Entropic-Based Separation of Diastereomers: Size-Exclusion Chromatography with Online Viscometry and Refractometry Detection for Analysis of Blends of Mannose and Galactose Methyl-α-pyranosides at “Ideal” Size-Exclusion Conditions

The separation of carbohydrate diastereomers by an ideal size-exclusion mechanism, i.e., in the absence of enthalpic contributions to the separation, can be considered one of the grand challenges in chromatography: Can a difference in the location of a single axial hydroxy group on a pyranose ring (e.g., the axial OH being located on carbon 2 versus on carbon 4 of the ring) sufficiently affect the solution conformational entropy of a monosaccharide in a manner which allows for members of a diastereomeric pair to be separated from each other by size-exclusion chromatography (SEC)? Previous attempts at answering this question, for aqueous solutions, have been thwarted by the mutarotation of sugars in water. Here, the matter is addressed by employing the non-mutarotating methyl-α-pyranosides of d-mannose and d-galactose. We show for the first time, using SEC columns, the entropically driven separation of members of this diastereomeric pair, at a resolution of 1.2–1.3 and with only a 0.4–1% change in solute distribution coefficient over a 25 °C range, thereby demonstrating the ideality of the separation. It is also shown how the newest generation of online viscometer allows for improved sensitivity, thereby extending the range of this so-called molar-mass-sensitive detector into the monomeric regime. Detector multidimensionality is showcased via the synergism of online viscometry and refractometry, which combine to measure the intrinsic viscosity and viscometric radius of the sugars continually across the elution profiles of each diastereomer, methyl-α-d-mannopyranoside and methyl-α-d-galactopyranoside.

Different Strategies for Obtaining Enantiopure Hemicryptophanes

Hemicryptophanes have recently emerged as an attractive class of cages due to their interesting applications as supramolecular receptors and catalysts. Over the last decade, substantial advances have been made regarding the preparation of enantiopure versions of these synthetic receptors. Enantiopure hemicryptophanes are commonly obtained through the separation of diastereomers by chromatography, or by resolution of racemic mixtures using chiral HPLC. This short review summarizes the existing methods to access to these chiral organic architectures and discusses the benefits and drawbacks of each approach.1 Introduction2 Enantiopure Hemicryptophanes Obtained by Introducing Additional Chiral Units and Separation of Diastereomers2.1 Synthesis by Means of Intramolecular Macrocyclization Reactions2.2 [1+1] Coupling of the CTV and the Southern Part3 Enantiopure Hemicryptophanes Obtained by Means of Chiral HPLC Resolution of Enantiomers3.1 Resolution of Hemicryptophane Racemates3.2 Resolution of CTV-Based Precursor Racemates4 Conclusion

Chiral separation of diastereomers of the cyclic nonapeptides vasopressin and desmopressin by uniform field ion mobility mass spectrometry

In this study ion mobility-mass spectrometry (IM-MS) is used to distinguish chiral diastereomers of the nonapeptides desmopressin and vasopressin.

Total Synthesis of Eleuthoside A; Application of Rh-Catalyzed Intramolecular Cyclization of Diazonaphthoquinone

The first total synthesis of (±)-eleutherol and eleuthoside A, the natural cytotoxic substances extracted from medicinal Indonesian plant, is described. First, the synthesis of (±)-eleutherol has been ­accomplished in nine steps starting from bromo methoxy aldehyde with the aid of diazo-transfer chemistry approach. Second, a metal-­catalyzed intramolecular cyclization reaction of the corresponding ­diazonaphthoquinone led to the desired eleuotherol, which served as a precursor to eleuthoside A. Then, several glycosidation routes, using different glucosyl donors, were experimented to reach effective O-glycosidation of eleutherol. The only successful strategy involved Koenigs–Knorr glycosidation using peracetyl glycosyl bromide in the presence of Ag2O and quinoline. This strategy furnished our desired acetylated glycoside of β-configuration, regioselectively. Finally, deacetylation and successive separation of diastereomers were conducted to give eleuthoside A.