Treatment of epoxides with bis(trimethylsilyl)-selenide under strictly controlled conditions allows to isolate b-hydroxy selenols which evidence an unexpected stability, taking into account their known propensity to afford diselenides. Also thiiranes and aziridines lead to functionalized selenols bearing a thiol and a N-Ts-or N-Boc-protected amino moiety on b-position. These selenols were stable enough to react with different electrophiles. Ab-initio DF calculations on two suitable model systems, n-propyl selenol and bhydroxy derivative, allow to ascribe the observed low tendency to oxidation to noncovalent interactions between the selenol moiety and the ÀOH group.

The modulation of collagen turnover can be a relevant pharmacological target in the context of treating either pathological or pathophysiological conditions, such as collagen-related diseases and skin aging. Our recent work has focused on the search for short-chain peptides as lead compounds for further development of compounds that enhance the production of type I collagen. In this study we selected and synthesized overlapping peptides of the C-terminal portion of serpin A1 (residues 393-418), the impact of which on collagen production has been reported previously, in order to identify shorter and still active fragments and to provide insight on the mechanisms involved. The biological activity of each fragment was evaluated with cultured normal human dermal fibroblasts, and changes in the amounts of collagen were monitored in collected culture media by a sandwich ELISA technique developed in house. Interestingly, we identified a decapeptide, termed SA1-III (Ac-MGKVVNPTQK-NH2 ), as a promising candidate for our purposes; it is able to induce a significant increase in type I collagen levels in the culture medium of treated cells at micromolar concentrations.

3-Bromopropenyl methyl carbonate reacts smoothly with aldehydes in the presence of zinc in a mixture of saturated aqueous NH 4 Cl and THF (9:1). Monoprotected alk-1-en-3,4-diols are formed in high yields and in short reaction times. The reaction is diastereoselective, saturated aldehydes afford anti-adducts, while a,b-unsaturated and aromatic aldehydes preferentially give the synisomers. Very simple conditions for the conversion of intermediate monocarbonate derivatives of alk-1-en-3,4-diols to cyclic carbonates are also reported.Twenty years have passed since the seminal work of Pétrier and Luche on the allylation of aldehydes in aqueous media using organozinc reagents formed in situ. Allylic bromides were reacted in a Barbier-type protocol, using a mixture of saturated aqueous NH 4 Cl and THF as the solvent and zinc as the metal, to give homoallylic alcohols in almost quantitative yields (> 95%) and short reaction times (30-45 min). 1 In 2001 the Presidential Green Chemistry Challenge Award (academic category) was won by Li for his important contribution in the field of Grignard/Barbier reactions using allylic halides and indium in water and in air. 2 In recent times water as a solvent or co-solvent for organometallic chemistry has been thoroughly investigated 3 and expanded, for example, in palladium-catalyzed cross-coupling reactions 4 and in Lewis acid promoted processes. 5 Water, the archetypical green solvent, is not only low cost, non-toxic, and a safer solvent, compared with commonly used organic solvents, 6 but often affords different results such as increased reactions rates, for example in pericyclic cycloadditions, or modified selectivities. 7 We recently proposed a new protocol for the a-hydroxy allylation of carbonyl compounds in aqueous solvents, using 3-bromopropenyl acetate 1 as the precursor of a heterosubstituted allylic organometallic species, thus opening a route to alk-1-en-3,4-diols 2 (Scheme 1). 8 The diastereochemical outcome of this reaction was unprecedented among alternative hydroxyallylation reagents; 9 indeed, saturated aldehydes mainly afforded anti-adducts while aromatic or a,b-unsaturated aldehydes led to synadducts. Scheme 1The reaction of 1 with metallic zinc in saturated aqueous ammonium chloride solutions is very rapid at room temperature, and if an aldehyde is present, the corresponding diols 2 are obtained in very good yields (60-90%) after hydrolysis and purification by flash chromatography. Hydrolysis of the intermediate ester functionality to free alk-1-en-3,4-diols 2 is advisable, owing to the occurrence of both intramolecular (Path a, Scheme 2) and intermolecular (Path b, Scheme 2) transesterification reactions involving the intermediate alkoxide 3, leading to a number of adducts, as outlined in Scheme 2. Scheme 2In principle, the desired monoprotected product 6 could be obtained in high yields if quenching of the intermediate zinc alkoxide 3 with water (Path c) is faster than the transesterification processes (Paths b and c). The idea of lowering the carbonyl electrop...

Rett syndrome (RTT), a neurodevelopmental disorder affecting exclusively (99%) female infants, is associated with loss-of-function mutations in the gene encoding methyl-CpG binding protein 2 (MECP2) and, more rarely, cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1). In this study, we aimed to evaluate the function of the immune system by measuring serum immunoglobulins (IgG and IgM) in RTT patients (n = 53) and, by comparison, in age-matched children affected by non-RTT pervasive developmental disorders (non-RTT PDD) (n = 82) and healthy age-matched controls (n = 29). To determine immunoglobulins we used both a conventional agglutination assay and a novel ELISA based on antibody recognition by a surrogate antigen probe, CSF114(Glc), a synthetic N-glucosylated peptide. Both assays provided evidence for an increase in IgM titer, but not in IgG, in RTT patients relative to both healthy controls and non-RTT PDD patients. The significant difference in IgM titers between RTT patients and healthy subjects in the CSF114(Glc) assay (P = 0.001) suggests that this procedure specifically detects a fraction of IgM antibodies likely to be relevant for the RTT disease. These findings offer a new insight into the mechanism underlying the Rett disease as they unveil the possible involvement of the immune system in this pathology.

A facile and simple organocatalytic procedure to generate optically active 6-alkyl- and 6-aryl-substituted bicyclo[2.2.2]oct-5-en-2-ones is presented. The reaction is catalysed by a 9-amino-9-deoxyepiquinine trifluoroacetic acid salt, which activates alpha,beta-unsaturated cyclic ketones for the 1,4-addition of beta-keto benzothiazoyl sulfones in a stereoselective fashion. Subsequent intramolecular aldol reaction and Smiles rearrangement gives rise to important optically active bicycles, which are a common motif in natural products, ligands in asymmetric catalysis and substrates for Cope rearrangements, photochemical reactions, radical cyclisations and metathesis. Different bicyclic structures were obtained by utilisation of various cyclic enones or by performing ring-expanding reactions. Furthermore, two possible mechanistic pathways are outlined and discussed.