Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml
Synthesis 2017; 49(06): 1264-1272
DOI: 10.1055/s-0036-1588093
DOI: 10.1055/s-0036-1588093
paper
Synthesis of Lacosamide (Vimpat) and Its Derivatives from Aziridine-(2R)-carboxylate
Further Information
Publication History
Received: 08 September 2016
Accepted after revision: 21 October 2016
Publication Date:
23 November 2016 (online)
Abstract
An efficient and scalable synthesis of the antiepileptic drug (R)-lacosamide and its derivatives has been achieved from commercially available aziridine-(2R)-carboxylate in three simple sequential steps, including regioselective aziridine ring opening, debenzylation followed by acetylation in one pot, and amide formation. The advantage of this protocol is that the starting material and reagents are commercially available and a single purification by recrystallization is required after all the chemical transformations, providing the final drug in >99.9% ee.
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0036-1588093.
- Supporting Information
-
References
- 1a Choi D, Stables JP, Kohn H. J. Med. Chem. 1996; 39: 1907
- 1b Morieux P, Stables JP, Kohn H. Bioorg. Med. Chem. 2008; 16: 8968
- 1c Wang Y, Park KD, Salome C, Wilson SM, Stables JP, Liu R, Khanna R, Kohn H. ACS Chem. Neurosci. 2011; 2: 90
- 2a Krauss G, Ben-Menachem E, Mameniskiene R, Vaiciene-Magistris N, Brock M, Whitesides JG, Johnson ME. Epilepsia 2010; 51: 951
- 2b Brandt C, Heile A, Potschka H, Stoehr T, Loscher W. Epilepsia 2006; 47: 1803
- 2c Simoens S. Curr. Med. Res. Opin. 2011; 27: 1329
- 2d McCleane G. Expert Opin. Invest. Drugs 2010; 19: 1129
- 3a Cross SA, Curran MP. Drugs 2009; 69: 449
- 3b Sridharan R, Murthy BN. Epilepsia 1999; 40: 631
- 3c Duncan JS, Sander JW, Sisodia SM, Walker MC. Lancet 2006; 367: 1087
- 4a Andurkar SV, Stables JP, Kohn H. Tetrahedron: Asymmetry 1998; 9: 3841
- 4b Park KD, Stables JP, Liu R, Kohn H. Org. Biomol. Chem. 2010; 8: 2803
- 5a Stecko S. J. Org. Chem. 2014; 79: 6342
- 5b Wadavrao SB, Narikimalli A, Narsaiah AV. Synthesis 2013; 45: 3383
- 5c Garg Y, Pandey SK. J. Org. Chem. 2015; 80: 4201
- 5d Muthukrishnan M, Mujahid M, Sasikumar M, Mujumdar P. Tetrahedron: Asymmetry 2011; 22: 1353
- 5e Wehlan H, Oehme J, Schäfer A, Rossen K. Org. Process Res. Dev. 2015; 19: 1980
- 6a Eum H, Choi J, Cho CG, Ha HJ. Asian J. Org. Chem. 2015; 4: 1399
- 6b Jung JH, Yoon DH, Lee K, Shin H, Lee WK, Yook CM, Ha HJ. Org. Biomol. Chem. 2015; 13: 8187
- 6c Choi J, Ha HJ. J. Korean Chem. Soc. 2015; 59: 203
- 6d Ha HJ, Jung JH, Lee WK. Asian J. Org. Chem. 2014; 3: 1020
- 6e Yoon D.-H, Kang P, Lee WK, Kim Y, Ha HJ. Org. Lett. 2012; 14: 429
- 7a Stankovic S, D’hooghe M, Catak S, Eum H, Waroquier M, Van Speybroeck V, De Kimpe N, Ha HJ. Chem. Soc. Rev. 2012; 41: 643
- 7b Lee KM, Kim JC, Kang P, Lee WK, Eum H, Ha H.-J. Tetrahedron 2012; 68: 883
- 7c Singh A, Kim B, Lee WK, Ha HJ. Org. Biomol. Chem. 2011; 9: 1372
- 7d Kim Y, Ha H.-J, Yun SY, Lee WK. Chem. Commun. 2008; 4363
- 7e Yoon HJ, Kim Y.-W, Lee BK, Lee WK, Kim Y, Ha H.-J. Chem. Commun. 2007; 79
- 8 Yook CM, Eum H, Ha HJ, Kang KY, Lee WK. Bull. Korean Chem. Soc. 2011; 32: 2879
- 9 Lee WK, Ha HJ. Aldrichimica Acta 2003; 36: 57
- 10 Han SM, Ma SH, Ha HJ, Lee WK. Tetrahedron 2008; 64: 11110
- 11a Hwang GI, Chung JH, Lee WK. J. Org. Chem. 1996; 61: 6183
- 11b Choi SK, Lee JS, Kim JH, Lee WK. J. Org. Chem. 1997; 62: 743
- 12a Yadav NN, Choi J, Ha HJ. Org. Biomol. Chem. 2016; 14: 6426
- 12b Hanessian S, Chenard E, Guesne S, Cusson JP. J. Org. Chem. 2014; 79: 9531
- 13a Park KD, Yang XF, Lee H, Dustrude ET, Wang Y, Khanna R, Kohn H. ACS Chem. Neurosci. 2013; 4: 463
- 13b Salomé C, Salomé-Grosjean E, Park KD, Morieux P, Swendiman R, DeMarco E, Stables JP, Kohn H. J. Med. Chem. 2009; 53: 1288
- 13c Park KD, Yang XF, Dustrude ET, Wang Y, Ripsch MS, White FA, Khanna R, Kohn H. ACS Chem. Neurosci. 2015; 6: 316
- 13d King AM, Salomé C, Salomé-Grosjean E, De Ryck M, Kaminski R, Valade A, Stables JP, Kohn H. J. Med. Chem. 2011; 54: 6417