An Efficient Method for the Synthesis of Enantiopure ω-Amino Acids with Proteinogenic Side Chains

Abstract

An efficient method for the synthesis of enantiopure ω-amino acids with proteinogenic side chains, starting from the corresponding natural α-amino acids, was developed. N-Protected amino aldehydes, obtained from the corresponding amino alcohols by oxidation with NaOCl in the presence of 4-acetamido-2,2,6,6-tetra­methylpiperidine-1-yloxy free radical (AcNH-TEMPO), reacted with the ylides generated from TrO(CH₂)_nP⁺Ph₃I^-. Catalytic hydrogenation produced N-protected ω-amino alcohols. Boc-Protected ω-amino acids were obtained in high yields by the oxidation of these alcohols using NaOCl in the presence of a catalytic amount of AcNH-TEMPO and Bu₄N⁺HSO₄ ^-. The present route to ω-amino acids permits the insertion of any chain length between the amino and carboxy functionalities depending on the chain length of the starting ylide used for the Wittig olefination reaction.

Key words

amino acids - amino alcohols - amino aldehydes - Wittig reactions - ylides

References

• 1a Giannis A. Kolter T. Angew. Chem., Int. Ed. Engl.  1993,  32:  1244 
• 1b Gante J. Angew. Chem., Int. Ed. Engl.  1994,  33:  1699 
• 1c Kokotos G. Martin V. Constantinou-Kokotou V. Gibbons WA. Amino Acids  1996,  11:  329 
• 2a Williams RH. In The Synthesis of Optically Active α-Amino Acids   Pergamon; New York: 1989. 
• 2b Duthaler RO. Tetrahedron  1994,  50:  1539 
• 2c Rutjes FPJT. Wolf LB. Schoemaker HE. J. Chem. Soc., Perkin Trans. 1  2000,  4197 
• 3 Seebach D. Matthews JL. Chem. Commun.  1997,  2015 
• 4 Hintermann T. Gademann K. Jaun B. Seebach D. Helv. Chim. Acta  1998,  81:  983 
• 5 Gellman SH. Acc. Chem. Res.  1998,  31:  173 
• 6 Hanessian S. Yang H. Schaum R. J. Am. Chem. Soc.  1996,  118:  2507 
• 7 Hanessian S. Luo X. Schaum R. Michnick S. J. Am. Chem. Soc.  1998,  120:  8569 
• 8 Frackenpohl J. Arvidsson PI. Schreiber JV. Seebach D. ChemBioChem  2001,  2:  445 
• 9a Juaristi E. Enantioselective Synthesis of β-Amino Acids   Wiley-VCH; New York: 1997. 
• 9b Juaristy E. Lopez-Ruiz H. Curr. Med. Chem.  1999,  6:  983 
• 10 El Marini A. Roumenstat ML. Viallefont P. Razafindramboa D. Bonato M. Follet M. Synthesis  1992,  1104 
• 11 Hanessian S. Schaum R. Tetrahedron Lett.  1997,  38:  163 
• 12 Smrcina M. Majer P. Majerová E. Guerassina TA. Eissenstat MA. Tetrahedron  1997,  53:  12867 
• 13 Kokotos G. Synthesis  1990,  299 
• 14 Kokotos G. Noula C. J. Org. Chem.  1996,  61:  6994 
• 15 Jurczak J. Golebiowski A. Chem. Rev.  1989,  89:  149 
• 16 Kokotos G. Markidis T. Constantinou-Kokotou V. Synthesis  1996,  1223 
• 17 Falkiewicz B. Koodziejczyk AS. Liberek B. Winiewski K. Tetrahedron  2001,  57:  7909 
• 18 Walfred SS. Thorsten EF. Synthesis  1990,  453 
• 19 Franciotti M. Mordini A. Taddei M. Synlett  1992,  137 
• 20 Jurczak J. Kobrzycka E. Gruza H. Prokopowicz P. Tetrahedron  1998,  54:  6051 
• 21a Leanna MR. Sowin TJ. Morton HE. Tetrahedron Lett.  1992,  33:  5029 
• 21b Ma Z. Bobbitt JM. J. Org. Chem.  1991,  56:  6110 
• 22 Maryanoff BE. Reitz AB. Duhl-Emswiler BA. J. Am. Chem. Soc.  1985,  107:  217 
• 23a Leznoff CC. Wong JY. Can. J. Chem.  1972,  50:  2892 
• 23b Kaats-Richters VEM. Zwikker JM. Keegstra EMD. Jenneskens LW. Synth. Commun.  1994,  24:  2399 
• 24a Schlosser M. Schaub B. de Oliveira-Neto J. Jeganathan S. Chimia  1986,  40:  244 
• 24b Maryanoff BE. Reitz AB. Chem. Rev.  1989,  89:  863 
• 25 Marcovici-Mizrahi D. Gottlieb HE. Marks V. Nudelman A. J. Org. Chem.  1996,  61:  8402 
• 26 Dale JA. Dull DL. Mosher H. J. Org. Chem.  1969,  34:  2543