Highly diastereoselective entry into chiral spirooxindole-based 4-methyleneazetidines via formal [2+2] annulation reaction

We describe here a diastereoselective, DABCO-catalyzed reaction of allenoates with chiral N-tert-butanesulfinyl ketimines derived from isatin

Chlorine Dioxide Degradation Issues on Metal and Plastic Water Pipes Tested in Parallel in a Semi-Closed System

Chlorine dioxide (ClO2) has been widely used as a disinfectant in drinking water in the past but its effects on water pipes have not been investigated deeply, mainly due to the difficult experimental set-up required to simulate real-life water pipe conditions. In the present paper, four different kinds of water pipes, two based on plastics, namely random polypropylene (PPR) and polyethylene of raised temperature (PERT/aluminum multilayer), and two made of metals, i.e., copper and galvanized steel, were put in a semi-closed system where ClO2 was dosed continuously. The semi-closed system allowed for the simulation of real ClO2 concentrations in common water distribution systems and to simulate the presence of pipes made with different materials from the source of water to the tap. Results show that ClO2 has a deep effect on all the materials tested (plastics and metals) and that severe damage occurs due to its strong oxidizing power in terms of surface chemical modification of metals and progressive cracking of plastics. These phenomena could in turn become an issue for the health and safety of drinking water due to progressive leakage of degraded products in the water

The spiropiperidine-3,3 '-oxindole scaffold : a type II beta-turn peptide isostere

An unprecedented chiral spiropiperidine oxindole system quaternary 3-aminooxindole and relying on a ring closing acts as an highly constrained Freidinger gamma-lactam, adopting assessed by modelling and spectroscopical studies. was synthesized starting from enantiopure metathesis as the key step. This compound a type II beta-turn conformation in solution, as (C) 2010 Elsevier Ltd. All rights reserved

Organocatalytic access to enantioenriched spirooxindole-based 4-methyleneazetidines

This work describes the synthesis of enantioenriched spiro compounds, incorporating the azetidine and the oxindole motifs. The preparation relies on a formal [2 + 2] annulation reaction of isatin-derived N-tert-butylsulfonyl ketimines with allenoates. The asymmetric induction is secured by an organocatalytic strategy, exploiting a bifunctional cinchona-type \uce\ub2-isocupridine-based catalyst. Some post-transformation products, including unexpected spiropyrroline and 3,3-disubstituted oxindole derivatives, are also presented

Asymmetric Ugi 3CR on isatin-derived ketimine: Synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

An efficient Ugi three-component reaction of a preformed chiral ketimine derived from isatin with various isonitrile and acid components has been developed. The reactions proceeded smoothly and in a stereocontrolled manner with regard to the new center of the Ugi products due to the stereoinduction of the amine chiral residue. A wide variety of novel chiral 3,3-disubstituted 3-aminooxindoles were obtained, a selection of which were subjected to post-Ugi transformations, paving the way to application as peptidomimetics

One-Pot Synthesis of Sustainable High-Performance Thermoset by Exploiting Eugenol Functionalized 1,3-Dioxolan-4-one

1,3-Dioxolan-4-one (DOX) chemistry was explored for production of "one-pot" biobased polyester thermosets. DOX monomer was first functionalized by naturally occurring eugenol to introduce a structural element, which could induce cross-linking reaction through cationic polymerization of the double bond. The feasibility of polymerizing DOX monomers bearing bulky side groups was proven by model phenol-substituted DOX monomer (PhDOX). Once the reaction was shown to be effective, the same protocol was applied to eugenol-substituted monomer (EuDOX). A brief screening of the optimal catalyst concentration was performed, to obtain a highly cross-linked product. The synthesized thermoset showed good thermal resistance and high mechanical strength probably due to the rich aromatic content. The obtained thermoset was further subjected to microwave-assisted hydrothermal degradation test, which demonstrated complete recyclability to water or methanol soluble products. NMR and matrix-assisted laser desorption/ionization-mass spectroscopy analyses of the obtained degradation products unveiled the structure of the thermoset, strongly indicating that the polymerization of eugenol-functionalized DOX monomer resulted in polylactide-like chains connected with aromatic-aliphatic segments resulting from the reaction of the eugenol double bonds. The presence of free hydroxyl and carboxyl groups sheds light on the mechanism behind the observed shape-memory and self-healing properties

Polylactide/cellulose nanocrystals : The in situ polymerization approach to improved nanocomposites

The in situ polymerization of L-lactide in the presence of various amounts of cellulose nanocrystals (CNC) is described. CNC was prepared efficiently by acidic hydrolysis of cotton linters. Molecular weight, morphology, thermal, mechanical and crystallization properties of the PLA-CNC nanocomposites were evaluated. From size-exclusion chromatography (SEC) analysis, the actual occurrence of chemical bond between CNC and PLA can be assessed. The effect of CNC has been evaluated through differential scanning calorimetry (DSC) analysis, which highlights the probable formation of \uce\ub1\ue2\u80\ub2 crystals in the obtained materials. More importantly, from thermogravimetric analysis (TGA) a marked improvement in thermal stability of nanocomposites has been demonstrated, with respect to standard PLA and to previously described PLA-CNC blends. Nanocomposites show also an improvement in rheological properties with respect to standard PLA. In particular, storage modulus greatly increases, indicating a reinforcing effect of CNC. The described in situ synthetic methodology allows an optimal compatibilization between the two entities (PLA and CNC), facing one of the major problems inherent to the preparation of nanocomposites. It leads furthermore to remarkably improved thermal and rheological properties of the obtained materials

Role of Prolactin Receptors in Lymphangioleiomyomatosis

Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations in the tumor suppressor genes encoding Tuberous Sclerosis Complex (TSC) 1 and TSC2. The protein product of the TSC2 gene is a well-known suppressor of the mTOR pathway. Emerging evidence suggests that the pituitary hormone prolactin (Prl) has both endocrine and paracrine modes of action. Here, we have investigated components of the Prl system in models for LAM. In a TSC2 (+/-) mouse sarcoma cell line, down-regulation of TSC2 using siRNA resulted in increased levels of the Prl receptor. In human LAM cells, the Prl receptor is detectable by immunohistochemistry, and the expression of Prl in these cells stimulates STAT3 and Erk phosphorylation, as well as proliferation. A high affinity Prl receptor antagonist consisting of Prl with four amino acid substitutions reduced phosphorylation of STAT3 and Erk. Antagonist treatment further reduced the proliferative and invasive properties of LAM cells. In histological sections from LAM patients, Prl receptor immuno reactivity was observed. We conclude that the Prl receptor is expressed in LAM, and that loss of TSC2 increases Prl receptor levels. It is proposed that Prl exerts growth-stimulatory effects on LAM cells, and that antagonizing the Prl receptor can block such effects

Cellulose nanofibrils as reinforcing agents for PLA-based nanocomposites: T An in situ approach

One-pot in situ polymerization approach was explored for the preparation of polylactide (PLA)-cellulose nano- fibril (CNF) bio-nanocomposites. CNF were first prepared through enzymatic and mechanical treatment of bleached hardwood kraft pulp. The bio-nanocomposites- were then fabricated through ring opening poly- merization (ROP) of L-lactide, in the presence of various amounts of fibrils. Molecular weight, thermal prop- erties, surface morphology, mechanical and wettability properties of the PLA-CNF nanocomposites were eval- uated. DSC analysis demonstrated the effect of CNF on crystallization and crystalline morphology of PLA. Improved modulus for the nanocomposites with respect to standard PLA was demonstrated, however, the dif- ferences in tensile stress were small probably due to the counteracting effects of reinforcement from CNF and the decreasing molecular weight as a function of CNF concentration. The absence of pulled-out fibers was assessed, highlighting the strong interface and covalent attachment of PLA chains on CNF surface. Finally, the covalent bonding of PLA chains on CNF surface was demonstrated by isolating the non-soluble part, consisting of PLA- grafted CNF, and characterization of this residue

Urogenital Abnormalities in Adenosine Deaminase Deficiency

BACKGROUND: Improved survival in ADA-SCID patients is revealing new aspects of the systemic disorder. Although increasing numbers of reports describe the systemic manifestations of adenosine deaminase deficiency, currently there are no studies in the literature evaluating genital development and pubertal progress in these patients. METHODS: We collected retrospective data on urogenital system and pubertal development of 86 ADA-SCID patients followed in the period 2000-2017 at the Great Ormond Street Hospital (UK) and 5 centers in Italy. In particular, we recorded clinical history and visits, and routine blood tests and ultrasound scans were performed as part of patients' follow-up. RESULTS AND DISCUSSION: We found a higher frequency of congenital and acquired undescended testes compared with healthy children (congenital, 22% in our sample, 0.5-4% described in healthy children; acquired, 16% in our sample, 1-3% in healthy children), mostly requiring orchidopexy. No urogenital abnormalities were noted in females. Spontaneous pubertal development occurred in the majority of female and male patients with a few cases of precocious or delayed puberty; no patient presented high FSH values. Neither ADA-SCID nor treatment performed (PEG-ADA, BMT, or GT) affected pubertal development or gonadic function. CONCLUSION: In summary, this report describes a high prevalence of cryptorchidism in a cohort of male ADA-SCID patients which could represent an additional systemic manifestation of ADA-SCID. Considering the impact urogenital and pubertal abnormalities can have on patients' quality of life, we feel it is essential to include urogenital evaluation in ADA-SCID patients to detect any abnormalities, initiate early treatment, and prevent long-term complications