Site-Selective Dehydroxy-Chlorination of Secondary Alcohols in Unprotected Glycosides

To circumvent protecting groups, the site-selective modification of unprotected glycosides is intensively studied. We show that site-selective oxidation, followed by treatment of the corresponding trityl hydrazone with tert-butyl hypochlorite and a H atom donor provides an effective way to introduce a chloride substituent in a variety of mono- and disaccharides. The stereoselectivity can be steered, and a new geminal dichlorination reaction is described as well. This strategy challenges existing methods that lead to overchlorination

A Predictive Model for the Pd-Catalyzed Site-Selective Oxidation of Diols

A predictive model, shaped as a set of rules, is presented that predicts site-selectivity in the mono-oxidation of diols by palladium-neocuproine catalysis. For this, the factors that govern this site-selectivity within diols and between different diols have been studied both experimentally and with computation. It is shown that an electronegative substituent antiperiplanar to the C-H bond retards hydride abstraction, resulting in a lower reactivity. This explains the selective oxidation of axial hydroxy groups in vicinal cis-diols. Furthermore, DFT calculations and competition experiments show how the reaction rate of different diols is determined by their configuration and conformational freedom. The model has been validated by the oxidation of several complex natural products, including two steroids. From a synthesis perspective, the model predicts whether a natural product comprising multiple hydroxy groups is a suitable substrate for site-selective palladium-catalyzed oxidation.</p

Site-Selective Palladium-catalyzed Oxidation of Unprotected Aminoglycosides and Sugar Phosphates

The site-selective modification of complex biomolecules by transition metal-catalysis is highly warranted, but often thwarted by the presence of Lewis basic functional groups. This study demonstrates that protonation of amines and phosphates in carbohydrates circumvents catalyst inhibition in palladium-catalyzed site-selective oxidation. Both aminoglycosides and sugar phosphates, compound classes that up till now largely escaped direct modification, are oxidized with good efficiency. Site-selective oxidation of kanamycin and amikacin was used to prepare a set of 3'-modified aminoglycoside derivatives of which two showed promising activity against antibiotic-resistant E. coli strains.</p

Site-Selective Palladium-catalyzed Oxidation of Unprotected Aminoglycosides and Sugar Phosphates

The site-selective modification of complex biomolecules by transition metal-catalysis is highly warranted, but often thwarted by the presence of Lewis basic functional groups. This study demonstrates that protonation of amines and phosphates in carbohydrates circumvents catalyst inhibition in palladium-catalyzed site-selective oxidation. Both aminoglycosides and sugar phosphates, compound classes that up till now largely escaped direct modification, are oxidized with good efficiency. Site-selective oxidation of kanamycin and amikacin was used to prepare a set of 3'-modified aminoglycoside derivatives of which two showed promising activity against antibiotic-resistant E. coli strains.</p

CCDC 2158390: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 2158452: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 2158467: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 2158464: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 2158459: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 2158399: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures