2-O-Acetyl-3,4,5,6-tetra-O-benzyl-D-myo-inosityl diphenylphosphate: a new useful intermediate to inositol phosphate and phospholipids

Inositol phosphates and inositol phospholipids are ubiquitous in biochemistry and play a central role in cell signaling and regulation events. For this reason, their synthesis has attracted widespread interest. This paper describes the preparation of a new optically active inositol phosphate derivative, 2-O-acetyl-3,4,5,6-tetra-O-benzyl-D-myo-inosityl diphenylphosphate (6), and its characterization by spectroscopic methods. Compound (6) represents a useful intermediate for the preparation of inositol phosphate and phospholipids, in particular of glycerophosphoinositol (GPI), a natural anti-inflammatory agent

Immobilization of old yellow enzymes via covalent or coordination bonds

Ene-reductases (ERs) belonging to the old yellow enzyme (OYE) family have been thoroughly investigated for the stereospecific reduction of activated prochiral C=C double bonds. In this work, OYE3 was immobilized both by covalent binding on glyoxyl-agarose (OYE3-GA), and by affinity-based adsorption on EziG™ particles (OYE3-EziG). The immobilized OYE3-GA was demonstrated to be active (activity recovery = 52%) and to retain almost 100% of its activity under the enzymatic assay conditions (50 mM phosphate buffer pH 7, 28 °C) for six days, whereas the activity of the non-immobilized enzyme dropped to 50% after two days. In the case of EziG™, the highest activity recovery (54%) was achieved by using the most hydrophilic carrier (EziG™ Opal) that was selected for the full characterization of this type of enzyme preparation (stability, recycling, re-use, enzyme leakage). OYE3-EziG was slightly less stable than OYE3-GA under the same experimental conditions. OYE3-GA could be recycled and re-used for up to 12 reaction cycles in the bioreduction of α-methyl-trans-cinnamaldehyde; after 12 runs, the highest conversion achieved was 40%. In the case of the co-immobilized OYE3/GDH-EziG, the conversion dropped to 56% after two reaction cycles. No enzyme leakage was detected over 48 h for both OYE3-GA and OYE3/GDH-EziG (50 mM phosphate buffer pH 7, 28 °C). These seed results pave the way for a true optimization of the immobilization of OYE3, as well as for the use of immobilized OYE3 for preparative applications both in batch and continuous flow conditions

Synthesis of Ribavirin, Tecadenoson, and Cladribine by enzymatic transglycosylation

Despite the impressive progress in nucleoside chemistry to date, the synthesis of nucleoside analogues is still a challenge. Chemoenzymatic synthesis has been proven to overcome most of the constraints of conventional nucleoside chemistry. A purine nucleoside phosphorylase from Aeromonas hydrophila (AhPNP) has been used herein to catalyze the synthesis of Ribavirin, Tecadenoson, and Cladribine, by a “one-pot, one-enzyme” transglycosylation, which is the transfer of the carbohydrate moiety from a nucleoside donor to a heterocyclic base. As the sugar donor, 7-methylguanosine iodide and its 2′-deoxy counterpart were synthesized and incubated either with the “purine-like” base or the modified purine of the three selected APIs. Good conversions (49-67%) were achieved in all cases under screening conditions. Following this synthetic scheme, 7-methylguanine arabinoside iodide was also prepared with the purpose to synthesize the antiviral Vidarabine by a novel approach. However, in this case, neither the phosphorolysis of the sugar donor, nor the transglycosylation reaction were observed. This study was enlarged to two other ribonucleosides structurally related to Ribavirin and Tecadenoson, namely, Acadesine, or AICAR, and 2-chloro-N6-cyclopentyladenosine, or CCPA. Only the formation of CCPA was observed (52%). This study paves the way for the development of a new synthesis of the target APIs at a preparative scale. Furthermore, the screening herein reported contributes to the collection of new data about the specific substrate requirements of AhPNP

Emulsifying properties of sugar-based surfactants prepared by chemoenzymatic synthesis

Sugar Fatty Acid Esters (SFAEs) are a class of non-ionic surfactants that can be synthesized from inexpensive natural resources. Depending on carbon chain length and nature of the sugar head group, SFAEs cover a wide range of hydrophilic–lipophilic balance (HLB) values, which result in tunable tenside properties and in turn relevant for a wide variety of industrial applications. Three sugar-based surfactants (6-O-lauroyl-, 6-O-palmitoyl- and 6-O-stearoyl-1-O-butyl glucopyranosides) have been prepared by a lipase-catalyzed esterification of isomeric mixture of n-butyl glucosides. Specifically, their interfacial features together with W/O emulsifying properties and stability over time have been finely evaluated (interfacial tension (IFT) values, W/O emulsion turbidity water droplet size distribution, first order kinetic constants of de-emulsification)

Deep Eutectic Solvents for the Enzymatic Synthesis of Sugar Esters: A Generalizable Strategy?

Sugar (fatty acid) esters are industrially relevant compounds, with a cumbersome production process due to the solubility issues of the substrates, which forces the use of environmentally unfriendly reaction media. Herein, deep eutectic solvents (DESs) are considered as a promising solution: several literature examples use glucose and different acyl donors to illustrate the efficient synthesis of sugar esters in classic DESs like choline chloride/urea (ChCl/U). However, this paper discloses that when sugars like lactose or other disaccharides are used, enzymes cannot efficiently perform (trans)esterifications in DESs, while the same reaction can proceed in mixtures like pyridine/tetrahydrofuran (Py/THF). This could be explained by computational solubility studies and molecular dynamics simulations of both reaction media, showing two effects: (i) on the one hand, large acyl donors (more than C10) display poor solubility in DESs and (ii) on the other hand, disaccharides interact with DES components. Thus, the DES affects the conformation of lactose (compared to the conformation observed in the Py/THF mixture), in such a way that the enzymatic reaction results impaired. Despite that classic DESs (e.g., ChCl/U) may not be useful for generalizing their use in saccharide ester syntheses, the achieved theoretical understanding of the reaction may enable the design of future DESs that can combine enzyme compatibility with eco-friendliness and efficiency in sugar chemistry

Synthesis of ribavirin, tecadenoson, and cladribine by enzymatic transglycosylation

Despite the impressive progress in nucleoside chem. to date, the synthesis of nucleoside analogs is still a challenge. Chemoenzymic synthesis has been proven to overcome most of the constraints of conventional nucleoside chem. A purine nucleoside phosphorylase from Aeromonas hydrophila (AhPNP) has been used herein to catalyze the synthesis of Ribavirin, Tecadenoson, and Cladribine, by a "one-pot, one-enzyme" transglycosylation, which is the transfer of the carbohydrate moiety from a nucleoside donor to a heterocyclic base. As the sugar donor, 7-methylguanosine iodide and its 2'-deoxy counterpart were synthesized and incubated either with the "purine-like" base or the modified purine of the three selected APIs. Good conversions (49-67%) were achieved in all cases under screening conditions. Following this synthetic scheme, 7-methylguanine arabinoside iodide was also prepd. with the purpose to synthesize the antiviral Vidarabine by a novel approach. However, in this case, neither the phosphorolysis of the sugar donor, nor the transglycosylation reaction were obsd. This study was enlarged to two other ribonucleosides structurally related to Ribavirin and Tecadenoson, namely, Acadesine, or AICAR, and 2-chloro-N6-cyclopentyladenosine, or CCPA. Only the formation of CCPA was obsd. (52%). This study paves the way for the development of a new synthesis of the target APIs at a preparative scale. Furthermore, the screening herein reported contributes to the collection of new data about the specific substrate requirements of AhPNP. [on SciFinder(R)

The shape of things to come?: household dependency ratio and adolescent nutritional status in rural and urban Ethiopia

Several related demographic trends are occurring in developing countries: youth comprise a large portion of populations, fertility rates are declining, and urban dwellers are increasing. As fertility rates decline and populations age, the decline in the ratio of young dependents to working age adults is expected to free up household resources, which can be invested in human capital, including youth nutritional wellbeing. We test this hypothesis in a sample of youth (n = 1,934) in Southwestern Ethiopia. Multiple measures of achieved growth and nutritional status are explored (weight, height, mid-upper arm circumference (MUAC), body mass index (BMI) and body mass index for age z-score (BMIZ), weight for age z-score (WAZ), and height for age z-score (HAZ)). In multivariable models controlling for the effects of income, age, gender, and youth is workloads, youth living in rural settings had significantly lower weight (1.24 kg lighter), MUAC (0.67 cm lower), BMI (0.45 BMI lower), BMIZ (0.27 lower), HAZ (0.14 HAZ lower), and WAZ (0.3 WAZ lower) than urban youth (all P < 0.01). Compared with youth in the lowest dependency ratio households, results show that youth in households with the highest dependency ratios were estimated to be 1.3 kg lighter, have 0.67 cm smaller MUAC, and BMI that was 0.59 lower (all P<0.01). Similar results were found for WAZ (0.21 lower) and BMIZ (0.36 lower). Youth height and HAZ were not associated with household dependency. These results may point toward increasing levels of human capital investments in Ethiopian youth as fertility levels decline and populations urbanize. Am J Phys Anthropol 144:643–652, 2011

Il "Patto dei Sindaci" promosso dall'U.E. Analisi delle strategie di una Governance Multilivello

La tesi tratta principalmente l'iniziativa intrapresa dall'Unione Europea in materia di energia sostenibile, tramite l'accordo denominato "Patto dei Sindaci". Tale accordo mira al miglioramento della gestione territoriale attraverso una governance multilivello che parte dal basso (piccole entità locali come i comuni) al fine di raggiungere degli obiettivi comuni di diminuzione delle emissioni di CO2 entro il 2020. Per raggiungere questi risultati il Patto dei Sindaci si avvale di uno strumento fondamentale per la pianificazione e per gli interventi da effettuare, che prende il nome di Piano d'Azione per l'Energia Sostenibile PAES. Ogni singolo Firmatario del Patto sarà tenuto a redigere un proprio Piano d'Azione in funzione delle proprie caratteristiche, delle singole esigente e dei propri obiettivi. A delineare tale Piano d'Azione il Firmatario potrà avvalersi di Coordinatori, Sostenitori, Partner Associati e Agenzie per l'Energia presenti anche loro all'interno del patto. Tutto questo per garantire una maggiore efficienza al raggiungimento di obiettivi prefissati. In particolare si andrà ad analizzare il caso studio del PAES del Comune di San Mauro Pascoli

Biocatalysis for the sustainable production of bio-based ingredients from renewable resources

L’obiettivo di questa ricerca è l’ottenimento di prodotti ad alto valore aggiunto da fonte rinnovabile mediante un approccio chimico, enzimatico, o chemoenzimatico. Nella prima parte della Tesi, il glicerofosfoinositolo (GPI) e la glicerofosfocolina (GPC), aventi rispettivamente proprietà antinfiammatorie e di cognitive enhancer, sono stati ottenuti dalla lecitina di girasole, un sottoprodotto dell'estrazione e della raffinazione dell’olio, mediante idrolisi enzimatica con lipasi e/o fosfolipasi. Nella seconda parte della Tesi, è stata intrapresa la sintesi di sugar fatty acid esters (SFAE), emulsionanti non ionici, utilizzando il lattosio e i suoi prodotti di idrolisi (glucosio e galattosio) come materia prima. Il lattosio è il componente più abbondante del siero di latte, il principale sottoprodotto dell'industria lattiero-casearia, che può quindi essere valorizzato come biomassa, nonchè come fonte di carbonio per la produzione, mediante fermentazione, di acidi grassi/gliceridi utilizzati per la sintesi di SFAE. Per lo studio delle reazioni di esterificazione/transesterificazione enzimatica/chemoenzimatica degli zuccheri con acidi grassi/esteri, rispettivamente, sono state applicate diverse strategie: derivatizzazione dello zucchero, uso di solventi non convenzionali (DES) e organocatalisi.This research aims at obtaining high-added value chemicals from renewable resources by using either a chemical or an enzymatic approach, as well as a combination of both. On one hand, glycerophosphoinositol (GPI) and glycerophosphocholine (GPC) which have anti-inflammatory and cognitive enhancer properties, respectively, were obtained from sunflower lecithin, a by-product of oil extraction and refining, by (phospho)lipase-catalyzed hydrolysis of pre-treated lecithin. On the other hand, sugar fatty acid esters (SFAE), which are non-ionic emulsifiers, were synthesized by using lactose as well as its hydrolysis products (glucose and galactose) as raw materials. Lactose is the most abundant component of cheese whey, the main waste stream of dairy industry, that can be upgraded, indeed, as a pool of sugars and as a carbon source for microbial production of fatty acids/glycerides which constitute the “hydrophobic tail” of SFAE. A fine-tuning of the enzymatic/chemoenzymatic esterification/transesterification of the sugars with fatty acids/esters, respectively, was needed to overcome the opposite solubility profiles of the sugar “polar head” and the fatty acid “tail”. Derivatization of the sugar, investigation of non-conventional media (DES), and organocatalysis were explored to this aim