Stereoselective Synthesis of Selenium-Containing Glycoconjugates via the Mitsunobu Reaction

A simple and efficient route for the synthesis of new glycoconjugates has been developed.The approach acts as a model for a mini-library of compounds with a deoxy-selenosugar core joinedto a polyphenolic moiety with well-known antioxidant properties. An unexpected stereocontroldetected in the Mitsunobu key reaction led to the most attractive product showing a natural Dconfiguration. Thus, we were able to obtain the target molecules from the commercially availableD-ribose via a shorter and convenient sequence of reaction

Microwave Assisted Synthesis of Pyridophenoxazinones, a Class of Powerful Antiproliferative Compounds

In order to obtain new antiproliferative compounds good for acting through the forementioned mechanisms, including DNA intercalation and topoisomerase inhibition, our attention was focused on the derivatives of pyridophenoxazinone (PPH, 1 R=H) system, an iminoquinone containing a planar tetracyclic system suitable for intercalating DNA G-C base pairs in a site specific mode(2). Namely, we designed, after molecular modeling calculations, PPH carboxyamide derivatives holding at C-9 and C-10 positions an amino acidic chain or a sugar. Unfortunately, the real obstacle to the availability of such molecule was represented by their synthesis. Therefore, in our opinion it seems to be worthwhile to report a new microwave (μW) assisted synthetic procedure to prepare PPH carboxyamides. In order to assess the validity of our method, we applied the procedure to the synthesis of variously substituted PPHs 1 and received evidence that microwave irradiation enables the preparation of those compounds in high yields and short reaction times

Fullerene-derivates containing selenium

Over the years, fullerenes have been covalently linked to other polar structures, increasing its aqueous solubility, thereby improving its potential use for biological and biomedical applications.1 The functionalization of C60, the most study fullerene, with biomolecules shows one of the best approaches to increase their bioavailability and access the benefits of these molecules.2 C60 derivatives have shown antioxidants and antivirals propierties. In adition, remarkable examples relate with the synthesis of C60 hybrids, where the [60]fullerene is covalently connected to biological active compounds such as sugars and steroids have affinity to some nucleic acids, proteins and cellular receptors.3 In the frame of a consolidated research focused on the versatility of steroid-C60 hybrids,4 we propose the synthesis of new methanofullerenes 1 (Scheme 1) containing selenium with potential antiviral and antioxidant propierties by a synergistic activity of selenium and the C60. The new methano[60]fullerenes were prepared using a cyclopropanation reaction employed the Bingel–Hirsch protocol in a multistep synthetic procedure. The precursors malonates contained three sterols – diosgenine, cholesterol, and stradiol – and a D-selenodeoxysugar 3. These conjugates were synthetized in good yields based on the consolidated synthetic technique performed previously by our reserch group5 and a computational study was carried out. Theoretical calculations using the DFT-PBE method and 6-311G(d,p) basis set, were performed to predict the most stable conformations for the synthesized conjugates (2). For the more, the applications of the novel steroid-selenosugar conjugates were also evaluated in medicinal chemistry, in particular, was explored their potential application as anti-SarsCov-2 agents. The molecular docking suggested that the conjugates form H-bonds with the active residues involved in the interaction of RBD-SarsCov-2 with ACE-2. How RBD protein plays an important role in the entry of virus in the cellule, the conjugates could be considerate with potential antivirals propierties

New Seleno-Glyconjugates for Nutraceutical Application

Oxidative stress is a disequilibrium redox condition that occurs due to high concentration of prooxidant reactive species (RS) and, by comparison, a lower concentration of endogenous antioxidants in the body.1 Oxidative stress, caused by RS, is involved into the genesis of different pathologies such as inflammatory bowel disease, cardiovascular disease, Alzheimer’s disease, diabetes and cancer.2 Nutraceuticals could be used to prevent oxidative stress as an additional health benefit along with nutrition.1 The use of exogenous antioxidants can ameliorate this stressful condition and restore the redox disequilibrium.3 Polyphenols have a potential health-promoting effect, however, show a low bioavailability.4 For this reason, synthesis of organic seleniumcompounds combined to (poly)phenolic compounds could increase the solubility and exert their potential synergistic antioxidant effects. The approach proposed consists of preparing the D-ribose derivative 1 to obtain the donor 2 then employed to produce glycoconjugates containing well known (poly)phenols through a Mitsunobu reaction.5 To assess the bioactivity of selenoglycoconjugates, DPPH and ABTS antiradical assays were performed, while the effects on cell proliferation were preliminarily investigated on SH-SY5Y cells. The phenol moiety greatly affected both the antiradical efficacy and the mitochondrial redox activity. The glycoconjugates, especially at the highest tested concentrations, exhibited cytotoxic effects lower than that of unconjugated phenolic compounds, underlining the mitigating impact of selenosugar

N-4 Alkyl Cytosine Derivatives Synthesis: A New Approach

The selective N-4 alkylation of cytosine plays a critical role in the synthesis of biologically active molecules. This work focuses on the development of practical reaction conditions toward a regioselective synthesis of N-4-alkyl cytosine derivatives. The sequence includes a direct and selective sulfonylation at the N-1 site of the cytosine, followed by the alkylation of the amino siteusing KHMDS in CH2Cl2/THF mixture, providing a fast and efficient approach consistent withpyrimidine-based drug design

An 1H NMR study of the cytarabine degradation in clinical conditions to avoid drug waste, decrease therapy costs and improve patient compliance in acute leukemia

Cytarabine, the 4-amino-1-(β-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C) is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers' instructions, once the components-sterile water and cytarabine powder-are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4°C. To evaluate how to avoid wasting the drug in short-term, low-dose treatment regimens, the reconstituted samples, stored at 25°C and 4°C, were analyzed every day of the test week by reversed-phase HPLC and high-field NMR spectroscopy. All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4°C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. Our findings show that an cytarabine solution prepared and stored in the original vials retains its efficacy and safety and can, therefore, be divided into small doses to be administered over more days, thus avoiding unnecessary expensive and harmful waste of the drug preparation. Moreover, patients who require daily administration of the drug could undergo the infusion at home without need to go to hospital. The stability of the aliquots would help decrease hospitalization costs

56. Towards New Exogenous Antioxidant Supplements organo-Se-based.

Even though oxidative stress (OS), a disequilibrium redox state, is a major risk factors for the development of several medical illnesses, such as cardiovascular disease, age-related neurodegenerative diseases, and several types of cancer, epidemiological studies have shown that eating foods high in antioxidants or using exogenous antioxidant supplementation may help to lower this risk. 1 Nutraceuticals are of particular interest; indeed, they might be used to prevent or mitigate OS by providing other health advantages in addition to nutrition.2 Within this frame of reference, our research is focused on Selenium (Se) and polyphenols. The former is one of the trace elements involved in immunological system, growth, healthy muscular activity, reproductive organs, decreases the toxicity of some elements such as mercury responses and whose deficiency is linked to immune, cardiac, muscular, bone, and other disease. 3 The latter are acknowledged to have health-promoting properties, although their limited bioavailability is frequently blamed. Within this framework of assessing their real potential as an approach to combating diseases, it is well known that glycosylation affects the chemical, biological, and physical characteristics of polyphenols, allowing for greater absorption in the small intestine. 4 Thus, the synthesis of organo-Se-compounds with a sugar-type structure, analogue to arbutin, coupled with (poly)phenols via Mitsunobu reactions aims to provide novel molecules that could overcome limited bioavailability while also providing a synergistic antioxidant effect. 5 DPPH and ABTS antiradical tests were used to evaluate the bioactivity of selenoglycoconjugates. Moreover, the effects on cell proliferation were preliminary investigated towards Caco-2 intestinal epithelial cells, SHSY5Y neuroblastoma cells, and HaCaT keratinocytes. The phenol moiety has a significant impact on both antiradical activity and mitochondrial redox activity. The cytotoxic effects of glycoconjugates, particularly at the highest tested doses, were lower than those of unconjugated phenolic compounds, highlighting the moderating influence of selenosugar

Diastereo- and Enantioselective Direct Aldol Reactions in Aqueous Medium: a New Highly Efficient Proline-Sugar Chimeric Catalyst.

Herein we reported that new proline derivatives synthesized in our laboratories actually the small molecules (1) and (2), catalyzed direct aldol reactions in water/brine leading to significant enatioselectivity and diasteroselectivity in the model reaction between cyclohexanone and benzaldehyd

Diastereo- and Enantioselective Direct Aldol Reactions in Aqueous Medium: a New Highly Efficient Proline-Sugar Chimeric Catalyst

Synthesis and successful applications in terms of chemical yields and diastereo-/enantiomeric ratios of a new catalyst in the DAA of cyclohexanone and acetone to variously substituted benzaldehydes have been presented

Studies toward Lipid A: synthetic strategy for enantioselective preparation of 3-hydroxy fatty acids

A short and efficient enantioselective synthesis of (R)-3-hydroxydodecanoic acid is described, involving a Sharpless asymmetric dihydroxylation to produce the required (R)-stereochemistry