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Herein, we show a comprehensive experimental, theoretical, and computational study aimed at designing macromolecules able to adsorb a cargo at the nanoscale. Specifically, we focus on the adsorption properties of star diblock copolymers, i.e., macromolecules made by a number f of H-T diblock copolymer arms tethered on a central core; the H monomeric heads, which are closer to the tethering point, are attractive toward a specific target, while the T monomeric tails are neutral to the cargo. Experimentally, we exploited the adaptability of poly(2-oxazoline)s (POxs) to realize block copolymer-coated nanoparticles with a proper functionalization able to interact with heavy metals and show or exhibit a thermoresponsive behavior in aqueous solution. We here present the synthesis and analysis of the properties of a high molecular mass block copolymer featured by (i) a polar side chain, capable of exploiting electrostatic and hydrophilic interaction with a predetermined cargo, and (ii) a thermoresponsive scaffold, able to change the interaction with the media by tuning the temperature. Afterward, the obtained polymers were grafted onto iron oxide nanoparticles and the thermoresponsive properties were investigated. Through isothermal titration calorimetry, we then analyzed the adsorption properties of the synthesized superparamagnetic nanoparticles for heavy metal ions in aqueous solution. Additionally, we use a combination of scaling theories and simulations to link equilibrium properties of the system to a prediction of the loading properties as a function of size ratio and effective interactions between the considered species. The comparison between experimental results on adsorption and theoretical prediction validates the whole design process.

We study the adsorption properties in bottlebrush/colloid binary mixtures by combining scaling theories, theoretical predictions, self-consistent field computations (SCFC), and molecular dynamics simulations. In particular, we focus on adsorption in the case in which an attraction is set between the two species, by analysing the solution properties for a range of interactions and the size ratio between colloids and bottlebrushes, in the case in which colloids are smaller than the macromolecules. We show that the onset of adsorption is dominated by the local properties of the adsorbing guest particle. This allows us to use the local similarity between a cylindrical bottlebrush and a spherical star polymer to predict the region of the parameter space in which the adsorption takes place. By employing simple scaling arguments, we thus extend the analytical results on the adsorption obtained for binary mixtures of star polymers/colloid nanoparticles. We then validate our predictions with molecular dynamics simulations. Moreover, by means of SCFC, we assess the adsorption-to-depletion transition of nanoparticles in polymeric bottlebrushes. Our results pave the road towards a smart rational design and coarse-graining of adsorbing/releasing systems, where an elongated shape might play an important role.

Cantharidin (CTD) is a defensive compound autogenously and exclusively produced by two phylogenetically related beetle families: Meloidae and Oedemeridae. Although this molecule usually acts as a strong deterrent against potential predators and parasites, some arthropod species, collectively named ‘canthariphilous species’, are attracted to CTD. Some species can sequester CTD from the CTD-producing species, using it as a chemical defense against enemies. The present paper focuses on the first-ever description of canthariphilous interactions between a checkered beetle species (Coleoptera: Cleridae) and a CTD -producing species. Field observations revealed individuals of the phytophagous beetle Tilloidea transversalis (Charpentier, 1825) (Coleoptera: Cleridae) biting individuals of the blister beetle Lydus trimaculatus (Fabricius, 1775) (Coleoptera: Meloidae). Laboratory behavioral experiments followed to verify if this peculiar behavior of T. transversalis also occurs on other co-occurring species. Moreover, chemical analyses were performed to assess whether T. transversalis can sequester CTD. Our results show that T. transversalis only attacks CTD-producing species. However, while chemical analyses prove that T. transversalis can sequester CTD from the hemolymph of L. trimaculatus, some clues (based on a CTD-baited traps sampling) suggest that this beetle, contrarily to other canthariphilous species, does not appear to show a high attraction to pure synthetic CTD. Thus, other unknown signals, alone or in combination with CTD, could be implicated in triggering the canthariphilous behaviors of T. transversalis.

Acinetobacter baumanni, is an opportunistic nosocomial multi-drug resistant bacterium, which represents a threat for human health. This pathogen is able to persist in intensive care units thanks to its extraordinary resistance towards dehydration, whose mechanisms are unknown and enable it to easily spread through surfaces, contaminating also medical devices. In this article we reveal, with a multimodal approach, based on μ-R Spectroscopy, Gas Chromatography coupled to Mass Spectroscopy, Atomic Force Microscopy and Fluorescence Recovery After Photobleaching, the bio-physical mechanisms that the membrane of two A. baumannii strains undergoes during dehydration. Showing a substantial decoupling of the phase transition from liquid crystalline to gel phase from evidence of cell lysis. Such decoupling may be the core of the resistance of A. baumannii against dehydration and highlights the different ability to resist to drought between strains.

Since 1966, when the poly(2-oxazolines) (POx) were discovered, they have undoubtedly been recognized as a polymer class with high synthetic versatility and good biocompatibility, giving access to highly functional and adaptable materials. The poly(2-oxazolines) are prepared through cationic ring-opening polymerization (CROP), which allow for simple control of the reaction condition, mainly due to the absence of undesired termination and even chain transfer are suppressed. Furthermore, the large available number of monomers with different side chain modifications opens the path towards the fabrication of innovative smart materials with a manifold of applications. Taking into account such observations, we envisage the possibility of designing and synthesizing a block-copolymer featured by: (i) a polar side chain (Fragment A), able to trap organic and/or inorganic compounds (e.g. heavy metal in wastewater or active principles for drug delivery applications); (ii) a thermoresponsive scaffold (Fragment B), able to change the interaction with the media by tuning the temperature. Subsequently, we intend to graft these polymers onto iron oxide nanoparticles (high grafting density) or on organic cores. Pursuing this research, herein we report our results involving the synthesis of the two Fragments (A and B) and the consequent grafting system to the nanoparticles. Finally, we point out the test for heavy metal binding in combination with the thermoresponsive behaviour of our products.

This work reviewed the state of the art concerning solar cookers and dryers used in food processing. The general description of solar cookers and dryers was presented, with a specific attention to the equipment where the cooking takes place with the contribution of the direct sunlight. Some insight about the history of design and development of devices that use solar light to process food were provided. The possibility to store the heat produced by solar light using Phase Change Materials was analyzed. Moreover, some “case-studies” were revised and discussed, in which solar light is efficiently used to dry or cook food, focusing on the quality of the food in terms of nutraceuticals content. The analyzed literature points out the necessity for further research about the effects produced by direct solar rays on different foods. The reliable data on this aspect will allow assessment of the quality of food transformation by solar cookers and dryers, adding a strong incentive to the development of such devices, up to now primarily motivated by energy-saving and environmental issues.

Background Meloidae (blister beetles) are known to synthetize cantharidin (CA), a toxic and defensive terpene mainly stored in male accessory glands (MAG) and emitted outward through reflex-bleeding. Recent progresses in understanding CA biosynthesis and production organ(s) in Meloidae have been made, but the way in which self-protection is achieved from the hazardous accumulation and release of CA in blister beetles has been experimentally neglected. To provide hints on this pending question, a comparative de novo assembly transcriptomic approach was performed by targeting two tissues where CA is largely accumulated and regularly circulates in Meloidae: the male reproductive tract (MRT) and the haemolymph. Differential gene expression profiles in these tissues were examined in two blister beetle species, Lydus trimaculatus (Fabricius, 1775) (tribe Lyttini) and Mylabris variabilis (Pallas, 1781) (tribe Mylabrini). Upregulated transcripts were compared between the two species to identify conserved genes possibly involved in CA detoxification and transport. Results Based on our results, we hypothesize that, to avoid auto-intoxication, ABC, MFS or other solute transporters might sequester purported glycosylated CA precursors into MAG, and lipocalins could bind CA and mitigate its reactivity when released into the haemolymph during the autohaemorrhaging response. We also found an over-representation in haemolymph of protein-domains related to coagulation and integument repairing mechanisms that likely reflects the need to limit fluid loss during reflex-bleeding. Conclusions The de novo assembled transcriptomes of L. trimaculatus and M. variabilis here provided represent valuable genetic resources to further explore the mechanisms employed to cope with toxicity of CA in blister beetle tissues. These, if revealed, might help conceiving safe and effective drug-delivery approaches to enhance the use of CA in medicine.

In cultural heritage field, significant research efforts have been recently made to improve the efficacy of anti-vegetative treatments and to reduce the environmental impact caused by biocides high concentration. According to the pro-ecological approach, this work reports a novel approach based on the encapsulation/incorporation of environmentally-friendly biocides in different silica nanosystems in order to control the development of biological patinas on outdoor cultural heritage. Two different green biocides have been selected and tested in silica nanosystems: the zosteric acid sodium salt (ZS), a natural antifoulant compound produced by Zostera marina (eelgrass), and the usnic acid (UA), a secondary metabolite produced by some saxicolous lichens. ZS was previously successfully encapsulated but never entrapped in mesoporous silica; instead, UA is, for the first time, encapsulated and in situ entrapped into the silica nanosystems in order to control the release over time. Both silica nanosystems have been characterized as far as their dimensions and superficial properties and loading capability. The antifouling activity was assessed against microorganisms from biopatinas colonising the Aurelian Walls in Rome. Our results have shown that the two nanosystems have complementary properties, thus it is possible to tune the antifouling efficiency by combining the two in different proportions.

Blister beetles owe their name to their ability to release cantharidin, a blistering terpene, the highest concentration of which is retained in male accessory glands. The anatomy and ultrastructure of the three pairs of male reproductive accessory glands and the glandular region of the two vasa deferentia of Meloe proscarabaeus were investigated using light, electron and ion beam microscopy. All of the mesodermal glands here analysed share a common structural organization with an outer muscular layer and an inner glandular epithelium facing a broad lumen in which the secretory products are released. Developed rough endoplasmic reticulum, Golgi systems, abundant mitochondria, numerous secretory vesicles and a microvillated apical membrane are commonly found in the cells of different glandular epithelia, suggesting that all accessory gland pairs as well as the vasa deferentia are involved in an active synthesis. Nevertheless, each pair of glands appears specialized in the production of a specific set of substances, as suggested by the peculiarities in cellular ultrastructure and by the different aspect of the secretions stored in their glandular lumen. The above cited features of male accessory glands of M. proscarabaeus are compared with those of other beetles and some hints on their potential role in producing and/or concentrating cantharidin are provided.

New dihydroxytyrosyl esters 2a, 2c&ndash, 2j of dicarboxylic acids were synthesized from methyl orthoformate protected hydroxytyrosol 3 and diacyl chlorides. New compounds were characterized (HRMS, FT-IR, 1H- and 13C-NMR), and tested for antioxidant activity both in vitro (ABTS) and on L6 myoblasts and THP1 leukemic monocytes cell culture by DCF assay. According to the ABTS assay, compounds 2a, 2c&ndash, 2j showed a TEAC value of antioxidant capacity up to twice that of Trolox. Very high or complete ROS protections were obtained in the cell environment where lipophilicity and rigidity of dicarboxylic structure seem to facilitate the antioxidant effect. MTT assay and proliferation test were used for assessment of cell viability. These compounds can be envisaged as a new class of preservatives for food or cosmetic products.

Aziridines, the nitrogen counterparts of epoxides, are among the most challenging and intriguing heterocycles in organic chemistry since they not only represent the endpoints of several total syntheses as common scaffolds in natural products but also act as crucial precursors of complex molecules. The present review provides a brief overview of aziridine derivatives as well as the authors’ choice of published papers that highlight recent enhancements concerning asymmetric organocatalytic strategies involved in aziridination reactions.

We have applied techniques of quantum phase estimation to the dynamical tracking of the optical activity of a solution of sucrose undergoing acid hydrolysis. We adopt a multiparameter approach that makes the estimation reliable and robust against setup instabilities.

Quantum photonics has demonstrated its potential for enhanced sensing. Current sources of quantum light states tailored to measuring, allow to monitor phenomena evolving on time scales of the order of the second. These are characteristic of product accumulation in chemical reactions of technologically interest, in particular those involving chiral compounds. Here we adopt a quantum multiparameter approach to investigate the dynamic process of sucrose acid hydrolysis as a test bed for such applications. The estimation is made robust by monitoring different parameters at once.

Cantharidin (CA), a toxic terpene produced by blister beetles (Coleoptera: Meloidae), attracts the interest of many researchers for its renowned medical properties. The CA content in blister beetles has been mainly quantified in some Oriental species, due to their use in traditional Chinese medicine, or in few other species of toxicological importance. As CA quantification has been largely ignored in many other members of this family, we aimed at estimating CA content in natural populations of two of the most abundant species in central Italy, Mylabris variabilis and Lydus trimaculatus. Nearly 100 individuals for each species were collected in the field, identified and reared in fauna-boxes until CA collection. Available protocols were optimized for CA extraction from both dried-body tissues and exuded hemolymph collected from leg joints using capillary tubes. The CA content was quantified in a gas chromatography system coupled to a mass spectrometer using a calibration curve with diethyl-ester of norcantharidin as the internal standard. We observed: (i) high variability in CA content among specimens, which was positively related to individual dry-weight; and (ii) slightly larger (though non-significant) amount of CA in males than in females for both species. Our data are consistent with the available published reports about CA content, transfer and distribution in blister beetles and suggest a conserved biological role of this terpene in Meloidae.

In the attempt of satisfying the quest for new antifouling products tailored for applications on Cultural Heritage, we have synthesized and characterized two different silica nanosystems. The first consists of core-shell nanocapsules and the second one of mesostructured nanoparticles. Both systems have been successfully loaded in situ with the commercial biocide 2-mercaptobenzothizole (MBT). The synthesis procedure and particles characterization measurements, as far as their dimensions and superficial properties, loading capability, and release rate in aqueous solution, are reported. We stress that both particles have the dimensions required to avoid undesired light scattering once dispersed on the artefact surface. Interestingly, the two nanoparticles have complementary properties, suggesting that combining them in a coating may have a higher potential for production of new generation active products.

We employed the membrane of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes suspended in water as a microenvironment for carrying out the organocatalytic epoxidation of an α-alkylidene oxindole. The reaction proceeds smoothly and displays diastereo- and enantio-selectivity that differs from what is achieved under bulk solution conditions. The potential of organocatalytic approaches for synthetic transformations in aqueous phase in the presence of dispersed membranes is briefly discussed.

Quantum sensors must be robust against noise even when non-stationary. Here we study a dynamic process using a Multiparameter approach that gives us control of our setup instabilities.

This paper describes the development of an original micro-solid phase extraction device and its evaluation for the isolation of F2-isoprostanes (F2-IsoPs) from cord and maternal plasma samples. The unit is very simple and consists in a rotating disc (1.8 cm diameter) of oxidized buckypaper (BP), enwrapped in a polypropylene mesh pouch. Even if the selected F2-IsoPs have logP and pKa values that make them suitable candidates for their sorption on BP, several parameters were optimized to maximize recoveries: time of adsorption and desorption; stirring speed; volume, pH and ionic strength of the sample; type, volume, and fractions of the elution solvent; oxidation grade of BP. Among all, the last one was crucial in affecting extraction yields because of the analyte interactions with polar functionalities, introduced by a preliminary oxidative acid treatment. The investigation established the optimal oxidation time and highlighted the pros and cons of the acid activation step. All extracts were analyzed by means of liquid chromatography-tandem mass spectrometry (LC–MS/MS). Validation was performed according to the main FDA guidelines for bioanalytical methods. Depending on the spike level and analyte, recoveries ranged between 30 and 120% with precision and accuracy values lower than 20%. Quantitative analysis was accomplished by matrix-matched calibration curves whose determination coefficients were higher than 0.95. Lower limit of quantitation (LLOQ) spanned the range 2.45–6.77 μg L−1. The validated method was applied to the analysis of eight pairs of mother/child plasma samples, revealing the presence of 8-iso-15-keto-PGF2α and 8-iso-PGE2 at a concentration of about 10 μg L−1 in most cord plasma samples of preterm newborns.

Glaucoma affects millions of people worldwide and causes optic nerve damage and blindness. The elevation of the intraocular pressure (IOP) is the main risk factor associated with this pathology, and decreasing IOP is the key therapeutic target of current pharmacological treatments. As potential ocular hypotensive agents, we studied compounds that act on two receptors (serotonin 2A and adrenergic α

Taking into account the postulated reaction mechanism for the organocatalytic epoxidation of electron-poor olefins developed by our laboratory, we have investigated the key factors able to positively influence the H-bond network installed inside the substrate/catalyst/oxidizing agent. With this aim, we have: (i) tested a few catalysts displaying various effects that noticeably differ in terms of steric hindrance and electron demand; (ii) employed alpha-alkylidene oxindoles decorated with different substituents on the aromatic ring (11a-“g), the exocyclic double bond (11h-l), and the amide moiety (11m-“v). The observed results suggest that the modification of the electron-withdrawing group (EWG) weakly conditions the overall outcomes, and conversely a strong influence is unambiguously ascribable to either the N-protected or N-protected lactam framework. Specifically, when the NH free substrates (11m-“u) are employed, an inversion of the stereochemical control is observed, while the introduction of a Boc protecting group affords the desired product 12v in excellent enantioselectivity (97:3 er).

The present work aimed to synthesise promising antioxidant compounds as a valuable alternative to the currently expensive and easily degradable molecules that are employed as stabilizers in industrial preparation. Taking into account our experience concerning domino Friedel-Crafts/lactonization reactions, we successfully improved and extended the previously reported methodology toward the synthesis of 3,3-disubstituted-3H-benzofuran-2-one derivatives 9–20 starting from polyphenols 1–6 as substrates and either diethylketomalonate (7) or 3,3,3-trifluoromethyl pyruvate (8) as electrophilic counterpart. The antioxidant capacity of the most stable compounds (9–11 and 15–20) was evaluated by both DPPH assay and Cyclic Voltammetry analyses performed in alcoholic media (methanol) as well as in aprotic solvent (acetonitrile). By comparing the recorded experimental data, a remarkable activity can be attributed to few of the tested lactones.

Glaucoma affects millions of people worldwide, causing optic nerve damage and blindness. The elevation of the intraocular pressure (IOP) is the main risk factor associated with this pathology, and nowadays, the key therapeutic target of the existing pharmacological treatments. We studied, as potential ocular hypotensive agents, compounds acting on two receptors (serotonin 2A, 5-HT2A, and adrenergic ?1) linked to the regulation of the humour aqueous dynamic. In this article we describe the design, synthesis, and pharmacological profiling of a series of novel bicyclic and tricyclic 2N-alkyl-indazole-amide derivatives. The work brought to the identification of compound 28, a 3,4-dihydropyrazino[1,2-b]indazol- 1(2H)-one derivative, with potent 5-HT2A antagonism, >100 fold selectivity over other serotonin subtype receptors and high affinity for the ?1 receptor. Moreover, when administered locally, 28 showed superior ocular hypotensive action in vivo, compared to the clinically used reference compound timolol.

Hydroxylamine (HA) is an oxidant of ferrous globins and its action has been reported to be inhibited by CO, even though this mechanism has not been clarified. Here, kinetics of the HA-mediated oxidation of ferrous carbonylated Mycobacterium tuberculosis truncated hemoglobin N and O (Mt-trHbN(II)-CO and Mt-trHbO(II)-CO, respectively) and Campylobacter jejuni truncated hemoglobin P (Cj-trHbP(II)-CO), at pH 7.2 and 20.0 °C, are reported. Mixing Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO solution with the HA solution brings about absorption spectral changes reflecting the disappearance of the ferrous carbonylated derivatives with the concomitant formation of the ferric species. HA oxidizes irreversibly Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO with the 1:2 stoichiometry. The dissociation of CO turns out to be the rate-limiting step for the oxidation of Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO by HA. Values of the second-order rate constant for HA-mediated oxidation of Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO range between 8.8 × 104 and 8.6 × 107 M−1 s−1, reflecting different structural features of the heme distal pocket. This study (1) demonstrates that the inhibitory effect of CO is linked to the dissociation of this ligand, giving a functional basis to previous studies, (2) represents the first comparative investigation of the oxidation of ferrous carbonylated bacterial 2/2 globins belonging to the N, O, and P groups by HA, (3) casts light on the correlation between kinetics of HA-mediated oxidation and carbonylation of globins, and (4) focuses on structural determinants modulating the HA-induced oxidation proces.

Telaprevir is a direct acting antiviral agent, used with pegylated interferon and ribavirin for the management of chronic hepatitis C virus (HCV) genotype 1 infection, in patients not responding to therapy with pegylated interferon and ribavirin only. Although 75% of patients achieve a sustained virological response after treatment with telaprevir, adverse drug-drug interactions and undesirable events often occur. Therefore, telaprevir monitoring is pivotal to improve the management of HCV infection. Here, the first High-Performance Liquid Chromatography-Ultraviolet (HPLC-UV) method to quantify telaprevir in human plasma of HCV-genotype 1-infected patients is reported. The volume of the plasma sample was 700 μL. This method involved automated solid-phase extraction with Oasis HLB Cartridge 1 cc (divinylbenzene and N-vinylpyrrolidone). The extracted samples were reconstituted with 150 μL of 60/40 water/acetonitrile. Thirty microliters of these samples was injected into a HPLC-UV system, and the analytes were eluted on a X Terra(®) RP18 column (250 mm × 4.6 mm i.d.) with a particle size of 5 μm. The mobile phase (ammonium acetate buffer, 150 mM, pH 8.0, and methanol:acetonitrile 50:50) was delivered at 1.0 mL/min with linear gradient elution. The total run time for a single analysis was 16 min; telaprevir was detected by UV at 276 and 286 nm. The calibration curve was linear from 312.5 to 20,000 ng/mL (r(2) > 0.996). The absolute recovery of telaprevir ranged between 89 and 93% at concentrations of quality control samples of 800, 4,000, 8,000, and 16,000 ng/mL. Both precision and accuracy were always

An asymmetric domino Friedel–Crafts/lactonization sequence between phenols and trifluoropyruvate has been accomplished for the first enantioselective synthesis of ( S )-BHFF, a positive allosteric modulator (PAM) of GABA B receptor. The developed protocol leads to 3-OH-benzofuranone derivatives bearing a quaternary stereogenic center, and gives a valuable access to bioactive compounds with promising pharmaceutical applications.

International audience; An asymmetric domino Friedel–Crafts/lactonization sequence between phenols and trifluoropyruvatehas been accomplished for the first enantioselective synthesis of (S)-BHFF, a positive allosteric modulator(PAM) of GABAB receptor. The developed protocol leads to 3-OH-benzofuranone derivatives bearing aquaternary stereogenic center, and gives a valuable access to bioactive compounds with promising pharmaceuticalapplications

3-(Phosphorylmethylene)oxindoles have been prepared by a straightforward Horner-Wadsworth-Emmons reaction. They were treated with ethyl N-{[(4-nitrophenyl)sulfonyl]oxy]-carbamate (NsONHC0 2 Et) in the presence of CaO to afford new aziridine-2-phosphonates spiro-fused with oxindole. 3-(Phosphorylmethylene)oxindoles were also transformed into novel spiro[oxindole-oxiranes] by reaction with H 2 O 2 /NaOH.

This review provides the authors’ selection of recent publications that highlight the increasing efforts to develop valuable organocatalytic domino/tandem/cascade reactions as the main tool in the creation of quaternary stereocenters. 1 Introduction 2 Diarylprolinol Ethers and Proline Derivatives 3 Imidazolidinones 4 Bronsted Acids 5 Cinchona Alkaloids 6 Thioureas 7 Squaramides 8 N-Heterocyclic Carbenes 9 Outlook and Conclusions

This review provides the authors’ selection of recent publications that highlight the increasing efforts to develop valuable organocatalytic domino/tandem/cascade reactions as the main tool in the creation of quaternary stereocenters. 1 Introduction 2 Diarylprolinol Ethers and Proline Derivatives 3 Imidazolidinones 4 Bronsted Acids 5 Cinchona Alkaloids 6 Thioureas 7 Squaramides 8 N-Heterocyclic Carbenes 9 Outlook and Conclusions

Organocatalysis has appeared as a powerful tool to mediate highly complex transformations. It is a very recent field of research and in the last years has experimented a constant growth, where many scientists investigate the utilization of organocatalysts in order to pave the way to very impressive and outstanding combination of reactions in a one-pot process. Consequently, thoroughly the high flexibility of activation modes of organocatalysts, and their combination therefore, the construction of highly functionalized chiral complex molecules was made possible. In this book chapter, rather than an exhaustive detailed approach on organocatalyzed asymmetric MCRs, we gave an overall overview on selected remarkable examples. To date, an impressive number of organocatalyzed asymmetric MCRs have appeared, and due to the suitable combination of transformations, very challenging scaffolds were isolated in a single operation by combining very simple, almost always, commercially available, starting materials.

A valuable Lewis-acid-catalysed domino reaction involving a Friedel–Crafts alkylation of variously substituted phenols followed by a direct lactonization has been successfully developed (22 examples, yields up to 98 %). This protocol tolerates not only opposite electron demand substituents on the starting materials, but also drastic modifications of the alkylating agents, and gives direct access to the corresponding 3-hydroxy-benzofuran-2-ones, which could easily undergo further chemical transformation. The relevance of our method was further confirmed by the straightforward synthesis of rac-BHFF, the recently discovered and extremely promising positive allosteric modulator of the GABAB receptor.

N-Protected α-amino-α-vinyl-γ-butyrolactones 1 are obtained by the aza-Michael-type addition of NsONHCO2Et to novel silylated α-ylidene-γ-butyrolactones 2, through ring opening of the intermediate aziridine and loss of the trimethylsilyl group. The stereoselective synthesis of compounds 2, by cross-coupling reactions between α-[(triflyloxy)ylidene]-γ-butyrolactones 3 and tris[(trimethylsilyl)methyl]aluminum, is also described. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

We have discovered that α-[dimethyl(thexyl)silyl]acetaldehyde (= [dimethyl(1,1,2-trimethylpropyl)silyl]-acetaldehyde; 31) has a strong, woody odor. Structural analysis has shown resemblance to known odorants with similar organoleptic properties. On the basis of structure-odor relationships, new and more-powerful woody and ambery sila odorants were prepared. Further derivatization led to a set of compounds with very interesting organoleptic properties. Selected chiral compounds were also prepared stereoselectively. The influence of the absolute configuration on the olfactory properties was in agreement with theoretical assumptions. We also designed other groups of organosilicon odorants. The compounds discovered can be obtained in a few simple steps from commercially available reagents, and may find application in the fragrance and flavor industry. Their structures provide interesting data for further research on structure-odor relationships. © Verlag Helvetica Chimica Acta, Postfach, CH-8042 Zürich, Switzerland, 2005.