Synthesis 2014; 46(07): 967-971
DOI: 10.1055/s-0033-1340816
paper
© Georg Thieme Verlag Stuttgart · New York

Domino 1,3-Dipolar Cycloadditions of N-Alkyl-α-Amino Esters with Paraformaldehyde: A Direct Access to α-Hydroxymethyl α-Amino Acids

Luis M. Castelló
Departamento de Química Orgánica e Instituto de Síntesis Orgánica (ISO), Facultad de Ciencias, Universidad de Alicante, 03080 Alicante, Spain   Fax: +34(96)5903549   eMail: cnajera@ua.es   eMail: jmsansano@ua.es
,
Carmen Nájera*
Departamento de Química Orgánica e Instituto de Síntesis Orgánica (ISO), Facultad de Ciencias, Universidad de Alicante, 03080 Alicante, Spain   Fax: +34(96)5903549   eMail: cnajera@ua.es   eMail: jmsansano@ua.es
,
José M. Sansano*
Departamento de Química Orgánica e Instituto de Síntesis Orgánica (ISO), Facultad de Ciencias, Universidad de Alicante, 03080 Alicante, Spain   Fax: +34(96)5903549   eMail: cnajera@ua.es   eMail: jmsansano@ua.es
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 04. Dezember 2013

Accepted after revision: 22. Januar 2014

Publikationsdatum:
11. Februar 2014 (online)


Abstract

N-Alkyl-α-amino esters undergo a domino reaction, based on the iminium cation generation, with paraformaldehyde, followed by a 1,3-dipolar cycloaddition of the stabilized azometh­ine ylide with another equivalent of formaldehyde. The resulting products are oxazolidines, which can be transformed after hydrolysis into α-hydroxymethyl α-amino acid or its derivatives. The diastereoselective 1,3-dipolar cycloaddition was performed using sarcosine (–)-menthyl or (–)-8-phenylmenthyl esters affording the cyclic product with moderate enantiomeric ratio.

Supporting Information

 
  • References

    • 1a Sirin GS, Zhou Y, Lior-Hoffmann L, Wang S, Zhang Y. J. Phys. Chem. B 2012;  116:  12199
    • 1b Halliday AC, Greenfield SA. Protein Pept. Lett. 2012;  19:  165
  • 2 Mijakovic I, Macek B. Microbiol. Rev. 2012; 36: 877
  • 3 Yehezkel G, Cohen L, Kliger A, Manor E, Khalaila I. J. Biol. Chem. 2012; 287: 28755
    • 4a Walsh G. Biopharmaceuticals: Biochemistry and Biotechnology. Wiley; Chichester: 2003
    • 4b Delivery Technologies for Biopharmaceuticals: Peptides, Proteins, Nucleic Acids and Vaccines. Jorgensen L, Nielson HM. Wiley; Chichester: 2009
  • 5 Wolosker H. Biochim. Biophys. Acta 2011; 1814: 1558
  • 6 Sacchi S, Caldinelli L, Cappelletti P, Pollegioni L, Molla G. Amino Acids 2012; 43: 1833
  • 7 Nakano K, Kotsuki H, Ichikawa Y. Org. Prep. Proced. Int. 2008; 40: 67
  • 8 Meyer SG. E, Wendt AE, Scherer M, Liebisch G, Kerkweg U, Schmitz G, de Groot H. Arch. Biochem. Biophys. 2012; 526: 60
  • 9 Byun H.-S, Lu X, Bittman R. Synthesis 2006; 2447

    • For examples of general synthesis of α-amino acids, see:
    • 10a Duthaler RO. Tetrahedron 1994; 50: 1539
    • 10b Nájera C, Sansano JM. Chem. Rev. 2007; 107: 4273
    • 10c Asymmetric Synthesis and Application of α-Amino Acids, ACS Symposium Series 1009. Soloshonok VA, Izawa K. American Chemical Society; New York: 2009
    • 10d Saladino R, Botta G, Crucianelli M. Rev. Med. Chem. 2012; 12: 277

      For reviews, see:
    • 11a Nájera C, Sansano JM. Curr. Org. Chem. 2003; 7: 1105
    • 11b Hashimoto T, Maruoka K. Handbook of Cyclization Reactions . Ma S. Wiley-VCH; Weinheim: 2010
    • 12a Izquierdo M, Osuna S, Filippone S, Martin-Domenech A, Sola M, Martin N. J. Org. Chem. 2009; 74: 6253
    • 12b Cioffi CT, Palkar A, Melin F, Kumbhar A, Echegoyen L, Melle-Franco M, Zerbetto F, Rahman GM, Ehli C, Sgobba V, Guldi DM. A, Prato M. Chem. Eur. J. 2009; 15: 4419
    • 12c Milic D, Prato M. Eur. J. Org. Chem. 2010; 476
    • 13a Chinchilla R, Falvello LR, Galindo N, Nájera C. Eur. J. Org. Chem. 2001; 3133
    • 13b Aldous DJ, Hamelin EM.-N, Harwood LM, Thurairatnam S. Synlett 2001; 1841
    • 13c Begue J.-P, Bonnet-Delpon D, Chennoufi A, Ourevitch M, Ravikumar KS, Rock MH. J. Fluorine Chem. 2001;  107:  275
    • 13d Cardoso AL, Kaczor A, Silva AM. S, Fausto R, Pinho e Melo TM. V. D, Rocha Gonsalves A M. d’A. Tetrahedron 2006; 62: 9861
  • 14 The synthetic approach to threo-2-amino-3-hydroxy esters possessing long alkyl chains was performed from chiral azomethine ylides by reaction of (5R)-5-phenylmorpholin-2-one with long-chain aldehydes. In the presence of a second equiv of aldehydes, the azomethine ylide can be trapped: Brome VA, Harwood LM, Osborn HM. I. Can. J. Chem. 2006; 84: 1448

    • The 1,3-DC of metallo-azomethine ylides derived from benzaldehyde imines and benzophenone imines was previously published:
    • 15a Seashore-Ludlow B, Torssell S, Somfai P. Eur. J. Org. Chem. 2010; 3927
    • 15b Seashore-Ludlow B, Villo P, Somfai P. Chem. Eur. J. 2012; 18: 7219
  • 16 Pineiro M, Pinho e Melo TM. V. D. Eur. J. Org. Chem. 2009; 5287
  • 17 Cativiela C, Ordóñez M. Tetrahedron: Asymmetry 2009; 20: 1
  • 18 For a recent example of the 1,3-DC using naturally occurring (–)-menthol as chiral auxiliary, see: Bonini BF, Boschi F, Franchini MC, Fochi M.-F, Fini F, Mazzanti A, Ricci A. Synlett 2006; 543
  • 19 Chiral oxazolidine acetates derived from (–)-8-phenyl-menthol have been employed in 1,3-DC using a different method: Deprez P, Royer J, Husson HP. Tetrahedron: Asymmetry 1991; 2: 1189
  • 20 Crude NMR spectral data of 18a are supplied in the Supporting Information.
  • 21 Crude NMR spectra of 18b did not give information about the diastereomeric ratio, but the hydrolyzed product 18b′ (Figure 1, see Supporting Information) allowed this problem to be solved.

    • l-N-Methylserine was prepared and characterized: mp 190 °C (dec.); [α]D 21 +30.5 (c 1.0, 6 N HCl).
    • 22a F. Hoffmann-La Roche & Co. A.-G. Patent BE 616021, 1963 ; Chem. Abstr. 1963, 58, 66783.
    • 22b Aurelio L, Brownlee RT. C, Hughes AB, Sleebs BE. Aust. J. Chem. 2000; 53: 425
  • 23 Lubineau A, Bouchain G, Queneau Y. J. Chem. Soc., Perkin Trans. 1 1995; 2433
  • 24 Bureau R, Mortier J, Joucla M. Bull. Soc. Chim. Fr. 1993; 130: 584