Synthesis, Inhaltsverzeichnis Synthesis 2017; 49(06): 1264-1272DOI: 10.1055/s-0036-1588093 paper © Georg Thieme Verlag Stuttgart · New YorkSynthesis of Lacosamide (Vimpat) and Its Derivatives from Aziridine-(2R)-carboxylate Hyeonsu Jeong a Department of Chemistry, Hankuk University of Foreign Studies, Yongin, Kyunggi-Do, 17035, Korea eMail: hjha@hufs.ac.kr , Nagendra Nath Yadav b Department of Chemistry, North Eastern Regional Institute of Science and Technology, Nirjuli, Arunachal Pradesh 791109, India , Hyun-Joon Ha* a Department of Chemistry, Hankuk University of Foreign Studies, Yongin, Kyunggi-Do, 17035, Korea eMail: hjha@hufs.ac.kr› InstitutsangabenArtikel empfehlen Abstract Artikel einzeln kaufen Alle Artikel dieser Rubrik 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. Key words Key words(R)-lacosamide - Vimpat - antiepileptic drug - aziridine - regioselectivity Volltext Referenzen 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 Zusatzmaterial Zusatzmaterial Supporting Information
