RSS-Feed abonnieren
DOI: 10.1055/s-2004-825622
The Synthesis and Characterization of a Novel Insulin Sensitizing Agent
Publikationsverlauf
Publikationsdatum:
08. Juni 2004 (online)
![](https://www.thieme-connect.de/media/synlett/200408/lookinside/thumbnails/10.1055-s-2004-825622-1.jpg)
Abstract
A novel and succinct route to 2-hydroxy-4,6-diarylbenzophenones has been developed through condensation of aryl 1,3-diketones with chalcones. The resultant compounds stimulate insulin-dependent glucose uptake into adipocytes, and improve insulin sensitivity in a rodent model of diabetes.
Key words
cyclizations - diabetes - 2-hydroxybenzophenones - Michael additions - phenols
- 1
Dimroth K.Neubauer G. Chem. Ber. 1959, 92: 2046 - 2
Oganesyan ET.Pyshchev AV.Butenko LI. Pharm. Chem. J. 1999, 33 (9): 480 - 3
Ivanov Kh.Tcholakova Ts. Synthesis 1981, 392 - 4
Murray WV.Wachter MP. J. Org. Chem. 1990, 55: 3424
References
Experimental Procedure for the Conversion of 6 to 1: Diketoacid 6 (7.8 g, 33 mmol) is combined with trans-chalcone (6.25 g, 30 mmol) in 125 mL of EtOH. Piperidine (20 mL) is added, and the resultant solution is heated at 100 °C for 16 h. The volatiles are removed in vacuo; the residue is taken up in 600 mL of 0.1 N aq NaOH and extracted once with 100 mL of Et2O. The aqueous phase is acidified to pH 3 with 1 N H3PO4 and extracted with two 150 mL portions of EtOAc. These organic extracts are washed with brine, dried over Na2SO4, filtered through Celite and concentrated to give 7 as a semisolid. Crude 7 is dissolved in 250 mL of CHCl3; a solution of 1.6 mL of bromine (1 equiv) in 10 mL of CHCl3 is added dropwise over 5 min, and the resultant solution is allowed to stir at ambient temperature for 1 h. The volatiles are removed in vacuo; residual bromine is chased with CHCl3. The residue is dissolved in 250 mL of CHCl3 and cooled to -20 °C; 8 mL of DBU is added dropwise, and the resultant solution is warmed to ambient temperature and stirred for 15 h. The volatiles are removed in vacuo; the residue is taken up in 600 mL of 0.1 N aq NaOH and stirred for 3 h with 100 mL of Et2O. The ether extract is removed; the aqueous phase is acidified to pH 3 with 1 N H3PO4 and extracted with two 150 mL portions of EtOAc. These organic extracts are washed with brine, dried over Na2SO4, and filtered through Celite. Reduction in volume to ca. 75 mL provides a solid, which is collected by filtration to give 3.4 g (27% yield) of 1. Further concentration of the mother liquors provides a second crop of solid 1 (0.9g, 7%).
6Analytical data for compound 1: 1H NMR (DMSO, 400 MHz): δ = 7.67 (d, 2 H, J = 7.4 Hz), 7.54 (t, 1 H, J = 7.4 Hz), 7.40-7.50 (m, 10 H), 7.15-7.20 (m, 4 H), 6.77 (s, 1 H), 2.83 (m, 2 H), 2.38 (m, 2 H). 13C NMR (DMSO, 100 MHz):
δ = 197.0, 174.0, 152.6, 143.9, 140.7, 139.5, 138.1, 137.7, 133.1, 128.9, 128.8, 128.5, 128.2, 128.1, 127.4, 127.3, 127.1, 126.9, 126.0, 123.0, 33.5, 22.1. MS (ESI+): m/z = 405, 423, 445. MS (ESI-): m/z = 421.