Organic Synthesis of New Secosteroids from Fucosterol, Its Intestinal Absorption by Caco-2 Cells, and Simulation of the Biological Activities of Vitamin D

We previously examined the cellular uptake of six types of vitamin D in human intestinal Caco-2 cells. Since vitamins D(5)–D(7) were commercially unavailable, we synthesized these compounds organically before studying them. This process led us to understand that new secosteroids could be generated as vitamin D candidates, depending on the sterol used as the starting material. We obtained two new secosteroids—compounds 3 and 4—from fucosterol in the current study. We investigated the intestinal absorption of these compounds using Caco-2 cells cultured in Transwells and compared the results with vitamin D(3), a representative secosteroid. The intestinal absorption of compound 4 was comparable to that of vitamin D(3). Compound 3 showed similar uptake levels but transported about half as much as vitamin D(3). These compounds demonstrated intestinal absorption at the cellular level. Vitamin D is known for its diverse biological activities manifest after intestinal absorption. Using PASS online simulation, we estimated the biological activity of compound 3’s activated form. In several items indicated by PASS, compound 3 exhibited stronger biological activity than vitamins D(2)–D(7) and was also predicted to have unique biological activities.