The present review is devoted to summarizing the recent advances (2015-2017) in the field of metal-catalysed group-directed C-H functionalisation In order to clearly showcase the molecular diversity that can now be accessed by means of directed C-H functionalisation, the whole is organized following the directing groups installed on a substrate Its aim is to be a comprehensive reference work, where a specific directing group can be easily found, together with the transformations which have been carried out with it Hence, the primary format of this review is schemes accompanied with a concise explanatory text, in which the directing groups are ordered in sections according to their chemical structure The schemes feature typical substrates used, the products obtained as well as the required reaction conditions Importantly, each example is commented on with respect to the most important positive features and drawbacks, on aspects such as selectivity, substrate scope, reaction conditions, directing group removal, and greenness The targeted readership are both experts in the field of C-H functionalisation chemistry (to provide a comprehensive overview of the progress made in the last years) and, even more so, all organic chemists who want to introduce the C-H functionalisation way of thinking for a design of straightforward, efficient and step-economic synthetic routes towards molecules of interest to them Accordingly, this review should be of particular interest also for scientists from industrial R&D sector Hence, the overall goal of this review is to promote the application of C-H functionalisation reactions outside the research groups dedicated to method development and establishing it as a valuable reaction archetype in contemporary R&D, comparable to the role cross-coupling reactions play to date

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A comprehensive overview of directing groups applied in metal-catalysed C-H functionalisation chemistry.

O.B. thanks the European Commission (Marie Curie CIG) and Ministerio de Ciencia e Innovacion, Spain (Juan de la Cierva Fellowship). G.J.L.B. thanks his generous sources of funding: Royal Society, FCT Portugal (FCT Investigator), European Commission (Marie Curie CIG), and the EPSRC. G.J.L.B. is a Royal Society University Research Fellow. The authors thank Paula Boutureira Regla and Francisco Pinteus da Cruz Lopes Bernardes for inspiration.

Advances in Chemical Protein Modification

Chemical modification of proteins is an important tool for probing natural systems, creating therapeutic conjugates and generating novel protein constructs. Site-selective reactions require exquisite control over both chemo- and regioselectivity, under ambient, aqueous conditions. There are now various methods for achieving selective modification of both natural and unnatural amino acids--each with merits and limitations--providing a 'toolkit' that until 20 years ago was largely limited to reactions at nucleophilic cysteine and lysine residues. If applied in a biologically benign manner, this chemistry could form the basis of true Synthetic Biology.

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Selective chemical protein modification

Increased understanding of the important roles that oligosaccharides and glycoconjugates play in biological processes has led to a demand for significant amounts of these materials for biological, medicinal, and pharmacological studies. Therefore, tremendous effort has been made to develop new procedures for the synthesis of glycosides, whereby the main focus is often the formation of the glycosidic bonds. Accordingly, quite a few review articles have been published over the past few years on glycoside synthesis; however, most are confined to either a specific type of glycoside or a specific strategy for glycoside synthesis. In this Review, new principles for the formation of glycoside bonds are discussed. Developments, mainly in the last ten years, that have led to significant advances in oligosaccharide and glycoconjugate synthesis have been compiled and are evaluated.

New principles for glycoside-bond formation.

Hydrogen sulfide (H2S) is emerging as an important mediator of human physiology and pathology but remains difficult to study, in large part because of the lack of methods for selective monitoring of this small signaling molecule in live biological specimens. We now report a pair of new reaction-based fluorescent probes for selective imaging of H2S in living cells that exploit the H2S-mediated reduction of azides to fluorescent amines. Sulfidefluor-1 (SF1) and Sulfidefluor-2 (SF2) respond to H2S by a turn-on fluorescence signal enhancement and display high selectivity for H2S over other biologically relevant reactive sulfur, oxygen, and nitrogen species. In addition, SF1 and SF2 can be used to detect H2S in both water and live cells, providing a potentially powerful approach for probing H2S chemistry in biological systems.

Reaction-based fluorescent probes for selective imaging of hydrogen sulfide in living cells.

The reactivity of a number of p-methylphenyl thioglycoside (STol) donors which are either fully protected or have one hydroxyl group exposed has been quantitatively determined by HPLC in conjunction with the development of a broadly applicable approach for a facile one-pot synthesis of oligosaccharides. The influence on reactivity of the structural effects of different monosaccharide cores and different protecting groups on each glycoside donor is characterized and quantified. In addition, a correlation between glycosyl donor reactivity and the chemical shift of the anomeric proton by 1 H NMR has been established. A database of thioglycosides as glycosyl donors has been created using this reactivity data. The utility is demonstrated by the easy and rapid one-pot assembly of various linear and branched oligosaccharide structures. In addition, a computer program as been described for use as a database search tool and guide for the selection of building blocks for the one-pot assembly of a desired oligosaccharide or a library of individual oligosaccharides.

Programmable one-pot oligosaccharide synthesis

Iterative One‐Pot Synthesis of Oligosaccharides

Programmable One‐Pot Oligosaccharide Synthesis.

Two efficient routes for the rapid assembly of the tumor-associated carbohydrate antigen Globo-H hexasaccharide 2 by a preactivation based iterative one-pot strategy are reported. The first method involves the sequential coupling of four glycosyl building blocks, leading to the desired hexasaccharide in 47% overall yield in one-pot synthesis. Although model studies on constructing the challenging Gal-α-(1−4)-Gal linkage in Gb3 trisaccharide yielded the desired α linkage almost exclusively, a similar approach to assemble the hexasaccharide led to the formation of a significant amount of β anomer. As an alternative, the second synthesis utilized three components in one pot with the Gal-α-(1−4)-Gal linkage preformed, producing the desired hexasaccharide in a similar overall yield as the four component approach. Both methods demonstrate that oligosaccharides containing α and β linkages within the same molecule can be constructed in one pot via a preactivation based approach with higher glyco-assembly efficien...

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Multi-component one-pot synthesis of the tumor-associated carbohydrate antigen Globo-H based on preactivation of thioglycosyl donors.

The assembly of an oligosaccharide library has been achieved in a practical and efficient manner employing a' one-pot sequential approach. With the help of the anomeric reactivity values of thioglycosides, using a thioglycoside (mono- or disaccharide) with one free hydroxyl group as acceptor and donor coupled with another fully protected thioglycoside, a di- or trisaccharide is selectively formed without self-condensation and subsequently reacted in situ with an anomerically inactive glycoside (mono- or disaccharide) to form a tri- or tetrasaccharide in high overall yield. The approach enables the rapid assembly of 33 linear or branched fully protected oligosaccharides using designed building blocks. These fully protected oligosaccharides have been partially or completely deprotected to create 29 more structures to further increase the diversity of the library.

Xin-Shan Ye

Papers

Programmable one-pot oligosaccharide synthesis

Iterative One‐Pot Synthesis of Oligosaccharides

Programmable One‐Pot Oligosaccharide Synthesis.

Multi-component one-pot synthesis of the tumor-associated carbohydrate antigen Globo-H based on preactivation of thioglycosyl donors.

Anomeric reactivity-based one-pot oligosaccharide synthesis: a rapid route to oligosaccharide libraries.