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8532770 
Journal Article 
Synthesis and Evaluation of Osteogenic Oxysterols as Hedgehog Pathway Activators 
Maschinot, CA; Corman, AR; Deberardinis, AM; Hadden, MK; , 
2016 
0 
ChemMedChem
ISSN: 1860-7179
EISSN: 1860-7187 
John Wiley and Sons Ltd 
11 
7 
679-686 
English 
26919682 
Oxysterols (OHCs) are metabolic byproducts of cholesterol that are known to function as agonists of the Hedgehog (Hh) signaling pathway. Previously, we reported 23(S)-hydroxycholesterol [23(S)-OHC, 4] as a potent activator of Hh signaling with the ability to functionally differentiate mouse embryonic fibroblasts to an osteogenic fate. To obtain 23(S)-OHC in quantities suitable for in vivo evaluation, we developed a revised synthetic route that decreases the number of steps and chromatographic purifications, and which also enhances the stereoselective nature of the synthesis. This new route also allows access to the C21 methyl group of the OHC scaffold, and several new analogues with varying stereochemistry at this location were evaluated for their ability to up-regulate the Hh pathway. 
Hedgehog; oxysterols; signal transduction; stereochemistry; structure-activity relationships