A Concise Synthesis of (2R,6R)-Hydroxynorketamine
Jianfeng Li1, Ankun Zhou2, Xiaoting Wang2
1School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, 1076 Yuhua Road, Chenggong District, Kunming 650500, Yunnan. P. R. of China.
The Journal of Organic Chemistry
|November 1, 2024
Summary
A novel eight-step synthesis of (2R,6R)-hydroxynorketamine was achieved. This efficient method provides a high yield and enantiomeric excess for this important compound.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
Background:
- (2R,6R)-hydroxynorketamine is a significant molecule with potential therapeutic applications.
- Efficient and stereoselective synthesis routes are crucial for accessing such compounds.
Purpose of the Study:
- To develop a concise and efficient eight-step synthesis of (2R,6R)-hydroxynorketamine.
- To utilize key reactions for stereochemical control and high yield.
Main Methods:
- Cerium chloride-enhanced Stork-Danheiser reaction.
- Corey-Bakshi-Shibata asymmetric reduction.
- Overman rearrangement.
- Ruthenium trichloride/sodium periodate-mediated facial selective dihydroxylation.
Main Results:
- Successful synthesis of (2R,6R)-hydroxynorketamine in eight steps.
- Overall yield of 7.3%.
- High enantiomeric excess (ee) of 94.5% achieved.
Conclusions:
- The developed synthetic route is effective for producing (2R,6R)-hydroxynorketamine.
- The combination of advanced synthetic methodologies ensures high stereoselectivity and efficiency.
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