Enantiodifferentiation of phytoalexin spirobrassinin derivatives using the chiral solvating agent (R)-(+)-1,1′-bi-2-naphthol in conjunction with molecular modeling

Abstract The enantioresolutions of chiral phytoalexins spirobrassinin, 1-methoxyspirobrassinin and cis - and trans -1-methoxyspirobrassinol methyl ethers were obtained by solution-state 1 H NMR spectroscopy using the chiral solvating agents ( R )-(+)-1,1′-bi-2-naphthol and, for 1-methoxyspirobrassinin, ( R )-(−)-1-phenyl-2,2,2-trifluoroethanol. In addition to the evaluation of the magnitude of the chemical shift differences, several other aspects with respect to enantiodifferentiation were also examined, namely titration of the enantiomers with the chiral solvating agents, signal degradation in the presence of excess, solid binaphthol, measurement of longitudinal relaxation times ( T 1 ) and diffusion coefficients ( D ), conducting enantiomeric titrations of spirobrassinin under SIDA and atypical SIDA conditions, and conducting chromatographic-type examinations (‘TLC in an NMR tube’). To rationalize the observed spectroscopic and adsorption behavior, the conformations, geometries, and energies of the complexes were calculated by DFT calculations at the B3LYP/TZVP{6-31G(d,p)} level of theory with solvation simulated by IEF-PCM. Chemical shifts were assessed by making a comparison with population-weighted averaged shieldings calculated by DFT at the B3LYP/cc-pVTZ level of theory using the GIAO method. The reliability of the interpretations with respect to the assignment of the configuration was very dependent on obtaining a large calculated Δ G and/or adopting a holistic approach by evaluating several measured parameters.

[1]  M. Shapiro,et al.  NUCLEAR OVERHAUSER EFFECT ON DIFFUSION MEASUREMENTS , 1999 .

[2]  K. Pihlaja,et al.  Stereochemistry, tautomerism, and reactions of acridinyl thiosemicarbazides in the synthesis of 1,3-thiazolidines † , 2006 .

[3]  K. Pihlaja,et al.  Modeling NMR parameters by DFT methods as an aid to the conformational analysis of cis-fused 7a(8a)-methyl octa(hexa)hydrocyclopenta[d][1,3]oxazines and [3,1]benzoxazines. , 2003, Journal of the American Chemical Society.

[4]  E. Domenici,et al.  Conformational and dynamic changes of D- and L-tryptophan due to stereoselective interaction with human serum albumin, as revealed by proton-selective relaxation rate measurements , 1991 .

[5]  K. Müller.  Studies on Phytoalexins I. The Formation and the Immunological Significance of Phytoalexin Produced by Phaseolus Vulgaris in Response to Infections With Sclerotinia Fructicola and Phytophthora Infestans , 1958 .

[6]  K. Monde,et al.  Stereoselective synthesis of (R)-(+)-1-methoxyspirobrassinin, (2R,3R)-( )-1-methoxyspirobrassinol methyl ether and their enantiomers or diastereoisomers , 2007 .

[7]  Michael J. Shapiro,et al.  Chemical Exchange in Diffusion NMR Experiments , 1998 .

[8]  Leo Radom,et al.  Harmonic Vibrational Frequencies: An Evaluation of Hartree−Fock, Møller−Plesset, Quadratic Configuration Interaction, Density Functional Theory, and Semiempirical Scale Factors , 1996 .

[9]  Ville Nieminen,et al.  NMR and molecular modeling of the dimeric self-association of the enantiomers of 1,1'-bi-2-naphthol and 1-phenyl-2,2,2-trifluoroethanol in the solution state and their relevance to enantiomer self-disproportionation on achiral-phase chromatography (ESDAC). , 2009, Organic & biomolecular chemistry.

[10]  K. Klika.  Use of sub-stoichiometric amounts of chiral auxiliaries for enantiodifferentiation by NMR; caveats and potential utility , 2009 .

[11]  T. Wenzel,et al.  Chiral reagents for the determination of enantiomeric excess and absolute configuration using NMR spectroscopy. , 2003, Chirality.

[12]  L. Kronberg,et al.  Restricted rotation/tautomeric equilibrium and determination of the site and extent of protonation in bi-imidazole nucleosides by multinuclear NMR and GIAO-DFT calculations , 2005 .

[13]  D. Hoover,et al.  NMR Chiral Solvating Agents , 2007 .

[14]  Nobuaki Miura,et al.  Chiral cruciferous phytoalexins: preparation, absolute configuration, and biological activity. , 2005, Bioorganic & medicinal chemistry.

[15]  Molecular diffusion in liquid crystals and chiral discrimination. II. Model calculations. , 2006, The Journal of chemical physics.

[16]  D. Parker.  NMR Determination of Enantiomeric Purity , 1991 .

[17]  R. Carman,et al.  The Optical Fractionation of a Partially Racemic Natural Product by Chromatography Over an Achiral Substrate , 1991 .

[18]  A. Becke,et al.  Density-functional exchange-energy approximation with correct asymptotic behavior. , 1988, Physical review. A, General physics.

[19]  Charles S. Johnson,et al.  An Improved Diffusion-Ordered Spectroscopy Experiment Incorporating Bipolar-Gradient Pulses , 1995 .

[20]  K. Klika,et al.  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 anisochromism (SIDA) and enantiomer self-disproportionation on achiral-phase chr , 2010 .

[21]  K. Monde,et al.  Three sulphur-containing stress metabolites from Japanese radish☆ , 1995 .

[22]  A. Becke.  Density-functional thermochemistry. III. The role of exact exchange , 1993 .

[23]  G. Uccello-Barretta,et al.  NMR Enantiodiscrimination Phenomena by Quinine C9-Carbamates , 2009 .

[24]  S. Böhm,et al.  Spectroscopic, structural and theoretical studies of novel, potentially cytotoxic 4-acridonecarboxamide imines. , 2009, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[25]  M. Pedras,et al.  Phytoalexins from crucifers: synthesis, biosynthesis, and biotransformation. , 2000, Phytochemistry.

[26]  N. Harada,et al.  Synthesis, absolute configuration, and enantiomeric enrichment of a cruciferous oxindole phytoalexin, (S)-(-)-spirobrassinin, and its oxazoline analog. , 2001, The Journal of organic chemistry.

[27]  G. Moro,et al.  Molecular diffusion in liquid crystals and chiral discrimination. I. Theory. , 2005, The Journal of chemical physics.

[28]  M. Suchý,et al.  Cruciferous phytoalexins: antiproliferative effects in T-Jurkat leukemic cells. , 2005, Leukemia research.

[29]  N. Harada,et al.  Spirocyclization strategy toward indole phytoalexins. The first synthesis of (±)-1-methoxyspirobrassinin, (±)-1-methoxyspirobrassinol, and (±)-1-methoxyspirobrassinol methyl ether , 2002 .

[30]  R. Stephani,et al.  Enantiomeric enrichment of non-racemic antihistamines by achiral high-performance liquid chromatography , 1998 .

[31]  Thomas J. Wenzel,et al.  Discrimination of Chiral Compounds Using NMR Spectroscopy , 2007 .

[32]  R. Sjöholm,et al.  Synthesis, characterisation and theoretical calculations of 2,6-diaminopurine etheno derivatives. , 2005, Organic & biomolecular chemistry.

[33]  J. Harborne.  The comparative biochemistry of phytoalexin induction in plants , 1999 .

[34]  Hermann Stoll,et al.  Results obtained with the correlation energy density functionals of becke and Lee, Yang and Parr , 1989 .

[35]  K. Monde,et al.  Spirobrassinin, a Novel Sulfur-containing Phytoalexin from the Daikon Rhaphanus sativus L. var. hortensis (Cruciferae) , 1987 .

[36]  V. Soloshonok,et al.  Remarkable amplification of the self-disproportionation of enantiomers on achiral-phase chromatography columns. , 2006, Angewandte Chemie.

[37]  M. Pedras,et al.  The Synthesis and Biosynthesis of Phytoalexins Produced by Cruciferous Plants , 2003 .

[38]  V. Soloshonok,et al.  Self-disproportionation of enantiomers of (R)-ethyl 3-(3,5-dinitrobenzamido)-4,4,4-trifluorobutanoate on achiral silica gel stationary phase , 2006 .

[39]  A. Collins,et al.  Cruciferous vegetables and colo-rectal cancer , 2006, Proceedings of the Nutrition Society.

[40]  M. Pedras,et al.  Determination of the enantiomeric purity of the phytoalexins spirobrassinins by 1H NMR using chiral solvation. , 2004, Bioorganic & medicinal chemistry letters.

[41]  Peter Pulay,et al.  Efficient implementation of the gauge-independent atomic orbital method for NMR chemical shift calculations , 1990 .

[42]  Parr,et al.  Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. , 1988, Physical review. B, Condensed matter.

[43]  M. Morbidelli,et al.  Measurement of the Dimerization Equilibrium Constants of Enantiomers , 2002 .

[44]  E. Kleinpeter,et al.  DFT computational studies of hydrogen bonding-based diastereomeric complexes - Limitations and applications to enantiodifferentiation , 2009 .

[45]  Peter Hänggi,et al.  Chiral separation in microflows. , 2005, Physical review letters.