Wyeth was acquired by Pfizer on October 16, 2009.
WYE-120318, a ring contraction product of methylnaltrexone, and structure revision of coniothyrione
Version of Record online: 8 NOV 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Magnetic Resonance in Chemistry
Volume 50, Issue 12, pages 829–833, December 2012
How to Cite
Kong, F., Zhu, T., Pan, W., Tsao, R., Pagano, T. G., Nguyen, B. and Marquez, B. (2012), WYE-120318, a ring contraction product of methylnaltrexone, and structure revision of coniothyrione. Magn. Reson. Chem., 50: 829–833. doi: 10.1002/mrc.3892
- Issue online: 20 NOV 2012
- Version of Record online: 8 NOV 2012
- Manuscript Accepted: 25 SEP 2012
- Manuscript Revised: 19 SEP 2012
- Manuscript Received: 18 JUL 2012
- ring contraction;
- benzyl-benzilic acid rearrangement
A contracted ring degradation product, WYE-120318 (compound 2), was discovered during the development phase for methylnaltrexone bromide (compound 1) drug substance. The compound was isolated by high-performance liquid chromatography fractionation, and its structure was determined by spectroscopic data analyses. WYE-120318 is formed from methylnaltrexone through a benzyl-benzilic acid type rearrangement reaction to yield an α-hydroxy-cyclopentanecarboxylic acid substructure. The proposed structure and the formation mechanism are confirmed by the synthesis of WYE-120318 from methylnaltrexone (compound 1).
A similar benzyl-benzilic acid type rearrangement reaction can be envisioned as the biological origin of remisporine A (compound 3), a naturally occurring cyclopentadienyl compound that autocatalytically dimerizes to remisporine B (compound 4). The structure of remisporine A was deduced from its dimer 4. Coniothyione (compound 5) can be considered as the first example of a stable natural product bearing the remisporine A skeleton. However, the regiochemistry of the chlorosubstitution in the coniothyrione structure needs to be revised to compound 6 on the basis of the nuclear magnetic resonance data and biogenesis analysis. Copyright © 2012 John Wiley & Sons, Ltd.