Synthesis and vitamin D receptor affinity of 16-oxa vitamin D₃analogues

Abstract

Two novel 16-oxa-vitamin D3 analogues were synthesized using a Ti(ii)-mediated enyne cyclization/Cu-catalyzed allylation, Ru-catalyzed ring-closing metathesis, and a titanium-mediated stereoselective radical reduction of epoxide as the key steps.

Synthesis of C2-Alkoxy-Substituted 19-Nor Vitamin D3 Derivatives: Stereoselectivity and Biological Activity

“…The VDR binding affinity of C2-alkoxy-substituted 19-nor D 3 derivatives 7a – c was evaluated by the VDR competition assay with fluorescence polarization (PolarScreen™, Invitrogen) [ 27 ], and the results are summarized in Table 2 . In the case of C2α- 7a (2α-OMe), the binding affinity (mP value) was found to be 100.8% when the value for1,25D 3 was normalized to 100%.…”

The Centennial Collection of VDR Ligands: Metabolites, Analogs, Hybrids and Non-Secosteroidal Ligands

“…Figure 29 (2019-2020) [379][380][381][382][383]. It is known that 25(OH)D3, down-regulates SREBP (sterol regulatory element-binding protein) independently of VDR.…”

The Synthesis and Biological Evaluation of D-Ring-Modified Vitamin D Analogues

“…Removal of the C22-hydroxy group using the Barton reaction yielded 24-oxo compound 27, which was converted to 8-keto-CDring (28) in four steps. Coupling reactions using 28 and A-rings (24,29) were performed under the same conditions as in Scheme 3. Under the coupling conditions, the 24-oxo unit was inert, i.e., no chemical conversion was observed at the C24 position.…”

“…In 2019, Okamoto and coworkers reported the synthesis of 16-oxa-vitamin D 3 analogues ( 169 , 170 ) [ 29 ]. They synthesized the 16-oxa-CD-ring moiety ( 171 ) starting from 1-chloro-3-methylbut-2-ene ( 172 ) in 20 steps ( Scheme 16 ).…”