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A‐Ring‐Modified 2‐Hydroxyethylidene Previtamin D 3 Analogues: Synthesis and Biological Evaluation
Author(s) -
HernándezMartín Alba,
Fernández Susana,
Verstuyf Annemieke,
Verlinden Lieve,
Ferrero Miguel
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201601263
Subject(s) - chemistry , calcitriol receptor , synthon , sonogashira coupling , moiety , stereochemistry , trifluoromethanesulfonate , ring (chemistry) , chemical synthesis , biological activity , combinatorial chemistry , biochemistry , receptor , organic chemistry , palladium , in vitro , catalysis
To investigate the biological profile of the previtamin form of vitamin D, we synthesized new analogues of 19‐ nor ‐1α,25‐dihydroxyprevitamin D 3 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.