A variation of Mattox rearrangement mechanism under alkaline condition

Tetrahedron Letters

Volumn 48, Issue 22, 2007, Pages 3901-3905

  Li, Min ^a   Chen, Bin ^a   Lin, Mingxiang ^a   Chan, Tze Ming ^a   Fu, Xiaoyong ^a   Rustum, Abu ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Betamethasone dipropionate; Betamethasone enol aldehyde; Corticosteroids; Degradation; Mattox rearrangement

Indexed keywords

1,3 DIHYDROXYACETONE; ACETONE; CORTICOSTEROID DERIVATIVE; UNCLASSIFIED DRUG;

ACIDIFICATION; ALKALINITY; ARTICLE; CHEMICAL STRUCTURE;

EID: 34247612406     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2007.03.127     Document Type: Article

References (10)

1. Mattox V.R. J. Am. Chem. Soc. 74 (1952) 4340-4347
2. Weiss G., Monder C., and Bradlow L. J. Clin. Endocrinol. Metab. 43 (1976) 696-699
3. Lewbart M.L., and Mattox V.R. J. Org. Chem. 29 (1964) 513-521
4. You Z., Khalil M.A., Ko D.-H., and Lee H.J. Tetrahedron Lett. 36 (1995) 3303-3306
5. Herzog H.L., Gentles M.J., Marshall H., and Hershberg E.B. J. Am. Chem. Soc. 83 (1961) 4073-4076
6. Lewbart M.L., Monder C., Boyko W.J., Singer C.J., and Iohan F. J. Org. Chem. 54 (1989) 1332-1338
7. Singer C.J., Iohan F., and Monder C. Endocrinolgy 119 (1986) 1356-1361
8. n analyses. The HPLC system was equipped with a Supercosil ABZ-Plus C18, 250 × 4.6 mm, 5 μm column. Isocratic elution was effected with a mobile phase of acetonitrile/10 mM ammonium acetate (1/1, v/v) at a flow rate of 2 mL/min. The HPLC flow was split at a ratio of 10:1 prior to entering the MS detector; approximately 200 μL/min of the HPLC flow was directed into the ion source of the MS detector. Positive electron spray ionization was used with a spray voltage of 4.5 kV. The capillary temperature was set at 300 °C and the sheath gas flow rate 40 units. A full MS scan was obtained in the mass range of 100-800 Da. Tandem MS/MS experiments were performed using helium as the collision gas with an isolation width of 3.0 Da for the parent ion and normalized collision energy of 28.
9. 13C NMR; the results and assignment are summarized in Table 1. Various 2D experiments were performed to establish the structural connectivity and configurations.
10. The acidic stress conditions used in these experiments to generate the enol aldehyde from betamethasone and its derivatives are described in the legend of Figure 3.