Synthesis 2016; 48(06): 906-916
DOI: 10.1055/s-0035-1560404
paper
© Georg Thieme Verlag Stuttgart · New York

A Short Access to Symmetrically α,α-Disubstituted α-Amino Acids from Acyl Cyanohydrins

Fatma Boukattaya
a  LUNAM Université, Université du Maine, CNRS UMR 6283, Institut des Molécules et Matériaux du Mans (IMMM), 72085 Le Mans Cedex 09, France   Email: philippe.bertus@univ-lemans.fr
b  Laboratory of Applied Chemistry HCGP, Faculty of Science, University of Sfax, 3000 Sfax, Tunisia
,
Julien Caillé
a  LUNAM Université, Université du Maine, CNRS UMR 6283, Institut des Molécules et Matériaux du Mans (IMMM), 72085 Le Mans Cedex 09, France   Email: philippe.bertus@univ-lemans.fr
,
Houcine Ammar
b  Laboratory of Applied Chemistry HCGP, Faculty of Science, University of Sfax, 3000 Sfax, Tunisia
,
Florian Rouzier
a  LUNAM Université, Université du Maine, CNRS UMR 6283, Institut des Molécules et Matériaux du Mans (IMMM), 72085 Le Mans Cedex 09, France   Email: philippe.bertus@univ-lemans.fr
,
Fabien Boeda
a  LUNAM Université, Université du Maine, CNRS UMR 6283, Institut des Molécules et Matériaux du Mans (IMMM), 72085 Le Mans Cedex 09, France   Email: philippe.bertus@univ-lemans.fr
,
Morwenna S. M. Pearson-Long
a  LUNAM Université, Université du Maine, CNRS UMR 6283, Institut des Molécules et Matériaux du Mans (IMMM), 72085 Le Mans Cedex 09, France   Email: philippe.bertus@univ-lemans.fr
,
Philippe Bertus*
a  LUNAM Université, Université du Maine, CNRS UMR 6283, Institut des Molécules et Matériaux du Mans (IMMM), 72085 Le Mans Cedex 09, France   Email: philippe.bertus@univ-lemans.fr
› Author Affiliations
Further Information

Publication History

Received: 23 October 2015

Accepted after revision: 02 December 2015

Publication Date:
13 January 2016 (online)

Abstract

A straightforward synthesis of symmetrically α,α-disubstituted α-amino acids is presented. The key step of this process relies on the efficient double addition of Grignard reagents to acyl cyanohydrins to provide N-acyl amino alcohols selectively in good yields. The chemoselectivity of the reaction was modulated by the nature of the acyl moiety. Eleven amino acids were prepared, including the particularly simple divinylglycine, which is not easily accessible by using conventional methods.

Supporting Information

 
  • References

    • 1a Kotha S, Goyal D, Chavan AS. J. Org. Chem. 2013; 78: 12288
    • 1b Soloshonok VA, Sorochinsky AE. Synthesis 2010; 2319
    • 1c Cativiela C, Díaz-de-Villegas MD. Tetrahedron: Asymmetry 2007; 18: 569
    • 1d Vogt H, Bräse S. Org. Biomol. Chem. 2007; 5: 406
    • 1e Ohfune Y, Shinada T. Eur. J. Org. Chem. 2005; 5127
    • 1f Wirth T. Angew. Chem., Int. Ed. Engl. 1997; 36: 225
    • 2a Venkatraman J, Shankaramma SC, Balaram P. Chem. Rev. 2001; 101: 3131
    • 2b Tanaka M. Chem. Pharm. Bull. 2007; 55: 349
    • 2c Crisma M, Saviano M, Moretto A, Broxterman QB, Kaptein B, Toniolo C. J. Am. Chem. Soc. 2007; 129: 15471
  • 3 Stähelin H, Trippmacher A. Eur. J. Cancer 1974; 10: 801
    • 4a Toniolo C, Brückner H. Peptaibiotics . Wiley-VCH; Weinheim: 2009

    • Special issues on peptaibiotics:
    • 4b Chem. Biodivers. 2007; 4: 1021
    • 4c Chem. Biodivers. 2013; 10: 731

      See, for example:
    • 5a Castro TG, Micaêlo NM. J. Phys. Chem. B 2014; 118: 649
    • 5b Žukauskaitė A, Moretto A, Peggion C, De Zotti M, Sačkus A, Formaggio F, De Kimpe N, Mangelinckx S. Eur. J. Org. Chem. 2014; 2312
    • 5c Guitot K, Larregola M, Pradan TK, Vasse J.-L, Lavielle S, Bertus P, Szymoniak J, Lequin O, Karoyan P. ChemBioChem 2011; 12: 1039
    • 5d Lígia M, Rodrigues LM, Fonseca JI, Maia HL. S. Tetrahedron 2004; 60: 8929
  • 6 Yamagushi H, Kodama H, Osada S, Kato F, Jelokhani-Niaraki M, Kondo M. Biosci., Biotechnol., Biochem. 2003; 67: 2269
  • 7 Ware E. Chem. Rev. 1950; 46: 403
  • 8 Wang B, Zhang W, Zhang L, Du D.-M, Liu G, Xu J. Eur. J. Org. Chem. 2008; 350
  • 9 Pinto FC. S. C, Pereira-Lima SM. M. A, Maia HL. S. Tetrahedron 2009; 65: 9165
    • 10a Mosey RA, Fisk JS, Tepe JJ. Tetrahedron: Asymmetry 2008; 19: 2755
    • 10b Casabona D, Cativiela C. Synthesis 2006; 2440
    • 11a Hatano M, Yamashita K, Mizuno M, Ito O, Ishihara K. Angew. Chem. Int. Ed. 2015; 54: 2707
    • 11b Finkbeiner P, Weckenmann NM, Nachtshein B. Org. Lett. 2014; 16: 1326
    • 11c Li K, Tan G, Huang J, Song F, You J. Angew. Chem. Int. Ed. 2013; 52: 12942
    • 11d Hata S, Koyama H, Shimizu M. J. Org. Chem. 2011; 76: 9670 ; and references therein
  • 12 Hilinski GJ, Kim Y.-W, Hong J, Kutchukian PS, Crenshaw CM, Berkovitch SS, Chang A, Ham S, Verdine G. J. Am. Chem. Soc. 2014; 136: 12314

    • See, for instance, Huisgen reaction:
    • 13a Testa T, Scrima M, Grimaldi M, D’Ursi AM, Dirain ML, Lubin-Germain N, Singh A, Haskell-Luevano C, Chorev M, Rovero P, Papini AM. J. Med. Chem. 2014; 57: 9424
    • 13b Cantel S, Le Chevalier Isaad A, Scrima M, Levy JJ, DiMarchi RD, Rovero P, Halperin JA, D’Ursi AM, Papini AM, Chorev M. J. Org. Chem. 2008; 73: 5663
    • 13c Thiol-ene reaction: Karman L, Kazmaier U. Eur. J. Org. Chem. 2013; 7101
    • 14a Bertus P, Szymoniak J. Chem. Commun. 2001; 1792
    • 14b Bertus P, Szymoniak J. J. Org. Chem. 2003; 68: 7133
    • 14c Laroche C, Bertus P, Szymoniak J. Chem. Commun. 2005; 3030
    • 14d Laroche C, Harakat D, Bertus P, Szymoniak J. Org. Biomol. Chem. 2005; 3: 3482
    • 14e Bertus P, Szymoniak J. Org. Lett. 2007; 9: 659
    • 14f Pearson MS. M, Floquet N, Bello C, Vogel P, Plantier-Royon R, Szymoniak J, Bertus P, Behr J.-B. Bioorg. Med. Chem. 2009; 17: 8020
    • 16a Bertus P, Szymoniak J. J. Org. Chem. 2002; 67: 3965
    • 16b Joosten A, Vasse JL, Bertus P, Szymoniak J. Synlett 2008; 2455
    • 16c Pradhan TK, Joosten A, Vasse JL, Bertus P, Karoyan P, Szymoniak J. Eur. J. Org. Chem. 2009; 5072
    • 16d Pearson-Long MS. M, Beauseigneur A, Karoyan P, Szymoniak J, Bertus P. Synthesis 2010; 3410
    • 17a Setzer P, Beauseigneur A, Pearson-Long MS. M, Bertus P. Angew. Chem. Int. Ed. 2010; 49: 8691
    • 17b Setzer P, Forcher G, Boeda F, Pearson-Long MS. M, Bertus P. Eur. J. Org. Chem. 2014; 171
  • 18 Boukattaya F, Stanovych A, Setzer P, Abid S, Ammar H, Pearson-Long MS. M, Bertus P. Chem. Commun. 2012; 48: 8655
  • 19 The numbering of molecules 2 and 5 are as follows: the first letter refers to the acyl group (a: R1 = Ph), and the second letter to the R2 group introduced by the Grignard reagent (a: R2 = Et).
    • 20a Erker G, Riedel M, Koch S, Jodicke T, Wiirthwein E.-U. J. Org. Chem. 1995; 60: 5284
    • 20b Bouchoule C, Miginiac P. C. R. Seances Acad. Sci., Ser. C 1968; 266: 1614
    • 21a Beumer R, Bubert C, Cabrele C, Vielhauer O, Pietzsch M, Reiser O. J. Org. Chem. 2000; 65: 8960
    • 21b Dalcanale E, Montanari F. J. Org. Chem. 1986; 50: 567

      For the synthesis of divinylglycine derivatives:
    • 22a Opio JO, Labidalle S, Galons H, Miocques M, Zaparucha A, Loupy A. Synth. Commun. 1991; 21: 1743
    • 22b Simila ST. M, Martin SF. Tetrahedron Lett. 2008; 49: 4501
  • 23 Love BE, Jones EG. J. Org. Chem. 1999; 64: 3755
  • 24 Shen R, Lin CT, Bowman EJ, Bowman BJ, Porco JA. Jr. J. Am. Chem. Soc. 2003; 125: 7889
  • 25 Shiau TP, Houchin A, Nair S, Xu P, Low E, Najafi R, Jain R. Bioorg. Med. Chem. Lett. 2009; 19: 1110
  • 26 Hunt T, Atherton-Watson HC, Collingwood SP, Coote KJ, Czarnecki S, Danahay H, Howsham C, Hunt P, Paisley D, Young A. Bioorg. Med. Chem. Lett. 2012; 22: 2877
  • 27 Balamurugan D, Muraleedharan KM. Chem. Eur. J. 2012; 18: 9516
  • 28 Zanardi F, Battistini L, Rassu G, Cornia M, Casiraghi G. J. Chem. Soc., Perkin Trans. 1 1995; 2471
  • 29 Dumbris SM, Diaz DJ, McElwee-White L. J. Org. Chem. 2009; 74: 8862
  • 30 Kotha S, Sreenivasachary N, Mohanraja K, Durani S. Bioorg. Med. Chem. Lett. 2001; 11: 1421
    • 31a Ropenga J, Grudzinski S. Acta Pol. Pharm. 1984; 41: 579
    • 31b Guryn R, Kotelko A, Majchrzak M. Acta Pol. Pharm. 1975; 32: 533