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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Formal synthesis of (±)-morphine.
Jing Li1, Guo-Liang Liu, Xian-He Zhao
1State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, 222 Tianshui Nanlu, Lanzhou 730000, China.
Chemistry, an Asian Journal
|March 20, 2013
Summary
Researchers developed a new synthetic strategy for creating morphine rings B and E. Key steps included samarium(II) iodide-promoted coupling and tandem reactions for assembling crucial molecular bonds.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Medicinal Chemistry
Background:
- Morphine is a vital opiate analgesic with a complex pentacyclic structure.
- Existing synthetic routes to morphine and its analogs are often lengthy and inefficient.
- Developing novel strategies for morphine synthesis is crucial for accessing new pain therapeutics.
Purpose of the Study:
- To develop a novel and efficient synthetic strategy for constructing morphine rings B and E.
- To establish key bond-forming reactions for the assembly of the morphine core structure.
- To explore enantioselective synthesis of morphine.
Main Methods:
- Development of a synthetic route employing samarium(II) iodide (SmI2)-promoted reductive coupling/desulfurization.
- Utilizing a tandem alcoholysis/oxa-Michael addition sequence for key bond formations.
- Investigating asymmetric tandem alcoholysis/oxa-Michael addition for enantiocontrol.
Main Results:
- Successful construction of morphine rings B and E via a novel synthetic pathway.
- Efficient assembly of the C9-C14 and C5-O bonds using SmI2-promoted and tandem reactions.
- Demonstration of enantioselective synthesis of morphine through asymmetric tandem reactions.
Conclusions:
- A novel synthetic strategy for morphine ring construction has been established.
- The developed method offers an efficient approach to the morphine core, potentially aiding in the synthesis of new analgesics.
- The feasibility of enantioselective synthesis opens avenues for producing specific morphine enantiomers.
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