Vinylogous aldol reaction of heterocyclic silyloxy dienes. Application in synthesis

A versatile, readily accessible triad of 2-enoxy silane synthons derived from furan, pyrrole, and thiophene is presented. These heterocycles, in reacting with carbonyl and carbonyl- related acceptors, act as vinylogous nucleophile modules, giving rise to diverse, functionality- rich, γ-substituted α,β-unsaturated carbonyl constructs. These, in turn, are invaluable platforms onto which further functional elements and chirality may be introduced. A couple of appealing applications—the variable construction of a repertoire of carbasugars and a library of annonaceous acetogenin segments—have been chosen to illustrate the viability of this vinylogous aldol approach

Evaluation of effect of the primary particle size on compactibility of spray-dried lactoses

Spray-dried lactose is one of the most used filler-binders in direct compaction of tablets. Spray-dried lactose is produced by spray-drying a suspension of α-lactose monohydrate crystals in a saturated aqueous solution of lactoses. The resulting product is composed of spherical particles, containing 80-85% crystals of α-lactose monohydrate (primary particles) and 15-20% amorphous lactose The compactibility of two commercial spray-dried lactoses, Pharmatose® DCL 11 (DCL11), prepared from α-lactose monohydrate with a median primary particle size of 34 µm and a new product, Pharmatose® DCL 14 (DCL14), prepared from 20 µm primary particles, were investigated

Design and evaluation of dry-coated tablets for colonic delivery of diclofenac sodium

A colonic drug delivery system is required to protect a drug during its transit through the upper gastro-intestinal tract and allow its release in the colon. The aim of this study was the preparation of dry-coated tablets designed for colonic release of the model drug Diclofenac sodium (DS). The system consists of a drug-pectine (PC) mixture as the core and hydroxypropylmethylcellulose (HPMC) alone or mixed in different ratios with poly(ε-caprolactone) (CL) as the coat layer

Exploring the boundaries of vinylogous Mukaiyama aldol processes: stereoselective access to polyunsaturated homoallylic alcohols

Catalytic enantioselective vinylogous aldol reactions using extended enolates are of prominent value in synthetic organic chemistry. Here, we report our advances in the development of enantioselective bis-vinylogous and hyper-vinylogous Mukaiyama aldol reactions between a series of polyenylsilyloxy furans or polyenylsilyoxy indoles and aromatic aldehydes, realized by use of the enabling catalyst combination of silicon tetrachloride and Denmark’s chiral bis-phosphoramide base (R,R)-I. Several crucial issues such as the remote site-, enantio- and geometrical selectivity of the reaction will be highlighted, ultimately focusing on one main question: how far can we push the limits of the vinylogous reactivity transmittal?</i

The Mathematical description of lactation curves in dairy cattle

This review gives an overview of the mathematical modelling of lactation curves in dairy cattle. Over the last ninety years, the development of this field of study has followed the main requirements of the dairy cattle industry. Non-linear parametric functions have represented the preferred tools for modelling average curves of homogeneous groups of animals, with the main aim of predicting yields for management purposes. The increased availability of records per individual lactations and the genetic evaluation based on test day records has shifted the interest of modellers towards more flexible and general linear functions, as polynomials or splines. Thus the main interest of modelling is no longer the reconstruction of the general pattern of the phenomenon but the fitting of individual deviations from an average curve. Other specific approaches based on the modelling of the correlation structure of test day records within lactation, such as mixed linear models or principal component analysis, have been used to test the statistical significance of fixed effects in dairy experiments or to create new variables expressing main lactation curve traits. The adequacy of a model is not an absolute requisite, because it has to be assessed according to the specific purpose it is used for. Occurrence of extended lactations and of new productive and functional traits to be described and the increase of records coming from automatic milking systems likely will represent some of the future challenges for the mathematical modelling of the lactation curve in dairy cattle

<i>In vitro</i> and <i>in vivo</i> studies of artichoke extract (<i>Cynara scolymus</i> L.) as ketoprofen skin penetration enhancer

In this study, the enhancing effect of artichoke extract containing cynaropicrin on the in vitro and in vivo percutaneous absorption of ketoprofen from gels has been investigated

LRRK2 effect on dopamine receptor trafficking: implication in Parkinson’s disease

Parkinson disease is the second most common neurodegenerative disorder affecting 4 million people worldwide. It is characterized by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc) and by the presence of cytoplasmic inclusion bodies (Lewy bodies). Cell death leads to a profound depletion of dopamine neurotransmitter involved mainly in the control of the movement. Mutations in LRRK2 (leucine-rich repeat kinase 2) gene (PARK8; OMIM 609007) are responsible for one of the autosomal-dominant forms of Parkinson’s disease. Up to date, the LRRK2 biological function is largely unknown. LRRK2 has been found in different subcellular districts that play a crucial role in the control of vesicular trafficking: ER, Golgi apparatus and associated vesicles, cytoskeleton, lipid raft and lysosomes. The results of this work indicates that PD-associated mutant G2019S LRRK2 impairs dopamine receptor D1 internalization, leading to an alteration in signal transduction. Moreover, the mutant forms of LRRK2 affect dopamine receptor D2 turnover by decreasing the rate of the receptor trafficking from the Golgi complex to the cell membrane. Collectively, these findings are consistent with the conclusion that LRRK2 influences the motility of neuronal vesicles and the neuronal receptor trafficking

Nuove metodologie d'accesso alla diversità molecolare: sintesi di biomolecole e loro insiemi per un utilizzo in agricoltura e terapia

La nostra metodologia totalmente sintetica ed altamente flessibile indirizzata alla costruzione di piccole molecole organiche chirali, sia individuali, sia in miscela fra loro, prevede l’utilizzo di una triade omogenea di reagenti nucleofili eterociclici contenenti, rispettivamente, ossigeno, azoto e zolfo

Study of dissolution rate enhancement of poorly water soluble drug

Aim of this work is the preparation of spray-dried microspheres as drug delivery systems for Rokitamycin (RK), using chitosan (C) and its salt, chitosan glutamate (CG) to improve the dissolution rate of the drug. The work further aimed to investigate the effect of the type of chitosan and feed solution concentration on the microsphere properties