Synthesis and Deriatization of Heterocyclic Systems under Sustainable Conditions.

In present days, the role of chemistry in every field of technology it is crucial. During the PhD period, with the aim to reduce the impact of chemical process, several protocols were developed in agreement with the principles of green chemistry. The use of enabling techniques has demonstrated to be of countless importance to achieve target products in higher yield and selectivity. Herein are reported some of the research carried out in this period

3-Alkylated indoles by reduction of sulfonyl indoles under flow chemical conditions

Reduction of 3-(1-arylsulfonylalkyl) indoles (sulfonyl indoles) using polymer-supported sodium borohydride under flow chemical conditions allows an efficient synthesis of 3-alkylindoles with a notable waste minimization and reduced solvent consumption. The flow conditions can be also applied to the synthesis of sulfonyl indoles which can be obtained by a three-component coupling of indoles with aldehydes and ptoluenesulfinic acid. Using the two-step flow chemical approach, 3-alkylindoles can be directly obtained from their remote indole and aldehyde precursors

β-Nitroacrylates: A Versatile and Growing Class of Functionalized Nitroalkenes

beta-Nitroacrylates are an important subclass of nitroolefins in which an ester and a nitro group are simultaneously linked, in alpha- and beta-positions, to a double bond. This peculiarity makes these nitro derivatives highly reactive with a plethora of nucleophiles, very often under extremely mild reaction conditions, and thus they can serve as excellent building blocks towards highly functionalized materials. Based on the growing application of beta-nitroacrylates in organic synthesis, we considered it to be useful to highlight in this review the most important results obtained over the last ten years

A new, low impact and efficient synthesis of ω-nitro esters under solid heterogeneous catalysis

Herein, we report a new, efficient and sustainable synthetic protocol for the preparation of omega-nitro esters starting from cyclic 2-nitro ketones. The method involves the use of polymer bound BEMP and provides the target compounds in excellent yields and low process mass intensity and E-factor values

A New Valuable Synthesis of Polyfunctionalized Furans Starting from β-Nitroenones and Active Methylene Compounds

Highly functionalized furans are the key scaffolds of many pharmaceuticals and bioactive natural products. Herein, we disclose a new fruitful synthesis of polyfunctionalized furans starting from beta-nitroenones and alpha-functionalized ketones. The protocol involves two steps promoted by solid supported species, and it provides the title targets from satisfactory to very good overall yields and in an excellent diastereomeric ratios

Synthesis of β-Nitro Ketones by Chemoselective Reduction of β-Nitro Enones under Solid Heterogeneous Catalysis

A new, simple and efficient chemoselective reduction of β-nitro enones to provide substituted β-nitro ketones, a strategic class of compounds, under solid heterogeneous palladium catalysis and in the presence of triethylsilane is presented. © Georg Thieme Verlag Stuttgart. New York

Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy

The therapeutic potential of a novel, targeted-release formulation of oral budesonide (Nefecon) for the treatment of IgA nephropathy (IgAN) was first demonstrated by the phase 2b NEFIGAN trial. To verify these findings, the phase 3 NefigArd trial tested the efficacy and safety of nine months of treatment with Nefecon (16 mg/d) versus placebo in adult patients with primary IgAN at risk of progressing to kidney failure (ClinicalTrials.gov: NCT03643965). NefIgArd was a multicenter, randomized, double-blind, placebo-controlled two-part trial. In Part A, 199 patients with IgAN were treated with Nefecon or placebo for nine months and observed for an additional three months. The primary endpoint for Part A was 24-hour urine protein-to-creatinine ratio (UPCR) after nine months. Secondary efficacy outcomes evaluated included estimated glomerular filtration rate (eGFR) at nine and 12 months and the UPCR at 12 months. At nine months, UPCR was 27% lower in the Nefecon group compared with placebo, along with a benefit in eGFR preservation corresponding to a 3.87 ml/min/1.73 m2 difference versus placebo (both significant). Nefecon was well-tolerated, and treatment-emergent adverse events were mostly mild to moderate in severity and reversible. Part B is ongoing and will be reported on later. Thus, NefIgArd is the first phase 3 IgA nephropathy trial to show clinically important improvements in UPCR and eGFR and confirms the findings from the phase 2b NEFIGAN study

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field