implementation of a semi-pinacol rearrangement to deliver the thermodynamically unfavored 6,5-trans ring fusion; 5) late-stage side-chain installation; 6) scalability of the route with inexpensive materials (p-cresol and cyclohexanone).