α-Methyl and β,β-dimethyl amino acids

Published on 09.02.2017

α-Methyl and alkyl-amino acids can be produced by a number of platforms, where the (2S,4S)-4-methyl-2-phenyloxazolidin-5-one scaffold is one of the most popular one.

α-Methyl and alkyl-amino acids can be produced by a number of platforms, where the (2S,4S)-4-methyl-2-phenyloxazolidin-5-one scaffold is one of the most popular one. We optimize published procedures and have own proprietary ones, which enable us to supply all kinds of protected α-methyl amino acids.

Such building blocks are being used to build up resistance towards proteolytic digestion of corresponding peptides or to implement certain amid bind conformation.

An alternative are β,β-dimethylated amino acids, where structure of the α-carbon is being maintained and the stability providing property comes through derivatization at the neighbouring carbon.

With tert-leucine and penicillamine there are already derivatives known in the peptide community, however, access to other analogues is very unique and available only through our specific synthesis platform.

References:

Synthesis and Biological Activity of Analogues of the Antimicrotubule Agent N,beta,beta-Trimethyl-L-phenylalanyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide (HTI-286); A. Zask, G. Birnberg, K. Cheung, J. Kaplan, C. Niu, E. Norton, R. Suayan, A. Yamashita, D. Cole, Z. Tang, G. Krishnamurthy, R. Williamson, G. Khafizova, S. Musto, R. Hernandez, T. Annable, X. Yang, C. Discafani, C. Beyer, L.M. Greenberger, F. Loganzo, S. Ayral-Kaloustian; J. Med. Chem. 2004; 47: 4774-4786.
Serine as Chiral Educt for the Practical Synthesis of Enantiopure N-Protected beta-Hydroxyvaline; J.E. Dettwiler, W.D. Lubell; J. Org. Chem. 2003; 68: 177-179.
Total synthesis of the large non-ribosomal peptide polytheonamide B; M. Inoue, N. Shinohara, S. Tanabe, T. Takahashi, K. Okura, H. Itoh, Y. Mizoguchi, M. Iida, N. Lee; S. Matsuoka; Nature Chemistry 2010; 2: 280-285. doi:10.1038/nchem.554
Synthesis of beta,beta-Dimethylated Amino Acid Building Blocks Utilizing the 9-Phenylfluorenyl Protecting Group; N. Kawahata, M. Weisberg, M. Goodman; J. Org. Chem. 1999; 64: 4362-4369.
A General Method for Making Peptide Therapeutics Resistant to Serine Protease Degradation: Application to Dipeptidyl Peptidase IV Substrates; K.R. Heard, W. Wu, Y. Li, P. Zhao, I. Woznica, J.H. Lai, M. Beinborn, D.G. Sanford, M.T. Dimare, A.K. Chiluwal, D.E. Peters, D. Whicher, J.L. Sudmeier, W.W. Bachovchin; J. Med. Chem. 2013; 56: 8339−8351; dx.doi.org/10.1021/jm400423p.