COVID-19 and pneumonia: a role for the uPA/uPAR system

Here, we highlight recent findings on the urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system that suggest its potential role as a main orchestrator of fatal progression to pulmonary, kidney, and heart failure in patients with coronavirus. Patients with prolonged background inflammation can present aberrant inflammatory reactions, well recognized as the main factors that can result in death and probably sustained by a dysregulated uPA/uPAR system. SuPAR, the soluble form of uPAR, represents a biomarker of disease progression, and its levels correlate well with comorbidities associated with the death of patients with coronavirus. New drugs that regulate the uPA/uPAR system could help treat the severe complications of highly pathogenic human coronaviruses (hCoVs), including pandemic coronavirus 2019 (COVID-19)

Site-selective indole oxidation catalyzed by a Mn-containing artificial metalloenzyme

Metalloenzymes have become attractive tools for application in oxidation catalysis, since a complex protein environment exerts a highly specific control on the reactivity of the metal center.1 Compared to synthetic catalysts, enzymes cover only a limited repertoire of reactions and substrates. The development of hybrid catalysts, obtained by anchoring catalytic metal complexes to native or artificial biomolecular scaffolds, is aimed at merging the advantages of both systems while overcoming the drawbacks.2,3 In this area, our research is devoted to the development of peptide-porphyrin conjugates resembling natural heme-proteins, called “Mimochromes”.3,4 Among them, Mimochrome VIa (MC6a) is the most promising catalyst, thanks to its robust but flexible scaffold. MC6a, in its MnIII complex, (Mn-MC6a) is an efficient catalyst with enzyme-like properties, because fast and chemoselective reactions with a peroxygenase-like mechanism were found in the oxidation of thioethers. Even more remarkably, Mn-MC6a selectively exhibits either peroxygenase- or catalase-like activity depending on the reaction conditions. Here we present the oxidation of indole and its derivatives catalyzed by Mn-MC6a, with the aim of exploiting the catalytic properties of this artificial enzyme in reactions with potential synthetic applications. Indole is one of the most common heterocyclic scaffolds available in nature. It occurs in several natural compounds (such as alkaloids and plant hormones) and is part of many pharmaceuticals.5-8 Despite the structural simplicity of this molecule, indole oxidation leads to a large number of products, including mono- and di-oxygenated compounds. Indole oxidation has been studied with both biological5,6 and synthetic7,8 catalysts. In all the approaches described so far, no or weak selectivity toward any of the oxidation products has been reported.5-8 Conversely, Mn-MC6a is able to oxidize indole under unprecedented site-selective conditions, yielding to 3-oxindolenine as single product. Additionally, the reaction selectivity is dramatically altered when 1- or 3-methyl-substituted indoles are used as substrates. A detailed mechanistic analysis will help to rationalize the outstanding selectivity of the catalyst. References: 1. Sheldon, R. A. and Woodley, J. M. Chem. Rev. 2018, 118, 801–838. 2. Schwizer, F. et al. Chem. Rev. 2018, 118, 142-231. 3. Chino, M. et al. Biopolymers 2018 (doi: 10.1002/bip.23107). 4. Nastri, F. et al. Chem. Soc. Rev., 2016, 45, 5020-5054. 5. Kuo, H. H. and Mauk, A. G.; Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 13966–13971. 6. Barrios, D. A. et al. J. Am. Chem. Soc. 2014, 136, 7914-7925. 7. Linhares, M. et al. Appl. Catal. A. 2014, 470, 427–433. 8. Poon L. C.-H. et al. J. Am. Chem. Soc. 2011, 133, 1877–1884

STEREOSELECTIVE METHODS IN THE SYNTHESIS OF BIOACTIVE OXATHIOLANE AND DIOXOLANE NUCLEOSIDES

Chemical Synthesis of Nucleoside Analogues examines the application of synthetic methodologies to the preparation of compounds of biological interest, including the synthesis of nucleic acids on pre-existing nucleic acid templates, assembling RNA, or DNA. This comprehensive compendium culls expert contributions that highlight the structural components of nucleosides (supported by spectral data) and their modification as well as the synthetic strategies based on chemical approaches. The text serves undergraduate students, specialists, and researchers, allowing access to a variety of compounds without forgetting the biological importance of the target compounds

Challenges in carbohydrate chemistry: a survey of modern approaches for L-hexose stereoselective synthesis in Stereochemistry research trends

Stereochemistry is an important facet of chemistry. The study of stereochemical problems spans the entire range of organic, inorganic, biological, physical and supramolecular chemistries. Stereochemistry includes methods for determining and describing these relationships; the effect on the physical or biological properties these relationships impart upon the molecules in question, and the manner in which these relationships influence the reactivity of the molecules in question (dynamic stereochemistry). This book provides new research from around the globe on this field

Challenges in carbohydrate chemistry: a survey of modern approaches for L-hexose stereoselective synthesis

Stereochemistry is an important facet of chemistry. The study of stereochemical problems spans the entire range of organic, inorganic, biological, physical and supramolecular chemistries. Stereochemistry includes methods for determining and describing these relationships; the effect on the physical or biological properties these relationships impart upon the molecules in question, and the manner in which these relationships influence the reactivity of the molecules in question (dynamic stereochemistry). This book provides new research from around the globe on this field

Recent Advances in Monosaccharide Synthesis: A Journey into L-Hexose World

Last years have witnessed enormous progresses in glycomic field, mainly as a consequence of the crucial role carbohydrates have shown in biological systems. While up to a few years ago attention was mainly focused on the use of easily available D-sugars, a recent interest has emerged around their L-enantiomers, as they have been found to be key components of several bioactive compounds, whether in the form of oligosaccharides, glycopeptides, terpene glycosides or other clinically useful agents. However, L-sugars (L-hexoses especially) are rather rare in nature and not easily accessi-ble from inexpensive sources. As demand for their synthesis in considerable amount and high purity is more and more pressing, intense efforts have been addressed to the development of new and general methodologies for their construction. This review covers the synthetic routes to L-hexoses, mainly those coming from the new century. Methodologies for monosaccharide assembly will comprise de novo approaches, based on carbon chain elongation, hetero Diels-Alder reaction, asymmetric dihydroxylation up to the most recent amino acid-catalyzed aldol addition – as well as D-sugar manipulation strategies, including epimerization by chemical or enzymatic methods. Application of such protocols for the construction of biologically relevant oligosaccharides and natural products will be also briefly mentioned

Access to unnatural oligosaccharides under mild glycosidation conditions

Herein, we report a new strategy for the synthesis of oligosaccharides containing enantiopure L-hexoses. Key for the success of this approach is the use of alfa-L- and beta-L-sugar derivatives, whose preparation through a “domino” reaction starting from the dithiin containing system has already been at the core of previous studies on the synthesis of the whole series of L-hexoses

Rapid access to 1,6-anhydro-beta-L-hexopyranose derivatives via domino reaction: synthesis of L-allose and L-glucose

An expeditious and efficient synthesis of 1,6-anhydro--Lhexopyranosyl derivatives 3 as valuable building blocks for the preparation of L-sugars is herein reported. This route relies upon the use of a domino reaction involving five synthetic steps from the 5,6-dihydro-1,4-dithiin 4. As 1,6- anhydro derivatives 3 are obtained, dithioethylene bridge removal and double-bond dihydroxylation give access to protected L-allose and L-glucose in stereoselective fashion and high yields

Sulfur-assisted domino access to bicyclic dihydrofurans: case study and early synthetic applications

A DDQ-mediated domino reaction (up to six steps in a single process) has been developed to selectively provide substituted dihydrofurans from a common starting material containing a cyclic bis-thioenol ether. Study of the reaction mechanism highlighted a role played by the sulfur-containing moiety in influencing reaction rate and stereoselectivity