Chinese Journal of Organic Chemistry >
Facile Synthesis of (S)-4-Amino-5-mercaptopentanoic Acid
Received date: 2015-09-05
Revised date: 2015-09-28
Online published: 2015-10-08
Supported by
Project supported by the National Natural Science Foundation of China (No. 81573340) and the “Zhuo Xue” Talent Plan of Fudan University.
(S)-4-Amino-5-mercaptopentanoic acid (glutamate thiol, GluSH) is a derivative of glutamic acid with α-carboxyl group substituted by methanethiol group. Meanwhile, it could be considered as a derivative of cysteine. This amino acid is an important fragment of marine cytotoxic cyclic depsipeptide apratoxin E. Two facile synthetic methods of (S)-4-amino-5-mercaptopentanoic acid are described. For the first strategy, protected D-cysteine derivate was used as starting material. After coupled with Meldrum's acid, the resulting β-keto ester underwent reductive elimination and thermal decarboxylative ring closure to afford 5-substituted pyrrolidinone (γ-lactam). After removal of protecting groups and ring-open, the target compound was obtained in 76.0% overall yield. For the second method, commercial available Boc-Glu(OBzl)-OH was used as starting material. The thiol group was introduced by Mitsunobu reaction after converting the carboxylic acid to its corresponding alcohol. Then the protecting groups of amino, thiol, and carboxylic acid were removed smoothly in one pot to yield (S)-4-amino-5-mercaptopentanoic acid.
Wu Ping , Ma Chunhua , Xu Senhan , Li Yingxia , Zhai Yanjun , Zhang Wei . Facile Synthesis of (S)-4-Amino-5-mercaptopentanoic Acid[J]. Chinese Journal of Organic Chemistry, 2016 , 36(1) : 191 -195 . DOI: 10.6023/cjoc201509005
[1] Wilk, S.; Thlirston, L. S. Neuropeptides 1990, 16, 163.
[2] Claperon, C.; Rozenfeld, R.; Iturrioz, X.; Inguimbert, N.; Okada, M.; Roques, B.; Maigret, B.; Llorens-Cortes, C. Biochem. J. 2008, 416, 37.
[3] Matthew, S.; Schupp, P. J.; Luesch, H. J. Nat. Prod. 2008, 71, 1113.
[4] Chen, Q. Y.; Liu, Y.; Cai, W.; Luesch, H. J. Med. Chem. 2014, 57, 3011.
[5] Comegna, D.; Paola, I.; Saviano, M.; Del Gatto, A.; Zaccaro, L. Org. Lett. 2015, 17, 640.
[6] Bergeron, R. J.; Wiegand, J.; Weimar, W. R.; Vinson, J. R.; Timothy, B.; Jörg, Y.; Guo, Wei.; McManis, J. S. J. Med. Chem. 1999, 42, 95.
[7] Jobron, L.; Hummel, G. Org. Lett. 2000, 2, 2265.
[8] Longobardo, L.; Cecere, N.; DellaGreca, M.; de Paola, I. Amino Acids 2013, 44, 443.
[9] Smrcina, M.; Majer, P.; Majerová, E.; Guerassina, T. A.; Eissenstat, M. A. Tetrahedron 1997, 53, 12867.
[10] Truchot, C.; Wang, Q.; Sasaki, N. A. Eur. J. Org. Chem. 2005, 9, 1765.
/
| 〈 |
|
〉 |
