Scalable Synthesis of an Acid Stable Analogue of Hippuristanol
Hippuristanol is a marine derived steroidal natural product with promising anticancer activity. However, instability at low pH has precluded its development as an efficient therapy. We addressed this limitation by replacing one of the oxygen atoms of the spiroketal moiety with a carbon atom. Key steps in the synthesis include a Meyer-Schuster/Nazarov cascade, a hypoiodite mediated oxyfunctionalization, and the late-stage installation of a hydroxyl group on the C-ring of the steroid.
Authors
- Morag E. Watson (ORCID: https://orcid.org/0000-0003-1854-6805)
- Jennifer R. Baker (ORCID: https://orcid.org/0000-0002-9560-301X)
- Laurent Rigoreau
- Haibin Mao
- Katherine A. Fowler (ORCID: https://orcid.org/0000-0002-7734-1407)
- Sue E. Boyd (ORCID: https://orcid.org/0000-0003-1086-8973)
- Hossay Abas (ORCID: https://orcid.org/0000-0003-2922-1539)
- Peter Blencowe (ORCID: https://orcid.org/0000-0002-3818-7136)
- Hongjie Gao
- Ellen MacDonald (ORCID: https://orcid.org/0009-0006-5245-003X)
- C. Richard Bennett
- Fan Zhang (ORCID: https://orcid.org/0000-0003-0458-6742)
- Emma Stanway
- Chengjun Zhao
Institutions
- Babraham Institute (GB)
- University of Nottingham Ningbo China (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2024-08-09
- DOI
- https://doi.org/10.1021/acs.orglett.4c02615
- Citations
- 2
- Primary Topic
- Marine Sponges and Natural Products
- Type
- article
- Field-Weighted Citation Impact
- 0.77