Synthesis of Novel C/D Ring Modified Bile Acids
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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/7/2364 |
| _version_ | 1797438301516333056 |
|---|---|
| author | Roselis A. Landaeta Aponte Andreas Luxenburger Scott A. Cameron Alex Weymouth-Wilson Richard H. Furneaux Lawrence D. Harris Benjamin J. Compton |
| author_facet | Roselis A. Landaeta Aponte Andreas Luxenburger Scott A. Cameron Alex Weymouth-Wilson Richard H. Furneaux Lawrence D. Harris Benjamin J. Compton |
| author_sort | Roselis A. Landaeta Aponte |
| collection | DOAJ |
| description | 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 <i>C</i>-12 methyl and a <i>C</i>-13 to <i>C</i>-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 <i>O</i>-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation. |
| first_indexed | 2024-03-09T11:35:41Z |
| format | Article |
| id | doaj.art-2c1d56711d7d4f37b12a93a98705d3c3 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T11:35:41Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-2c1d56711d7d4f37b12a93a98705d3c32023-11-30T23:43:14ZengMDPI AGMolecules1420-30492022-04-01277236410.3390/molecules27072364Synthesis of Novel C/D Ring Modified Bile AcidsRoselis A. Landaeta Aponte0Andreas Luxenburger1Scott A. Cameron2Alex Weymouth-Wilson3Richard H. Furneaux4Lawrence D. Harris5Benjamin J. Compton6Ferrier Research Institute, Victoria University of Wellington, Lower Hutt 5010, New ZealandFerrier Research Institute, Victoria University of Wellington, Lower Hutt 5010, New ZealandFerrier Research Institute, Victoria University of Wellington, Lower Hutt 5010, New ZealandICE Group, New Zealand Pharmaceuticals Ltd., 68 Weld Street, RD2, Palmerston North 4472, New ZealandFerrier Research Institute, Victoria University of Wellington, Lower Hutt 5010, New ZealandFerrier Research Institute, Victoria University of Wellington, Lower Hutt 5010, New ZealandFerrier Research Institute, Victoria University of Wellington, Lower Hutt 5010, New ZealandBile 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 <i>C</i>-12 methyl and a <i>C</i>-13 to <i>C</i>-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 <i>O</i>-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation.https://www.mdpi.com/1420-3049/27/7/2364bile acidzinc carbenoidscyclopropanerearrangementdrug discovery |
| spellingShingle | Roselis A. Landaeta Aponte Andreas Luxenburger Scott A. Cameron Alex Weymouth-Wilson Richard H. Furneaux Lawrence D. Harris Benjamin J. Compton Synthesis of Novel C/D Ring Modified Bile Acids Molecules bile acid zinc carbenoids cyclopropane rearrangement drug discovery |
| title | Synthesis of Novel C/D Ring Modified Bile Acids |
| title_full | Synthesis of Novel C/D Ring Modified Bile Acids |
| title_fullStr | Synthesis of Novel C/D Ring Modified Bile Acids |
| title_full_unstemmed | Synthesis of Novel C/D Ring Modified Bile Acids |
| title_short | Synthesis of Novel C/D Ring Modified Bile Acids |
| title_sort | synthesis of novel c d ring modified bile acids |
| topic | bile acid zinc carbenoids cyclopropane rearrangement drug discovery |
| url | https://www.mdpi.com/1420-3049/27/7/2364 |
| work_keys_str_mv | AT roselisalandaetaaponte synthesisofnovelcdringmodifiedbileacids AT andreasluxenburger synthesisofnovelcdringmodifiedbileacids AT scottacameron synthesisofnovelcdringmodifiedbileacids AT alexweymouthwilson synthesisofnovelcdringmodifiedbileacids AT richardhfurneaux synthesisofnovelcdringmodifiedbileacids AT lawrencedharris synthesisofnovelcdringmodifiedbileacids AT benjaminjcompton synthesisofnovelcdringmodifiedbileacids |