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Synthesis 2014; 46(22): 3047-3058
DOI: 10.1055/s-0034-1378653
DOI: 10.1055/s-0034-1378653
paper
A Practical Synthesis of a Potent and Selective Diacylglycerol Acyltransferase-1 (DGAT-1) Inhibitor
Weitere Informationen
Publikationsverlauf
Received: 12. Juni 2014
Accepted: 21. Juli 2014
Publikationsdatum:
25. August 2014 (online)
Abstract
A practical synthesis of a potent, selective, and orally efficacious diacylglycerol acyltransferase-1 (DGAT-1) inhibitor, is described. This synthesis is suitable for multi-kilogram scale with high regioselectivity and stereoselectivity. The synthesis involves a Knoevenagel condensation with Meldrum’s acid followed by the stereoselective addition of phenyl cuprate, regioselective Friedel–Crafts acylation, cyclization, and a regioselective reduction through an enol triflate with catalytic platinum oxide to provide the desired compound in 5.2% yield over 12 steps.
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References
- 1 Cases S, Smith SJ, Zheng Y.-W, Myers HM, Lear SR, Sande E, Novak S, Collins C, Welch CB, Lusis AJ, Erickson SK, Farese RV. Jr. Proc. Natl. Acad. Sci. U.S.A. 1998; 95: 13018
- 2a Bell RM, Coleman RA. Ann. Rev. Biochem. 1980; 49: 459
- 2b Lehner R, Kuksis A. Prog. Lipid Res. 1996; 35: 169
- 2c Dow RL. RSC Drug Discovery Ser. 2012; 27: 215
- 2d Cases S, Stone SJ, Zhou P, Yen E, Tow B, Lardizabal KD, Voelker T, Farese RV. Jr. J. Biol. Chem. 2001; 276: 38870
- 3a Hubbard BK, Enyedy I, Gilmore TA, Serrano-Wu MH. Expert Opin. Ther. Pat. 2007; 17: 1331
- 3b Zammit VA, Buckett LK, Turnbull AV, Wure H, Proven A. Pharmacol. Ther. 2008; 118: 295
- 4a Birch AM, Buckett LK, Turnbull AV. Curr. Opin. Drug Discovery Dev. 2010; 13: 489
- 4b Chen Hubert C, Farese Robert VJr. Arterioscl. Thromb. Vasc. Biol. 2005; 25: 482
- 4c King AJ, Judd AS, Souers AJ. Expert Opin. Ther. Pat. 2010; 20: 19
- 5a Fox BM, Furukawa N, Hao X, Iio K, Inaba T, Jackson SM, Kayser F, Labelle M, Li K, Matsui T, McMinn DL, Ogawa N, Rubenstein SM, Sagawa S, Sugimoto K, Suzuki M, Tanaka M, Ye G, Yoshida A, Zhang J. Patent WO2004047755 A2, 20031121, 2004
- 5b Fox BM, Sugimoto K, Iio K, Yoshida A, Zhang J, Li K, Hao X, Labelle M, Smith M.-L, Rubenstein SM, Ye G, McMinn D, Jackson S, Choi R, Shan B, Ma J, Miao S, Matsui T, Ogawa N, Suzuki M, Kobayashi A, Ozeki H, Okuma C, Ishii Y, Tomimoto D, Furakawa N, Tanaka M, Matsushita M, Takahashi M, Inaba T, Sagawa S, Kayser F. J. Med. Chem. 2014; 57: 3464
- 6 Li K, Fox BM, Zhang J, Iio K, Suzuki M, Soichiro I, Ozeki H, Kobayashi A, Ma J, Hao A, Labelle M, McMinn D, Smith M, Sagawa S, Furukawa N, Inaba T, Matsushita M, Matsui T, Ogawa N, Okuma C, Sugimoto K, Tanaka M, Yoshida A, Ishii Y, Tomimoto D, Jackson S, Choi R, Shan B, Srivastava A, Kayser F. Abstracts of Papers, 245th ACS National Meeting & Exposition, New Orleans, April 7–11, 2013. American Chemical Society; Washington DC: 2013: MEDI-410
- 7 Davis AP, Egan TJ, Orchard MG, Cunningham D, McArdle P. Tetrahedron 1992; 48: 8725
- 8a Yadav GC, Dorwal HN, Valavala S, Sharma VK. Patent WO 2007138435 A2, 20070524, 2007
- 8b Kirsch P, Tarumi K. Angew. Chem. Int. Ed. 1998; 37: 484
- 8c Marvell EN, Sturmer D, Rowell C. Tetrahedron 1966; 22: 861
- 9 Jones G. Org. React. 1967; 15: 204
-
10 Castro J, Moyano A, Pericas MA, Riera A, Greene AE, Alvarez-Larena A, Piniella JF. J. Org. Chem. 1996; 61: 9016
- 11 Haslego ML, Smith FX. Synth. Commun. 1980; 10: 421
- 12 Lipshutz BH, Sengupta S. Org. React. 1992; 41: 135
- 13 Layer RW, MacGregor IR. J. Org. Chem. 1956; 21: 1120