A‐Ring‐Modified 2‐Hydroxyethylidene Previtamin D3 Analogues: Synthesis and Biological Evaluation. Issue 3 (3rd January 2017)

• Record Type: Journal Article
• Authors: Hernández‐Martín, Alba; Fernández, Susana; Verstuyf, Annemieke; Verlinden, Lieve; Ferrero, Miguel
• Is Part Of: European journal of organic chemistry. Issue 3(2017)
• Page Start: 504
• Page End: 513
• Publication Date: 2017-01-03
• Subjects: Vitamins -- Total synthesis -- Chiral pool -- Biological activity -- Structure‐activity relationships; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201601263
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : To investigate the biological profile of the previtamin form of vitamin D, we synthesized new analogues of 19‐ nor ‐1α, 25‐dihydroxyprevitamin D3 bearing a 2‐hydroxyethylidene moiety at the A‐ring. The target compounds were prepared by convergent synthesis using a Sonogashira coupling between an A‐ring enyne synthon and a CD‐ring/side‐chain vinyl triflate. We have demonstrated the versatility of shikimic acid as a starting material for the synthesis of the A‐ring precursors. The binding affinity to vitamin D receptor (VDR) and human vitamin D binding protein (hDBP), and the MCF‐7 cell antiproliferative activity were evaluated. Abstract : The synthesis of previtamin D3 analogues with a 2‐hydroxyethylidene group in the A‐ring is described. The strategy involves coupling of a dienyne precursor of the A‐ring derived from shikimic acid with an enol triflate of the CD‐ring/side‐chain fragment. The binding affinity to vitamin D receptor (VDR) and human vitamin D binding protein (hDBP), and the MCF‐7 cell antiproliferative activity is discussed.