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Synthesis of Novel C/D Ring Modified Bile Acids

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journal contribution
posted 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.

History

Preferred citation

Landaeta 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

Journal title

Molecules

Volume

27

Issue

7

Publication date

2022-04-01

Pagination

2364-2364

Publisher

MDPI AG

Publication status

Published

Online publication date

2022-04-06

ISSN

1420-3049

eISSN

1420-3049

Article number

ARTN 2364

Language

en