The Deuterated "Magic Methyl" Group: A Guide to Site-Selective Trideuteromethyl Incorporation and Labeling by Using CD3 Reagents.

In the field of medicinal chemistry, the precise installation of a trideuteromethyl group is gaining ever-increasing attention. Site-selective incorporation of the deuterated "magic methyl" group can provide profound pharmacological benefits and can be considered an important tool for drug optimization and development. This review provides a structured overview, according to trideuteromethylation reagent, of currently established methods for site-selective trideuteromethylation of carbon atoms. In addition to CD3 , the selective introduction of CD2 H and CDH2 groups is also considered. For all methods, the corresponding mechanism and scope are discussed whenever reported. As such, this review can be a starting point for synthetic chemists to further advance trideuteromethylation methodologies. At the same time, this review aims to be a guide for medicinal chemists, offering them the available C-CD3 formation strategies for the preparation of new or modified drugs.

Phase-selective low molecular weight organogelators derived from allylated d-mannose.

In the last decades, synthesis and design of low molecular weight organogelators has gained increasing attention due to their versatile use in, for example, cosmetics, biomedicine and oil spill remediation. In this work, three potential gelators have been prepared from allylated d-mannose. Both the gelators and the corresponding gels formed were thoroughly characterized by crystallography, FTIR spectroscopy, SEM, rheometry and NMR spectroscopy, in solution and in solid state. The results showed that two of the compounds phase-selectively form gels with hydrocarbon solvents. The most promising gelator compound is alkene terminated, with the unsaturated end functionality not critical for gel formation, tentatively providing the possibility for customizing the gelation properties by further chemical modification. Alternatively, the alkene group could possibly be utilized as a linker for future coupling to carrier materials or surfaces to further increase the mechanical strength of the gel.

Improved synthesis and application of conjugation-amenable polyols from d-mannose.

A series of polyhydroxyl sulfides and triazoles was prepared by reacting allyl and propargyl d-mannose derivatives with selected thiols and azides in thiol-ene and Huisgen click reactions. Conformational analysis by NMR spectroscopy proved that the intrinsic rigidity and linear conformation of the mannose derived polyol backbone is retained in the final click products in solution. Single crystal X-ray structure determination of one of the compounds prepared further verified that the linear conformation of the polyol segment is also retained in the solid state. In addition, an improved method for direct Barbier-type propargylation of unprotected d-mannose is reported. The new reaction protocol, involving tin-mediated propargylation in an acetonitrile-water mixture, provides access to multigram quantities of the desired, valuable alkyne polyol without relying on protecting group manipulations or chromatographic purification.