Christie Aroulanda

Investigation of SmI2-mediated cyclisation of δ-iodo-α,β-unsaturated esters by deuterium 2D NMR in oriented solvents

Abstract We have investigated the mechanism of the SmI 2 -mediated cyclisation of δ-iodo-α,β-unsaturated esters using proton-decoupled deuterium 1D and 2D NMR in weakly ordered polypeptide liquid crystal solvents. Analysis of the spectroscopic results demonstrates that the cyclisation reaction takes place with concomitant and extensive racemisation at the γ-position and the reason for this racemisation is discussed. We also report an efficient 2D NMR strategy for distinguishing meso - from d - and l -diastereoisomers based on the introduction of a CD 2 probe in the molecules to be studied. This approach allows determination of the diastereoisomeric and enantiomeric composition of a mixture.

Efficient enantiodiscrimination of chiral monophosphine oxides and boranes by phosphorus coupled 13C NMR spectroscopy in the presence of chiral ordering agents

Abstract The synthesis of new chiral phospholanes via the corresponding oxides or boranes is reported and the analytical potential of 13 C-{ 1 H} NMR spectroscopy in weakly ordering polypeptide liquid crystalline phases in view to differentiate between enantiomers of these chiral phosphines precursors is explored. In particular results involving organic solutions of poly-γ-benzyl- l -glutamate (PBLG) and poly-e-carbobenzyloxy- l -lysine (PCBLL) are described. This NMR approach allows determination of the enantiomeric composition, and provides therefore a new efficient alternative to classical methods usually used to analyze this class of compounds. A description of various spectral enantiodifferentiation patterns expected to be observed using 13 C-{ 1 H} NMR of enantiomers having a spin-1/2 heteroatomic nucleus, embedded in a chiral liquid crystal is presented.

GET-SERF, a new gradient encoded SERF experiment for the trivial edition of 1H-19F couplings.

A new spatially encoded heteronuclear (1)H-(19)F selective refocusing NMR experiment (GET-SERF) is proposed. This sequence allows editing in one single 2D experiment all couplings between a selected fluorine site and all the proton nuclei of the molecule. Its efficiency is illustrated in the case of diflunisal, a difluorinated anti-inflammatory drug, in isotropic and anisotropic media.

Enantiomeric recognition of chiral invertomers through NMR in chiral oriented phases: a study of cis-decalin

Abstract We describe a deuterium 1D and 2D NMR study of cis -decalin in various chiral and achiral polypeptide oriented solvent systems and the effect of the acquisition temperature. Organic solutions of poly-γ-benzyl- l -glutamate (PBLG) or poly-e-carbobenzyloxy- l -lysine (PCBLL) in dichloromethane or chloroform allow the chiral invertomers of cis- decalin to be differentiated at low temperature. At high temperature, it is possible to distinguish between deuterium nuclei of the molecule which become enantiotopic under rapid kinetic averaging. The results obtained illustrate the capability of such polypeptide liquid-crystalline solvents to enantioselectively interact with unfunctionalised chiral cycloalkanes and highlight the analytical potential of NMR analysis in chiral liquid crystal based solvents in the investigation of interconverting chiral conformers.

Analytical contribution of NAD 2D-NMR spectroscopy in polypeptide mesophases to the investigation of triglycerides: NMR analysis of triglycerides

In this work, we report and discuss on the use and limitations of the natural abundance deuterium two‐dimensional NMR spectroscopy in polypeptide chiral and achiral aligning media in the studies of homogenous triglycerides at 14.1 T. As illustrative examples, two triglycerides with short and long alkyl chains were investigated: the 1,3‐di(butanoyloxy)propan‐2‐yl butanoate or tributyrin (TB) and the 1,3‐di(tetradecanoyloxy)propan‐2‐yl tetradecanoate or trimyristin (TM). If both flexible compounds are theoretically of Cs symmetry on average, according to the Altmanns definition (Proc. Roy. Soc., 1967, A298, 184.), the analysis of spectral data in terms of enantiotopic and diastereotopic discriminations shows noticeable differences related to their orientational ordering behavior inside the mesophases. Although from NMR analysis viewpoint, TB behaves as a Cs symmetry molecule as expected, the NMR results obtained for TM suggest a behavior that could be formally predicted for a C3v symmetry molecule on average. This conclusion was nicely supported by the comparison with the tri‐n‐propylorthoformate, a real C3v symmetry solute on average on the NMR timescale. This difference of effective orientational behavior could originate from the difference of size and shape between lateral and central alkyl chains of the solute molecule. Copyright

Evolution of the Saupe order parameters of enantiomers from a racemic to a non-racemic liquid crystal solvent: an original light on the absolute configuration determination problem

Chiral liquid crystals used as solvents have been shown to be very powerful in giving separate nuclear magnetic resonance (NMR) signals for enantiomers. However, a fundamental problem remains: how to attribute absolute configurations to the various NMR responses? In this paper it is demonstrated that the absolute configuration problem could be solved in predicting the sign of the rotation of the principal axis system of the Saupe matrix in the molecular frame when going from an achiral (racemic) to a chiral anisotropic solvent.

The conformational behaviour of naproxen and flurbiprofen in solution by NMR spectroscopy

Naproxen and flurbiprofen are among the most popular and widely used drugs for treating pain and inflammation and new different therapeutic uses are still being proposed. Their pharmacological activity comes from the specific binding to target proteins and is evidently driven by the spatial arrangement they adopt at the active sites. A detailed conformational elucidation analysis in solution able to probe equilibria between more possible conformers is then crucial for understanding and rationalizing their biological role and possibly for designing improved analogues. Here we combine NMR data obtained in weakly ordered media and suitable theoretical models to look for the energetically admissible conformers of these two anti-inflammatory drugs in a liquid medium. This approach leads to rather complex probability distributions characterized for both molecules by an equilibrium of different global and local minimum energy structures.

NMR discrimination in nonrigid prochiral solutes dissolved in chiral liquid crystals: symmetry considerations.

Enantiodiscrimination in the NMR spectra of flexible prochiral solutes dissolved in chiral liquid crystals (CLCs) is reviewed and compared with the analog phenomenon in such rigid solutes. In rigid prochiral solutes, the discrimination is brought about by the cancellation of improper symmetry elements upon dissolving in CLC within the frame of solute‐solvent ordering mechanisms. If this reduction in symmetry renders the ordering of enantiotopic sites dissimilar, spectral discrimination may be observed. Symmetry considerations indicate that this is only possible for improper nonaxial groups lacking inversion symmetry. Nonrigid prochiral solutes consist of rapidly (on the NMR timescale) interconverting enantiomers, in which the racemization is accompanied by exchange of nonequivalent sites. These sites become, on the average, enantiotopically related, and in CLC, they exhibit spectral discrimination. The mechanism of the effect and the symmetry selection rules are different for the two cases. Specifically, the discrimination in flexible prochiral compounds results from the different ordering of the interchanging enantiomers in CLC. Using Altmans definition of average symmetry (Proc. R. Soc. A, 1967, 298, 184), selection rules for the phenomenon are derived. It follows that chiral discrimination in nonrigid prochiral solutes is much more abundant and can occur in all symmetry types except those possessing inversion. In particular, contrary to earlier thoughts, the effect can occur in compounds with axial symmetry. Illustrative examples of such studies with particular emphasis on compounds with average axial symmetry of the type D3h, C3v and C3h are reviewed in this contribution. Copyright

Conformational and Orientational Determination from Dipolar Couplings in a Weakly Ordering Organic-Based Lyotropic and a Strongly Ordering Thermotropic Liquid Crystal

A weakly ordering organic-based lyotropic phase and a strongly ordering nematic liquid crystal have been used as NMR media for a parallel study of the conformation and orientational order of the same solute, trans-stilbene. A careful comparison allows to figure out some interesting conclusions on accessibility and precision of the experimental data and reliability and accuracy of the conformational descriptions into these two kinds of mesophases.