Synthesis of 6-s-cis and 6-s-trans A-Ring Modified Vitamin D Analogues

Title:Synthesis of 6-s-cis and 6-s-trans A-Ring Modified Vitamin D Analogues

Volume: 14 Issue: 21

Author(s): Susana Fernandez, Alba Hernandez-Martín, Tania Gonzalez-García and Miguel Ferrero

Affiliation:

Keywords: 6-s-cis Analogues, 6-s-trans Analogues, A-Ring Analogues, Previtamin D, Vitamin D, Synthesis.

Abstract: Vitamin D, through its hormonally active form 1α,25-dihydroxyvitamin D₃ [1α,25- (OH)₂-D₃], exhibits a much broader spectrum of bio logical activities than expected in the endocrine system. However, 1α,25-(OH)₂-D₃ causes hypercalcemia a t pharmacologically r elevant doses wh ich forms a major obstacle in the clinical development of this compound. As a result, considerable effort has been made toward the synthesis of potential chemotherapeutic structurally related congeners with dissociation of beneficial effects from their toxic effects. Most of the analogues prepared have modifications on the upper side chain, more accessible from a synthetic point of view. Modifications of the A-ring are less extensive, although A-ring analogues exhibit a unique biological profile. This seco steroid can undergo a rotation around the 6,7 carbon-carbon single bond generating a wide array of molecular shapes, extending from the 6-s-cis to the more stable extended 6-s-trans conformation, which plays an important role in modulating the different biological activities of vitamin D. We review here, the synthetic strategies for the preparation of Vitamin D analogues with modific ations on the A-ring, including 6-s-cis locked derivatives that became of interest to further probe the less well investigate membrane actions of 1α,25-(OH)₂-D₃ for structure-activity relationship studies.

Cite this article as:

Fernandez Susana, Hernandez-Martín Alba, Gonzalez-García Tania and Ferrero Miguel, Synthesis of 6-s-cis and 6-s-trans A-Ring Modified Vitamin D Analogues, Current Topics in Medicinal Chemistry 2014; 14 (21) . https://dx.doi.org/10.2174/1568026615666141208101751