Determination of Interconversion Barriers by Dynamic Gas Chromatography: Epimerization of Chalcogran

Abstract

The four stereoisomers of chalcogran 1 ((2RS,SRS)-2-ethyl-1,6-di-oxaspiro[4.4]nonane), the principal component of the aggregation pheromone of the bark beetle pityogenes chalcographus, are prone to interconversion at the spiro center (C5). During diastereo- and enantioselective dynamic gas chromatography (DGC), epimerization of 1 gives rise to two independent interconversion peak profiles, each featuring a plateau between the peaks of the interconverting epimers. To determine the rate constants of epimerization by dynamic gas chromatography (DGC), equations to simulate the complex elution profiles were derived, using the theoretical plate model and the stochastic model of the chromatographic process. The Eyring activation parameters of the experimental interconversion profiles, between 70 and 120 C in the presence of the chiral stationary phase (CSP) Chirasil-beta-Dex, were then determined by computer-aided simulation with the aid of the new program Chrom-Win: (2R,5R)-1: deltaG(++) (298.15 K) = 108.0 +/-0.5 kJ mol(-1), deltaH(++) = 47.1+/-0.2 kJ mol(-1), deltaS(++) = -204+/-6 JK(-1) mol(-1): (2R,5S)-1: deltaG(++) (298.15 K) = 108.5+/-0.5 kJ mol(-1), deltaH(++) = 45.8+/-0.2 kJ mol(-1), deltaS(++) = -210 +/-6 J K mol(-1); (2S,5S)-1: deltaG(++) (298.15 K)= 108.1+/-0.5 kJ mol(-1), deltaH(++) = 49.3+/-0.3 kJ mol(-1), deltaS(++) = -197+/-8 J K(-1) mol(-1); (2S,5R)-1: deltaG(++) (298.15 K)=108.6+/-0.5 kJ mol(-1), deltaH(++) = 48.0+/-0.3 kJ mol(-1), deltaS(++) = -203+/-8 J K(-1) mol(-1). The thermodynamic Gibbs free energy of the E/Z equilibrium of the epimers was determined by the stopped-flow multidimensional gas chromatographic technique: deltaG(E/Z) (298.15 K)= -0.5 kJ mol(-1), deltaH(E/Z) = 1.4 kJ mol(-1) and deltaS(E/Z) = 6.3 J K(-1) mol(-1). An interconversion pathway proceeding through ring-opening and formation of a zwitterion and an enol ether/alcohol intermediate of 1 is proposed.

Determination of thecis-trans isomerization barrier of severalL-peptidyl-L-proline dipeptides by dynamic capillary electrophoresis and computer simulation

“…Dynamic chromatography, a method that allows the study of reversible interconversion processes proceeding during the time scale of partitioning, has previously been applied for the determination of enantiomerization barriers [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Recently, we extended the scope of applications in enantioselective dynamic chromatography by deriving equations to treat epimerization and isomerization processes in the presence of a chiral stationary phase with the theoretical plate model and the stochastic model [21][22][23]. Hence, the presented method may also be employed for many pending problems in dynamic chromatographic experiments like E/Zisomerism of hydrazones, imines and oximes [24,25] phenanthrene derivatives [26], and stereoisomerism of organic metal complexes [27,28], etc.…”

A Stereodynamic Redox‐Interconversion Network of Vicinal Tertiary and Quaternary Carbon Stereocenters in Hydroquinone–Quinone Hybrid Dihydrobenzofurans

“…We hypothesized that a two-stereocenter dihydrobenzofuran (Figure 2), which, in addition, is a spiro compound, [27] could be designed that allows for the separate study of reversible Michael-type addition and intramolecular redox-exchange in a four-state stereodynamic network. Along with our aim for phenomenological and mechanistic insights, dihydrobenzofuran model compounds also provide the opportunity to demonstrate epimerization of a quaternary carbon stereocenter without achiral intermediates.…”

Investigation of the enantiomerization barriers of the phthalimidone derivatives EM12 and lenalidomide by dynamic electrokinetic chromatography

“…In recent years, enantioselective dynamic chromatographic and electrophoretic techniques [22][23][24][25][26][27][28] in combination with fast and efficient evaluation tools have proven to be highly precise in the determination of enantiomerization barriers [29][30][31][32][33][34] of chiral drugs with enantiomerization barriers greater than 75 kJ/mol [35][36][37][38][39][40][41][42][43][44][45][46][47]. The advantage of these techniques is that only minute amounts of the racemic sample are required and can be applied in combination with any separation technique that yields a separation of the desired enantiomeric species as dynamic HPLC (DHPLC) [41,[48][49][50][51][52][53][54][55][56], dynamic GC (DGC) [42,46,[57][58][59][60][61][62], and dynamic CE (DCE) [43][44...…”