Regiospecific Hydrogenation of Bromochalcone by Unconventional Yeast Strains.

This research aimed to select yeast strains capable of the biotransformation of selected 2'-hydroxybromochalcones. Small-scale biotransformations were carried out using four substrates obtained by chemical synthesis (2'-hydroxy-2″-bromochalcone, 2'-hydroxy-3″-bromochalcone, 2'-hydroxy-4″-bromochalcone and 2'-hydroxy-5'-bromochalcone) and eight strains of non-conventional yeasts. Screening allowed for the determination of the substrate specificity of selected microorganisms and the selection of biocatalysts that carried out the hydrogenation of tested compounds in the most effective way. It was found that the position of the bromine atom has a crucial influence on the degree of substrate conversion by the tested yeast strains. As a result of the biotransformation of the 2'-hydroxybromochalcones, the corresponding 2'-hydroxybromodihydrochalcones were obtained. The products obtained belong to the group of compounds with high potential as precursors of sweet substances.

Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions.

The purpose of this review is to highlight the necessity of conducting tests to gauge the magnitude of the self-disproportionation of enantiomers (SDE) phenomenon to ensure the veracity of reported enantiomeric excess (ee) values for scalemic samples obtained from enantioselective reactions, natural products isolation, etc. The SDE always occurs to some degree whenever any scalemic sample is subjected to physicochemical processes concomitant with the fractionation of the sample, thus leading to erroneous reporting of the true ee of the sample if due care is not taken to either preclude the effects of the SDE by measurement of the ee prior to the application of physicochemical processes, suppressing the SDE, or evaluating all obtained fractions of the sample. Or even avoiding fractionation altogether if possible. There is a clear necessity to conduct tests to assess the magnitude of the SDE for the processes applied to samples and the updated and improved recommendations described herein cover chromatography and processes involving gas-phase transformations such as evaporation or sublimation.

The self-disproportionation of enantiomers (SDE) via column chromatography of ß-amino-α,α-difluorophosphonic acid derivatives.

This work presents the first study of the self-disproportionation of enantiomers via chromatography (SDEvC) of ß-aminophosphonic acid esters, several of which have been synthesized for the first time. Three types of structures were examined, N-acetylated, dipeptide construction with N-Cbz glycine, and a free amine. In the latter case, this is the first time that SDEvC has been reported for free amine amino acids. In all the three types of structures, significant SDE magnitudes (Δee's up to 55%) were exhibited underscoring the ubiquitous nature of the SDE phenomenon. Chemical models of homo- versus heterochiral intermolecular interactions are proposed to rationalize the SDE magnitude differences amongst these new ß-aminophosphonic acid derivatives. In addition, the incorporation of additional, competing binding modes to a molecule, was found to lead to a reduction of the SDE magnitude by shifting the intermolecular binding away from the stereogenic center and/or by leading to a convoluted binding system that disrupts the structured and relatively stable assemblies that give rise to the SDE.

The self-disproportionation of enantiomers (SDE) of amino acids and their derivatives.

This review covers the phenomenon of the self-disproportionation of enantiomers (SDE) of amino acids and their derivatives in all its guises from phase transformations (recrystallization, sublimation, and distillation), to the application of force fields, through to chromatography including HPLC, MPLC, gravity-driven column chromatography, and SEC. The relevance of the SDE phenomenon to amino acid research and to marketed pharmaceuticals is clear given the potential for alteration of the enantiomeric excess of a portion of a scalemic sample. In addition, the possible contribution of the SDE phenomenon to the genesis of prebiotic homochirality is considered.

The self-disproportionation of enantiomers (SDE): The effect of scaling down, potential problems versus prospective applications, possible new occurrences, and unrealized opportunities?

This commentary discusses an important, though not widely appreciated, chiral phenomenon of molecular chirality that effectively always occurs whenever nonracemic samples are subjected to practically any physicochemical process (e.g., force field, recrystallization, sublimation, even distillation, etc.) under totally achiral conditions external to the sample itself. The phenomenon is termed as the self-disproportionation of enantiomers (SDE) and though ubiquitous, its presence may not always be readily apparent, or workers may be otherwise oblivious to its effects. In the particular case of chromatography, when the SDE is apparent, the enantiomeric excess (ee) of the chiral compound is observed to vary across an eluted peak, with anterior eluted portions either enantioenriched or enantiodepleted relative to the ee of the starting material, and conversely for the posterior eluted portions. Herein, we highlight various aspects of the SDE phenomenon as it pertains to chromatography and, in particular, the effect of scaling down chromatographic systems, the potential risk of problems that the SDE can cause, as well as opportunities for practical applications of the phenomenon, possible new occurrences of the SDE phenomenon to be searched for, and unrealized opportunities.

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

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.

Internal chirality descriptors iR and iS and ire and isi. A proposed notation to extend the usefulness of the R/S system by retaining the sense of stereochemistry in cases of ligand ranking changes.

The R/S system, universally applied for indicating the absolute configuration of a structure, is extremely adept for conveying the absolute configuration unequivocally. However, it suffers from one limitation, viz that due to CIP priority rules the rankings of the ligands attached to an asymmetric center can be altered upon a change in a ligand leading to a change in the designated configuration even if bonds to the asymmetric center were not actually formed or broken. This means that the sense of stereochemistry in situations such as within a set of compounds where family relationships are of focus or where the sense of the stereochemical course of a reaction is of interest can be lost or confusion may occur. This shortcoming is easily remedied though by defining a fixed ranking for a particular ligand in the system under study, eg, the ligand at which the change has occurred. The configurations are then expressed as iR or iS, akin to the R and S descriptors, for sp3 -hybridized tetrahedral chiral structures and similarly, as ire and isi faces, akin to the re and si descriptors, for sp2 -hybridized trigonal prochiral structures. All in all, the notation can be considered as an auxiliary to extend the usefulness of the R/S system. Thus, the proposed iR/iS notation could find profitable use in comparative studies where there is a need to avoid confusion arising from changing assignments due to priority rules or to expedite the ease of comprehension. Moreover, in the current digital age, the facile retrieval of stereochemically clear data by machines is highly desirable-something that the iR/iS notation is readily amenable to.

The self-disproportionation of enantiomers (SDE): a menace or an opportunity?

Herein we report on the well-documented, yet not widely known, phenomenon of the self-disproportionation of enantiomers (SDE): the spontaneous fractionation of scalemic material into enantioenriched and -depleted fractions when any physicochemical process is applied. The SDE has implications ranging from the origins of prebiotic homochirality to unconventional enantiopurification methods, though the risks of altering the enantiomeric excess (ee) unintentionally, regrettably, remain greatly unappreciated. While recrystallization is well known as an SDE process, occurrences of the SDE in other processes are much less recognized, e.g. sublimation and even distillation. But the most common process that many workers seem to be completely ignorant of is SDE via chromatography and reports have included all manner of structures, all types of interactions, and all forms of chromatography, including GC. The SDE can be either a blessing - as a means to obtain enantiopure samples from scalemates - or a curse, as unwitting alteration of the ee leads to errors in the reporting of results and/or misinterpretation of the system under study. Thus the ramifications of the SDE are relevant to any area involving chirality - natural products, asymmetric synthesis, etc. Moreover, there is grave concern regarding errors in the literature, in addition to the possible occurrence of valid results which may have been overlooked and thus remain unreported, as well as the potential for the SDE to alter the ee, particularly via chromatography, and the following concepts will be conveyed: (1) the SDE occurs under totally achiral conditions of (a) precipitation, (b) centrifugation, (c) evaporation, (d) distillation, (e) crystallization, (f) sublimation, and (g) achiral chromatography (e.g. column, flash, MPLC, HPLC, SEC, GC, etc.). (2) The SDE cannot be controlled simply by experimental accuracy and ignorance of the SDE unavoidably leads to mistakes in the recorded and reported stereochemical outcome of enantioselective transformations. (3) The magnitude of the SDE (the difference between the extremes of enantioenrichment and -depletion) can be controlled and used to: (a) minimize mistakes in the recorded experimental values and (b) to develop unconventional and preparatively superior methods for enantiopurification. (4) The magnitude of the SDE cannot be predicted but can be expected for compounds possessing SDE-phoric groups or which have a general tendency for strong hydrogen or halogen bonds or dipole-dipole or aromatic π-π interactions. (5) An SDE test and the rigorous reporting and description of applied physicochemical processes should become part of standard experimental practice to prevent the erroneous reporting of the stereochemical outcome of enantioselective catalytic reactions and the chirooptical properties of scalemates. New directions in the study of the SDE, including halogen bonding-based interactions and novel, unconventional enantiopurification methods such as pseudo-SDE (chiral selector-assisted SDE resolution of racemates), are also reported.

Chiral sulfoxides: advances in asymmetric synthesis and problems with the accurate determination of the stereochemical outcome.

Chiral sulfoxides are in extremely high demand in nearly every sector of the chemical industry concerned with the design and development of new synthetic reagents, drugs, and functional materials. The primary objective of this review is to update readers on the latest developments from the past five years (2011-2016) in the preparation of optically active sulfoxides. Methodologies covered include catalytic asymmetric sulfoxidation using either chemical, enzymatic, or hybrid biocatalytic means; kinetic resolution involving oxidation to sulfones, reduction to sulfides, modification of side chains, and imidation to sulfoximines; as well as various other methods including nucleophilic displacement at the sulfur atom for the desymmetrization of achiral sulfoxides, enantioselective recognition and separation based on either metal-organic frameworks (MOF's) or host-guest chemistry, and the Horner-Wadsworth-Emmons reaction. A second goal of this work concerns a critical discussion of the problem of the accurate determination of the stereochemical outcome of a reaction due to the self-disproportionation of enantiomers (SDE) phenomenon, particularly as it relates to chiral sulfoxides. The SDE is a little-appreciated phenomenon that can readily and spontaneously occur for scalemic samples when subjected to practically any physicochemical process. It has now been unequivocally demonstrated that ignorance in the SDE phenomenon inevitably leads to erroneous interpretation of the stereochemical outcome of catalytic enantioselective reactions, in particular, for the synthesis of chiral sulfoxides. It is hoped that this two-pronged approach to covering the chemistry of chiral sulfoxides will be appealing, engaging, and motivating for current research-active authors to respond to in their future publications in this exciting area of current research.

Possible Case of Halogen Bond-Driven Self-Disproportionation of Enantiomers (SDE) via Achiral Chromatography.

The major breakthrough reported in this work is the discovery of likely halogen bond-driven self-disproportionation of enantiomers (SDE). Taking into account that the halogen-bonding interactions can be rationally designed and can match, or even exceed, the strength of the more familiar hydrogen bond, this discovery clearly opens an unexpected new direction of research in the areas of molecular chirality and the SDE phenomenon.

Diastereoselective α-Alkylation of Metallo Enamines Generated from N-C Axially Chiral Mebroqualone Derivatives.

The reactions of various alkyl halides with the metallo enamines generated from racemic and optically pure N-C axially chiral mebroqualone derivatives were found to proceed with a synthetically attractive stereochemical outcome (up to 99% yield and up to dr = 26:1) allowing preparation of a structurally new type of pharmaceutically interesting compounds possessing elements of axial and central chirality.

Self-disproportionation of enantiomers via achiral gravity-driven column chromatography: A case study of N-acyl-α-phenylethylamines.

Herein we report a study of the self-disproportionation of enantiomers (SDE) via gravity-driven achiral column chromatography of a series of amides derived from 1-phenylethylamine. We demonstrated that structural and electronic factors of the substituents play an important role in the observed magnitude of the SDE. For the first time, the SDE phenomenon of amides with that of thioamides was compared. We demonstrate that, in sharp contrast to amides, the substitution of the sulphur atom for the oxygen in the acyl group, strongly reduced the observed magnitude of the SDE. These results clearly indicate the importance of the hydrogen bonding for the formation of homo/hetero-chiral association responsible for manifestation of the SDE phenomenon.

Remarkable magnitude of the self-disproportionation of enantiomers (SDE) via achiral chromatography: application to the practical-scale enantiopurification of ß-amino acid esters.

We report the best performance yet for the self-disproportionation of enantiomers (SDE) via achiral chromatography as typically used in laboratories for the isolated yield of the excess enantiomer using N-acetyl ß-amino acid ethyl esters. The results are the most convincing ever demonstration of the capability of the SDE for practical-scale enantiopurification as comparable, or even superior for some systems, to that of recrystallization. For example, from a sample of 94.4 % ee, a yield of 71 % of enantiopure material was isolated in a single chromatographic run. Moreover, the lack of an esoteric structural entity, e.g. strongly polarizing groups, such as, for instance CF3, highlights the fact that the phenomenon is not dependent on the presence of such and thus the process is relevant to any usual-type structure. In contrast to recrystallization, the procedure is predictable, general, and dependable, boding well for its widespread application in routine laboratory settings.

Introducing a new radical trifluoromethylation reagent.

Perfluoro-3-ethyl-2,4-dimethyl-3-pentyl radical (PPFR) is a persistent radical stable at room temperature, but easily decomposes at 90 °C to produce a CF3 radical which is able to react with a variety of aromatic compounds to afford the corresponding trifluoromethyl derivatives, usually as mixtures of regioisomers in good to excellent overall yields.

Synthesis and complexing properties of diglycol resorcinarene podands.

Synthesis of new podands from resorcinarene and diethylene glycols are reported. The binding properties of these podands with alkali metal cations was studied by means of ESI-MS. The experimental results for podands with long diethylene glycol arms show the stable inclusion complexes with one or two metal cations and high affinity for sodium and potassium ions. This podands under appropriate conditions can thus form a sufficiently long cavity to accommodate more than one metal ion inside without disturbance of the axial symmetry like an ion channel. Podand with shorter arms, obtained from ethylene glycol form complexes with 1:1 stoichiometry and also readily dimers or trimers. In the presence of alkali metal cations this podand selectively binds cesium ions. The significant affinity of synthesized podands for the biologically important alkali metal ions may affect living organisms. Antibacterial activities were tested with series of Gram-positive and Gram-negative bacteria.

The self-disproportionation of the enantiomers (SDE) of methyl n-pentyl sulfoxide via achiral, gravity-driven column chromatography: a case study.

This work explores the self-disproportionation of enantiomers (SDE) of chiral sulfoxides via achiral, gravity-driven column chromatography using methyl n-pentyl sulfoxide as a case study. A major finding of this work is the remarkable persistence and high magnitude of the SDE for the analyte. Thus, it is the first case where SDE is observed even in the presence of MeOH in the mobile phase. The study demonstrated the practical preparation, in line with theory, of enantiomerically pure (>99.9% ee) samples of methyl n-pentyl sulfoxide starting from a sample of only modest ee (<35%). Remarkably, it was found that the order of elution was inverted, i.e. enantiomerically depleted fractions preceded later eluting enantiomerically enriched ones, when the stationary phase was changed from silica gel to aluminum oxide. To the best of our knowledge, this is the first occurrence of inverted SDE behavior due solely to a change in the stationary phase. Aberrant SDE behavior was observed in that the ee did not always fall continuously during the progression of the chromatography, and this was attributed to the complexity of the system at hand which cannot be described in simple terms such as the formation only of homo- and heterochiral dimers based on a single interaction. The results nevertheless suggest that all compounds with a chiral sulfoxide moiety in their structure are likely to exhibit the SDE phenomenon and thus this work constitutes the first example of SDE predictability. Moreover, it could well be that optical purification based on the SDE phenomenon is a simple, convenient, and inexpensive method for the optical purification of this class of compounds with a high degree of proficiency.

Optical purifications via self-disproportionation of enantiomers by achiral chromatography: case study of a series of α-CF3-containing secondary alcohols.

This work demonstrates that self-disproportionation of enantiomers via achiral chromatography can be recommended as inexpensive and general method for optical purification of enantiomerically enriched compounds. In particular, the advantage of this approach over conventional recrystallization is that it can be used for both crystalline as well as liquid compounds.