Stereoselective Synthesis of Linustedastat Via Deoxy-Aromatization Strategy
Abstract An efficient and stereoselective synthesis of Linustedastat (1) is reported, commencing from inexpensive and commercially available sitolactone. The route features a highly chemoselective Grignard addition, followed by sequential double aldol condensations to construct the core steroidal framework. A key step involves a novel deoxy-aromatization of a fluorinated steroid intermediate, setting the stage for a stereoselective hydrogenation and a 1,4-conjugate addition to further elaborate the molecule. This strategically designed sequence delivers the complex and electron-deficient fluorinated steroidal architecture in 16 steps with an 11.0% overall yield.
Authors
- Chengfeng Ye (ORCID: https://orcid.org/0000-0002-9529-3410)
- Leleti Rajender Reddy (ORCID: https://orcid.org/0000-0001-9182-2277)
- Chris H. Senanayake (ORCID: https://orcid.org/0009-0009-3170-0687)
- Mohammed Sharique (ORCID: https://orcid.org/0000-0002-4528-4807)
- Anji Chen (ORCID: https://orcid.org/0000-0002-8943-9663)
- Madhusudhan Reddy Gadi (ORCID: https://orcid.org/0000-0003-3668-4646)
- Praveen Kumar Gajula (ORCID: https://orcid.org/0009-0008-5051-4612)
- Jonathan M. Bietsch
- Manasa Mamunooru
- Leena Hirvelä
- Santhosh Reddy Naini (ORCID: https://orcid.org/0000-0001-7825-5810)
- Xueyi Zhang (ORCID: https://orcid.org/0000-0002-3790-5116)
- Bo Qu (ORCID: https://orcid.org/0000-0001-7347-0108)
- Rahul D. Shingare (ORCID: https://orcid.org/0000-0002-8690-2229)
- Nageswara Rao Kalikinidi (ORCID: https://orcid.org/0000-0002-5378-9207)
- Zhirui Wang
- Luis Sierra
- Jiezhen Li
- Huiping Zhao
- Tony Hudgens
Publication Details
- Journal
- Organic Letters
- Published
- 2026-10-14
- DOI
- https://doi.org/10.1021/acs.orglett.6c03795
- Primary Topic
- Steroid Chemistry and Biochemistry
- Type
- article
- Field-Weighted Citation Impact
- 0.00