pH-dependent, stereoselective dimerization of sinomenine.

Abstract

In a continuing study on discovery of more potent derivatives of sinomenine (1), a clinically available alkaloid for rheumatoid arthritis (RA) treatment, oxidation of sinomenine provided two unique stereoisomers, disinomenines 2 and 3. The structure of 3 was determined by MS, NMR, and X-ray analysis. The formation of 2 and 3 via oxidation of sinomenine by potassium permanganate (KMnO4) exhibited a pH-dependent stereoselectivity. The bioassay results using human synovial sarcoma cells (SW982) showed that 2 inhibited, while 3 stimulated, IL-6 production.

• Authors: Zhang-Shuang Deng, Yu Zhao, Cui-Cui He, Jie Jin, Yun-Mian He, Jian-Xin Li
• Journal: Organic letters (Org Lett) Vol. 10 Issue 17 Pg. 3879-82 (Sep 04 2008) ISSN: 1523-7052 [Electronic] United States
• PMID: 18646768 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Morphinans
• sinomenine

Topics

• Cell Line, Tumor
• Crystallography, X-Ray
• Dimerization
• Humans
• Hydrogen-Ion Concentration
• Interleukin-6 (antagonists & inhibitors, biosynthesis)
• Morphinans (chemical synthesis, chemistry, pharmacology)
• Oxidation-Reduction
• Sarcoma, Synovial (metabolism)
• Stereoisomerism