Reinvestigation of the Absolute Configurations of Chiral β-Mercaptoalkanones Using Vibrational Circular Dichroism and ¹H NMR Analysis

Abstract

The absolute configurations of chiral β-mercaptoalkanones were previously assigned on the basis of the H NMR anisotropy method using (S)-2-methoxy-2-(1-naphthyl)propionic acid ((S)-MαNP) as the chiral auxiliary. This study presents a reinvestigation of the configurations of 4-mercapto-2-pentanone 1, 4-mercapto-2-heptanone 2, and 2-mercapto-4-heptanone 3. Enantiomers of 1, 2, and 3 were obtained by lipase-catalyzed hydrolyses of the respective acetylthioalkanones. Upon derivatization with (S)-MαNP, the configurations of the reaction products were deduced based on the order of the HPLC elution of the diastereoisomeric thioesters, assuming that the sector rule previously developed for secondary alcohols is also valid for thiols. In addition, the configurations were experimentally determined by vibrational circular dichroism (VCD) andH NMR analyses after esterification with (R)-hydratropic acid (HTA) and 2-methoxy-2-phenylacetic acid (MPA). The assignments of the configurations using VCD and NMR analyses of HTA- and MPA-thioesters were in agreement. However, they were opposite to those deduced for (S)-MαNP thioesters via the sector rule. Consequently, the formerly assigned configurations of β-mercaptoalkanones deduced via investigation of (S)-MαNP-derivatives have to be revised.

Analytical and Sensory Characterization of the Stereoisomers of 3-Mercaptocycloalkanones and 3-Mercaptocycloalkanols

“…1 H-detected experiments were done with an inverse 1 H/ 13 C probehead. Direct 13 C measurements were performed with a QNP 13 C/ 31 P/ 29 Si/ 19 F/ 1 H cryoprobe. The experiments were carried out in full automation using standard parameter sets of the TOPSPIN 3.0 software package (Bruker).…”

“…The experiments were carried out in full automation using standard parameter sets of the TOPSPIN 3.0 software package (Bruker). 13 C NMR spectra were recorded in the proton-decoupled mode. The spectra were recorded at 27 °C.…”

“…Among the volatile sulfur-containing constituents occurring in foods, − polyfunctional thiols are attractive flavor compounds with low odor thresholds and interesting odor properties. − A 1,3-oxygen sulfur functionality with a defined arrangement of substituents is considered as an essential structural feature constituting the so-called “tropical olfactophore”. , Several of these polyfunctional thiols are chiral; accordingly, studies on structure–odor relationships in homologous series increasingly take into consideration not only the chain lengths and the positions of the functional groups but also the impact of the configurations on the sensory properties. , An example of systematic investigations of these stereochemical aspects is the comparative assessment of the sensory properties of a homologous series of linear β-mercaptoalkanones and β-mercaptoalkanols. For the different positional isomers, the influence of the type and the spatial arrangements of the substituents at the stereogenic centers has been demonstrated. − …”

Analysis of Molecular Configuration and Conformation by (Electronic and) Vibrational Circular Dichroism: Theoretical Calculation and Exciton Chirality Method

“…These results suggested the absolute configuration of (¹)-3 to be R and its major conformations to be an equilibrated mixture of the conformers shown in Figure 3a. 20 This example demonstrated the difference between the prediction of the stable conformers of a given molecule and the validation of such prediction. Prediction itself can be carried out by theoretical calculations alone, but the use of VCD spectroscopy is capable of validating the calculated results.…”

“…Because of substantial enhancement of VCD signals, this strategy requires a lower sample amount, as exemplified in the studies of spiroindicumides A (20) and B (21). The VCD signals of 20 and 21 were relatively weak when measured at a concentration of 50 mM.…”