Synthesis of Non-Natural Amino Acids Based on the Ruthenium-Catalysed Oxidation of a Phenyl Group to Carboxylic Acid

Abstract

An efficient method for the synthesis of enantiopure β-, γ-, and δ-amino acids with proteinogenic side chains, starting from natural α-amino acids, was developed. The method is based on the ruthenium-catalyzed oxidation of a phenyl group to a carboxylic acid. β-Amino acids may be prepared starting from Boc-phenylalaninol. The route described for the synthesis of γ- and δ-amino acids permits the insertion of any chain length between the amino and carboxy functionalities as a result of the original choice of the starting ylide chain length.

Key words

amino acids - amino alcohols - Wittig reaction - oxidations - ruthenium

References

• 1 Willams RH. The Synthesis of Optically Active α-Amino Acids   Pergamon; New York: 1989. 
• 2 Giannis A. Kolter T. Angew. Chem., Int. Ed. Engl.  1993,  32:  1244 
• 3 Duthaler RO. Tetrahedron  1994,  50:  1539 
• 4 Goody RS. Alexandrov K. Engelhard M. ChemBioChem  2002,  3:  399 
• 5 Cheng RP. Gehrtan SH. DeGrado WF. Chem. Rev.  2001,  101:  3219 
• 6 Hanessian S. Luo X. Schaum R. Michnick S. J. Am. Chem. Soc.  1987,  120:  8569 
• 7 Hintermann T. Gademann K. Jaun B. Seebach D. Helv. Chim. Acta  1998,  81:  983 
• 8 Frackenpohl J. Arvidsson PI. Schreiber JV. Seebach D. ChemBioChem  2001,  2:  445 
• 9 Noula C. Loukas V. Kokotos G. Synthesis  2002,  1735 
• 10 Loukas V. Noula C. Kokotos G. J. Peptide Sci.  2003,  9:  312 
• 11a Lee DG. van den Engh M. In Oxidation in Organic Chemistry   Part B:  Trahanovsky WS. Academic Press; New York: 1973.  Chap. 4.
• 11b Courtney JL. In Organic Synthesis by Oxidation with Metal Compounds   Mijs WJ. de Jonge CRHI. Plenum Press; New York: 1986.  Chap. 8. p.445 
• 11c Martin VS. Palazon JM. Rodriguez CM. In Encyclopedia of Reagents for Organic Synthesis   Vol. 6:  Paquette LA. Wiley; Chichester: 1996.  p.4415 
• 12 Naota T. Takaya H. Murahashi SI. Chem. Rev.  1998,  98:  2599 
• 13 Mander LN. Williams CM. Tetrahedron  2003,  59:  1105 
• 14 Carlsen PHJ. Katsuki T. Martin VS. Sharpless KB. J. Org. Chem.  1981,  46:  3936 
• 15 Nunez MT. Martin VS. J. Org. Chem.  1990,  55:  1928 
• 16 Jäger V. Grund H. Bub V. Schwab W. Müller I. Schohe R. Franz R. Ehrler R. Bull. Soc. Chim. Belg.  1983,  92:  1039 
• 17 Georgiadis D. Matziari M. Vassiliou S. Dive V. Yiotakis A. Tetrahedron  1999,  55:  14635 
• 18 Kokotos G. Synthesis  1990,  299 
• 19 Jurczak J. Kobrzycka E. Gruza H. Prokopowicz P. Tetrahedron  1998,  54:  6051 
• 20 Matsuura F. Hamada Y. Shioiri T. Tetrahedron  1993,  49:  8211 
• 21 Norsikian S. Marek I. Klein S. Poisson JF. Normant JF. Chem. Eur. J.  1999,  5:  2055 
• 22 Marini E. Razafindramboa D. Bonato M. Follet M. Synthesis  1992,  1104 
• 23 Travins J. Etzkorn F. J. Org. Chem.  1997,  62:  8387 
• 24 Hunt JCA. Lloyd C. Moody CJ. Slawin AMZ. Takle AK. J. Chem. Soc., Perkin Trans. 1  1999,  3443 
• 25 Gung BW. Zou D. Miyahara Y. Tetrahedron  2000,  56:  9739 
• 26 Smrcina M. Majer P. Majerova E. Guerassina TA. Eissenstat MA. Tetrahedron  1997,  53:  12867