Total Synthesis of Tipranavir Based on Iridium-Catalyzed Asymmetric Allylic Substitution of Dihydropyranone
An efficient and highly enantioselective synthesis of tipranavir is realized based on an iridium-catalyzed asymmetric allylic substitution. High yield and diastereoselectivity (>20:1), as well as excellent enantioselectivity (99% <i>ee</i>), were obtained for the key intermediate through direct asymmetric alkylation reaction of dihydropyranone with allylic <i>tert</i>-butyl carbonate. Anti-AIDS drug of tipranavir was finally accomplished in 8 steps and 6 pots starting from commercially available 1-phenyl-3-hexanone in 20.7% overall yield with 99% <i>ee</i> and >20:1 <i>dr</i>.
Authors
- Xiaofei Zeng (ORCID: https://orcid.org/0000-0003-4222-1365)
- Wenhao Gan
- Xiaoyu Han (ORCID: https://orcid.org/0000-0002-0855-0563)
- Yixin Lü (ORCID: https://orcid.org/0000-0002-5730-166X)
- Yongjiang Wang (ORCID: https://orcid.org/0000-0003-2155-5577)
- Min Yu (ORCID: https://orcid.org/0009-0008-2955-7677)
- Minghui He (ORCID: https://orcid.org/0000-0001-7957-854X)
- Ziqiang Dai
- Yakang Huang
Institutions
- Hangzhou Normal University (CN)
- National University of Singapore (SG)
- Zhejiang University of Science and Technology (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2024-11-19
- DOI
- https://doi.org/10.1021/acs.orglett.4c03736
- Citations
- 2
- Primary Topic
- HIV/AIDS drug development and treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.78
Funders
- National Natural Science Foundation of China
- Basic Public Welfare Research Program of Zhejiang Province