Synthesis of Novel C/D Ring Modified Bile Acids
journal contributionposted on 2023-02-22, 22:39 authored by RA Landaeta Aponte, Andreas LuxenburgerAndreas Luxenburger, Scott CameronScott Cameron, A Weymouth-Wilson, Richard FurneauxRichard Furneaux, Lawrence HarrisLawrence Harris, Benjamin ComptonBenjamin Compton
Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure–activity relationships and define compounds that activate these receptors selectively. Towards this, access to large quantities of a chenodeoxycholic acid derivative bearing a C-12 methyl and a C-13 to C-14 double bond provided an interesting scaffold to investigate the chemical manipulation of the C/D ring junction in bile acids. The reactivity of this alkene substrate with various zinc carbenoid species showed that those generated using the Furukawa methodology achieved selective α-cyclopropanation, whereas those generated using the Shi methodology reacted in an unexpected manner giving rise to a rearranged skeleton whereby the C ring has undergone contraction to form a novel spiro–furan ring system. Further derivatization of the cyclopropanated steroid included O-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation.
Preferred citationLandaeta Aponte, R. A., Luxenburger, A., Cameron, S. A., Weymouth-Wilson, A., Furneaux, R. H., Harris, L. D. & Compton, B. J. (2022). Synthesis of Novel C/D Ring Modified Bile Acids. Molecules, 27(7), 2364-2364. https://doi.org/10.3390/molecules27072364
Online publication date2022-04-06
Article numberARTN 2364
bile acidzinc carbenoidscyclopropanerearrangementdrug discoveryBile Acids and SaltsChenodeoxycholic AcidOxidation-ReductionSteroidsStructure-Activity RelationshipDigestive DiseasesOrganic ChemistryMedicinal and Biomolecular Chemistry not elsewhere classifiedTheoretical and Computational Chemistry not elsewhere classifiedOrganic Chemistry