Advertisement

Amino Acids

pp 1–12 | Cite as

The self-disproportionation of enantiomers (SDE) of α-amino acid derivatives: facets of steric and electronic properties

  • Takuma Hosaka
  • Tomomi Imai
  • Alicja Wzorek
  • Magdalena Marcinkowska
  • Anna Kolbus
  • Osamu Kitagawa
  • Vadim A. Soloshonok
  • Karel D. Klika
Original Article

Abstract

α-Amino acids (α-AAs) are in extremely high demand in nearly every sector of the food and health-related chemical industries and continue to be the subject of intense multidisciplinary research. The self-disproportionation of enantiomers (SDE) is an emerging and one of the least studied areas of α-AA or enantiomeric properties, critically important for their production and application. In the present work, we report a detailed study of the SDE via achiral, gravity-driven column chromatography for a set of N-acylated, N-carbonylated, N-fluoroacylated, and N-thioacylated α-amino acid esters. As well as thioacylation, attention was paid to the effect of altering the R group of the ester functionality, the side chain, or that of the acyl group attached to the amide nitrogen, whereby it was found that electron-withdrawing groups in the latter moiety had a pronounced effect on the magnitude and behavior of the resulting SDE phenomenon. Intriguingly, in the case of N-fluoroacylated derivatives, by favoring the formation of dimeric associates and effecting a strong bias toward homochiral associates over heterochiral associates, the SDE magnitude was greatly reduced contrary to intuitive expectations. Energy estimates resulted from DFT calculations.

Keywords

Molecular chirality Self-disproportionation of enantiomers (SDE) N-(Thio)acylated α-amino acid esters Achiral column chromatography Enantioenrichment/-depletion DFT calculations 

Notes

Acknowledgements

The authors gratefully acknowledge financial support from the Ministry of Science and Higher Education, Poland (Grant no. 612 512, AW) and IKERBASQUE, the Basque Foundation for Science, Spain (VAS).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing financial interests.

Supplementary material

726_2018_2664_MOESM1_ESM.docx (3 mb)
Supplementary material 1 (DOCX 3093 kb)

References

  1. Abás S, Arróniz C, Molins E, Escolano C (2018) Access to the enantiopure pyrrolobenzodiazepine (PBD) dilactam nucleus via self-disproportionation of enantiomers. Tetrahedron 74:867–871CrossRefGoogle Scholar
  2. Aceña JL, Sorochinsky AE, Moriwaki H, Sato T, Soloshonok VA (2013a) Synthesis of fluorine-containing α-amino acids in enantiomerically pure form via homologation of Ni(II) complexes of glycine and alanine Schiff bases. J Fluor Chem 155:21–38CrossRefGoogle Scholar
  3. Aceña JL, Sorochinsky AE, Katagiri T, Soloshonok VA (2013b) Unconventional preparation of racemic crystals of isopropyl 3,3,3-trifluoro-2-hydroxypropanoate and their unusual crystallographic structure: the ultimate preference for homochiral intermolecular interactions. Chem Commun 49:373–375CrossRefGoogle Scholar
  4. Aceña JL, Sorochinsky AE, Soloshonok VA (2014) Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 3: michael addition reactions and miscellaneous transformations. Amino Acids 46:2047–2073CrossRefGoogle Scholar
  5. Baciocchi R, Zenoni G, Mazzotti M, Morbidelli M (2002) Separation of binaphthol enantiomers through achiral chromatography. J Chromatogr A 944:225–240CrossRefGoogle Scholar
  6. Baciocchi R, Mazzotti M, Morbidelli M (2004) General model for the achiral chromatography of enantiomers forming dimers: application to binaphthol. J Chromatogr A 1024:15–20CrossRefGoogle Scholar
  7. Bravo P, Farina A, Frigerio M, Valdo Meille S, Viani F, Soloshonok VA (1994) New fluorinated chiral synthons. Tetrahedron Asymmetry 5:987–1004CrossRefGoogle Scholar
  8. Bravo P, Farina A, Kukhar VP, Markovsky AL, Meille SV, Soloshonok VA, Sorochinsky AE, Viani F, Zanda M, Zappala C (1997) Stereoselective additions of α-lithiated alkyl-p-tolylsulfoxides to N-PMP(fluoroalkyl)aldimines. An efficient approach to enantiomerically pure fluoro amino compounds. J Org Chem 62:3424–3425CrossRefGoogle Scholar
  9. Bravo P, Guidetti M, Viani F, Zanda M, Markovsky AL, Sorochinsky AE, Soloshonok IV, Soloshonok VA (1998) Chiral sulfoxide controlled asymmetric additions to C–N double bond. An efficient approach to stereochemically defined α-fluoroalkyl amino compounds. Tetrahedron 54:12789–12806CrossRefGoogle Scholar
  10. Drabowicz J, Jasiak A, Wzorek A, Sato A, Soloshonok VA (2017) Self-disproportionation of enantiomers (SDE) of chiral sulfoxides, amides and thioamides via achiral chromatography. Arkivoc 2017:557–578CrossRefGoogle Scholar
  11. Ellis TK, Ueki H, Yamada T, Ohfune Y, Soloshonok VA (2006) Design, synthesis, and evaluation of a new generation of modular nucleophilic glycine equivalents for the efficient synthesis of sterically constrained α-amino acids. J Org Chem 71:8572–8578CrossRefGoogle Scholar
  12. Gibson SE, Guillo N, Tozer MJ (1999) Towards control of χ-space: conformationally constrained analogues of Phe, Tyr, Trp and His. Tetrahedron 55:585–615CrossRefGoogle Scholar
  13. Gil-Av E, Schurig V (1994) Resolution of non-racemic mixtures in achiral chromatographic systems: a model for the enantioselective effects observed. J Chromatogr A 666:519–525CrossRefGoogle Scholar
  14. Han J, Nelson DJ, Sorochinsky AE, Soloshonok VA (2011) Self-disproportionation of enantiomers via sublimation; new and truly green dimension in optical purification. Curr Org Synth 8:310–317CrossRefGoogle Scholar
  15. Han J, Soloshonok VA, Klika KD, Drabowicz J, Wzorek A (2018a) Chiral sulfoxides: advances in asymmetric synthesis and problems with the accurate determination of the stereochemical outcome. Chem Soc Rev 47:1307–1350CrossRefGoogle Scholar
  16. Han J, Kitagawa O, Wzorek A, Klika KD, Soloshonok VA (2018b) The self-disproportionation of enantiomers (SDE): a menace or an opportunity? Chem Sci 9:1718–1739CrossRefGoogle Scholar
  17. He G, Wang B, Nack WA, Chen G (2016) Syntheses and transformations of α-amino acids via palladium-catalyzed auxiliary-directed sp3 C-H functionalization. Acc Chem Res 49:635–645CrossRefGoogle Scholar
  18. Hodgson DRW, Sanderson JM (2004) The synthesis of peptides and proteins containing non-natural amino acids. Chem Soc Rev 33:422–430CrossRefGoogle Scholar
  19. Jung M, Schurig V (1992) Computer simulation of three scenarios for the separation of non-racemic mixtures by chromatography on achiral stationary phases. J Chromatogr 605:161–166CrossRefGoogle Scholar
  20. Klika KD, Budovská M, Kutschy P (2010) NMR spectral enantioresolution of spirobrassinin and 1-methoxyspirobrassinin enantiomers using (S)-(-)-ethyl lactate and modeling of spirobrassinin self-association for rationalization of its self-induced diastereomeric anisochronism (SIDA) and enantiomer self-disproportionation on achiral-phase chromatography (ESDAC) phenomena. J Fluor Chem 131:467–476CrossRefGoogle Scholar
  21. Kukhar VP, Sorochinsky AE, Soloshonok VA (2009) Practical synthesis of fluorine-containing α- and β-amino acids: recipes from Kiev, Ukrain. Future Med Chem 1:793–819CrossRefGoogle Scholar
  22. Ma JS (2003) Unnatural amino acids in drug discovery. Chim Oggi/Chem Today 21:65–68Google Scholar
  23. Maeno M, Tokunaga E, Yamamoto T, Suzuki T, Ogino Y, Ito E, Shiro M, Asahi T, Shibata N (2015) Self-disproportionation of enantiomers of thalidomide and its fluorinated analogue via gravity-driven achiral chromatography: mechanistic rationale and implications. Chem Sci 6:1043–1048CrossRefGoogle Scholar
  24. Martens J, Bhushan R (1992) Resolution of enantiomers with achiral phase chromatography. J Liq Chromatogr Relat Technol 15:1–27CrossRefGoogle Scholar
  25. Martens J, Bhushan R (2014) Purification of enantiomeric mixtures in enantioselective synthesis: overlooked errors and scientific basis of separation in achiral environment. Helv Chim Acta 97:161–187CrossRefGoogle Scholar
  26. Martens J, Bhushan R (2016) Enantioseparations in achiral environments and chromatographic systems. Isr J Chem 56:990–1009CrossRefGoogle Scholar
  27. Mayani VJ, Abdi SHR, Kureshy RI, Khan NH, Agrawal S, Jasra RV (2009) Enantiomer self-disproportionation of chiral compounds on achiral ordered mesoporous silica M41S and regular silica gel as a stationary phase. Chirality 21:255–261CrossRefGoogle Scholar
  28. Metz AE, Kozlowski MC (2015) Recent advances in asymmetric catalytic methods for the formation of acyclic α,α-disubstituted α-amino acids. J Org Chem 80:1–7CrossRefGoogle Scholar
  29. Mikami K, Fustero S, Sánchez-Roselló M, Aceña JL, Soloshonok VA, Sorochinsky AE (2011) Synthesis of fluorinated β-amino acids. Synthesis 2011:3045–3079CrossRefGoogle Scholar
  30. Mikhailiuk PK, Afonin S, Chernega AN, Rusanov EB, Platonov MO, Dubinina GG, Berditsch M, Ulrich AS, Komarov IV (2006) Conformationally rigid trifluoromethyl-substituted α-amino acid designed for peptide structure analysis by solid-state 19F NMR spectroscopy. Angew Chem Int Ed 45:5659–5661CrossRefGoogle Scholar
  31. Monde K, Harada N, Takasugi M, Kutschy P, Suchý M, Dzurilla M (2000) Enantiomeric excess of a cruciferous phytoalexin, spirobrassinin, and its enantiomeric enrichment in an achiral HPLC system. J Nat Prod 63:1312–1314CrossRefGoogle Scholar
  32. Nakamura T, Tateishi K, Tsukagoshi S, Hashimoto S, Watanabe S, Soloshonok VA, Aceña JL, Kitagawa O (2012) Self-disproportionation of enantiomers of non-racemic chiral amine derivatives through achiral chromatography. Tetrahedron 68:4013–4017CrossRefGoogle Scholar
  33. Ogawa S, Nishimine T, Tokunaga E, Nakamura S, Shibata N (2010) Self-disproportionation of enantiomers of heterocyclic compounds having a tertiary trifluoromethyl alcohol center on chromatography with a non-chiral system. J Fluor Chem 131:521–524CrossRefGoogle Scholar
  34. Reyes-Rangel G, Vargas-Caporali J, Juaristi E (2017) Asymmetric Michael addition reaction organocatalyzed by stereoisomeric pyrrolidine sulfinamides under neat conditions. A brief study of self-disproportionation of enantiomers. Tetrahedron 73:4707–4718CrossRefGoogle Scholar
  35. Sato T, Izawa K, Aceña JL, Liu H, Soloshonok VA (2016) Tailor-made α-amino acids in the pharmaceutical industry: synthetic approaches to (1R,2S)-1-amino-2-vinylcyclopropane-1-carboxylic acid (vinyl-ACCA). Eur J Org Chem 2016:2757–2774CrossRefGoogle Scholar
  36. Schurig V (2009) Elaborate treatment of retention in chemoselective chromatography—the retention increment approach and nonlinear effects. J Chromatogr A 1216:1723–1736CrossRefGoogle Scholar
  37. So SM, Kim H, Mui L, Chin J (2012) Mimicking nature to make unnatural amino acids and chiral diamines. Eur J Org Chem 2012:229–241CrossRefGoogle Scholar
  38. Soloshonok VA (2002) Highly diastereoselective Michael addition reactions between nucleophilic glycine equivalents and β-substituted-α,β-unsaturated carboxylic acid derivatives a general approach to the stereochemically defined and sterically χ-constrained & α-amino acids. Curr Org Chem 6:341–364CrossRefGoogle Scholar
  39. Soloshonok VA (2006) Remarkable amplification of the self-disproportionation of enantiomers on achiral-phase chromatography columns. Angew Chem Int Ed 45:766–769CrossRefGoogle Scholar
  40. Soloshonok VA, Berbasov DO (2006a) Self-disproportionation of enantiomers on achiral phase chromatography. One more example of fluorine’s magic powers. Chim Oggi Chem Today 24:44–47Google Scholar
  41. Soloshonok VA, Berbasov DO (2006b) Self-disproportionation of enantiomers of (R)-ethyl 3-(3,5-dinitrobenzamido)-4,4,4-trifluorobutanoate on achiral silica gel stationary phase. J Fluor Chem 127:597–603CrossRefGoogle Scholar
  42. Soloshonok VA, Ono T (1996) The effect of substituents on the feasibility of azomethine–azomethine isomerization: new synthetic opportunities for biomimetic transamination. Tetrahedron 52:14701–14712CrossRefGoogle Scholar
  43. Soloshonok VA, Sorochinsky AE (2010) Practical methods for the synthesis of symmetrically αα-disubstituted α-amino acids. Synthesis 2010:2319–2344CrossRefGoogle Scholar
  44. Soloshonok VA, Kirilenko AG, Kukhar VP, Resnati G (1993a) Transamination of fluorinated β-keto carboxylic esters. A biomimetic approach to β-polyfluoroalkyl-β-amino acids. Tetrahedron Lett 34:3621–3624CrossRefGoogle Scholar
  45. Soloshonok VA, Kukhar VP, Galushko SV, Svistunova NY, Avilov DV, Kuzmina NA, Raevski NI, Struchkov YT, Pisarevsky AP, Belokon YN (1993b) General method for the synthesis of enantiomerically pure β-hydroxy-α-amino acids, containing fluorine atoms in the side chains. Case of stereochemical distinction between methyl and trifluoromethyl groups. X-Ray crystal and molecular structure of the nickel(II) complex of (2S,3S)-2(trifluoromethyl)threonine. J Chem Soc Perkin Trans 1:3143–3155CrossRefGoogle Scholar
  46. Soloshonok VA, Avilov DV, Kukhar VP (1996a) Asymmetric aldol reactions of trifluoromethyl ketones with a chiral Ni(II) complex of glycine: stereocontrolling effect of the trifluoromethyl group. Tetrahedron 52:12433–12442CrossRefGoogle Scholar
  47. Soloshonok VA, Avilov DV, Kukhar VP (1996b) Highly diastereoselective asymmetric aldol reactions of chiral Ni(II)-complex of glycine with alkyl trifluoromethyl ketones. Tetrahedron Asymmetry 7:1547–1550CrossRefGoogle Scholar
  48. Soloshonok VA, Cai C, Hruby VJ, Meervelt LV, Mischenko N (1999) Stereochemically defined C-substituted glutamic acids and their derivatives. 1. An efficient asymmetric synthesis of (2S,3S)-3-methyl- and -3-trifluoromethylpyroglutamic acids. Tetrahedron 55:12031–12044CrossRefGoogle Scholar
  49. Soloshonok VA, Ueki H, Ellis TK, Yamada T, Ofhune Y (2005) Application of modular nucleophilic glycine equivalents for truly practical asymmetric synthesis of β-substituted pyroglutamic acids. Tetrahedron Lett 46:1107–1110CrossRefGoogle Scholar
  50. Soloshonok VA, Roussel Ch, Kitagawa O, Sorochinsky AE (2012) Self-disproportionation of enantiomers via achiral chromatography: a warning and an extra dimension in optical purifications. Chem Soc Rev 41:4180–4188CrossRefGoogle Scholar
  51. Soloshonok VA, Wzorek A, Klika KD (2017) A question of policy: should tests for the self-disproportionation of enantiomers (SDE) be mandatory for reports involving scalemates? Tetrahedron Asymmetry 28:1430–1434CrossRefGoogle Scholar
  52. Sorochinsky AE, Soloshonok VA (2013) In Self-disproportionation of enantiomers of enantiomerically enriched compounds in topics in current chemistry. In: Schurig V (ed) Differentiation of enantiomers II, vol 341. Springer-Verlag GmbH, Berlin, pp 301–340CrossRefGoogle Scholar
  53. Sorochinsky AE, Aceña JL, Moriwaki H, Sato T, Soloshonok VA (2013a) Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases; Part 1: alkyl halide alkylations. Amino Acids 45:691–718CrossRefGoogle Scholar
  54. Sorochinsky AE, Aceña JL, Moriwaki H, Sato T, Soloshonok VA (2013b) Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 2: aldol, Mannich addition reactions, deracemization and (S) to (R) interconversion of α-amino acids. Amino Acids 45:1017–1033CrossRefGoogle Scholar
  55. Sorochinsky AE, Aceña JL, Soloshonok VA (2013c) Self-disproportionation of enantiomers of chiral, non-racemic fluoroorganic compounds: role of fluorine as enabling element. Synthesis 45:141–152Google Scholar
  56. Sorochinsky AE, Katagiri T, Ono T, Wzorek A, Aceña JL, Soloshonok VA (2013d) Optical purifications via self-disproportionation of enantiomers by achiral chromatography: case study of a series of α-CF3-containing secondary alcohols. Chirality 25:365–368CrossRefGoogle Scholar
  57. Suchý M, Kutschy P, Monde K, Goto H, Harada N, Takasugi M, Dzurilla M, Balentová E (2001) Synthesis, absolute configuration, and enantiomeric enrichment of a cruciferous oxindole phytoalexin, (S)-(−)-spirobrassinin, and its oxazoline analog. J Org Chem 66:3940–3947CrossRefGoogle Scholar
  58. Suzuki Y, Han J, Kitagawa O, Aceña JL, Klika KD, Soloshonok VA (2015) A comprehensive examination of the self-disproportionation of enantiomers (SDE) of chiral amides via achiral, laboratory-routine, gravity-driven column chromatography. RSC Adv 5:2988–2993CrossRefGoogle Scholar
  59. Ueki H, Yasumoto M, Soloshonok VA (2010) Rational application of self-disproportionation of enantiomers via sublimation—a novel methodological dimension for enantiomeric purifications. Tetrahedron Asymmetry 21:1396–1400CrossRefGoogle Scholar
  60. Urman S, Gaus K, Yang Y, Strijowski U, Sewald N, De Pol S, Reiser O (2007) The constrained amino acid & β-Acc confers potency and selectivity to integrin ligands. Angew Chem Int Ed 46:3976–3978CrossRefGoogle Scholar
  61. Wzorek A, Klika KD, Drabowicz J, Sato A, Aceña JL, Soloshonok VA (2014) The self-disproportionation of the enantiomers (SDE) of methyl n-pentyl sulfoxide via achiral, gravity-driven column chromatography: a case study. Org Biomol Chem 12:4738–4746CrossRefGoogle Scholar
  62. Wzorek A, Sato A, Drabowicz J, Soloshonok VA, Klika KD (2015) Enantiomeric enrichments via the self-disproportionation of enantiomers (SDE) by achiral, gravity-driven column chromatography: a case study using N-(1-phenylethyl)acetamide for optimizing the enantiomerically pure yield and magnitude of the SDE. Helv Chem Acta 98:1147–1159CrossRefGoogle Scholar
  63. Wzorek A, Sato A, Drabowicz J, Soloshonok VA (2016a) Self-disproportionation of enantiomers via achiral gravity-driven column chromatography: a case study of N-acyl-α-phenylethylamines. J Chromatogr A 1467:270–278CrossRefGoogle Scholar
  64. Wzorek A, Sato A, Drabowicz J, Soloshonok VA (2016b) Self-disproportionation of enantiomers (SDE) of chiral nonracemic amides via achiral chromatography. Isr J Chem 56:977–989CrossRefGoogle Scholar
  65. Wzorek A, Sato A, Drabowicz J, Soloshonok VA, Klika KD (2016c) Remarkable magnitude of the self-disproportionation of enantiomers (SDE) via achiral chromatography: application to the practical-scale enantiopurification of β-amino acid esters. Amino Acids 48:605–613CrossRefGoogle Scholar
  66. Wzorek A, Kamizela A, Sato A, Soloshonok VA (2017) Self-disproportionation of enantiomers (SDE) via achiral gravity-driven column chromatography of N-fluoroacyl-1-phenylethylamines. J Fluor Chem 196:37–43CrossRefGoogle Scholar
  67. Yasumoto M, Ueki H, Soloshonok VA (2010) Self-disproportionation of enantiomers of 3,3,3-trifluorolactic acid amides via sublimation. J Fluor Chem 131:266–269CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Applied ChemistryShibaura Institute of TechnologyTokyoJapan
  2. 2.Institute of ChemistryJan Kochanowski University in KielceKielcePoland
  3. 3.Department of Organic Chemistry I, Faculty of ChemistryUniversity of the Basque Country UPV/EHUSan SebastiánSpain
  4. 4.IKERBASQUE, Basque Foundation for ScienceBilbaoSpain
  5. 5.Molecular Structure Analysis, German Cancer Research Center (DKFZ)HeidelbergGermany

Personalised recommendations