1,721,063 research outputs found
ENANTIOPURI, senza usare solventi ‘HH’
Full text linkGli amminoacidi con BnOH e p-TsOH in benzene o CCl4 a riflusso danno l’estere benzilico salificato enantiomericamente puro. Se si usa toluene, in sostituzione di questi solventi ‘highly hazardous’ (HH), l’estere racemizza. Il cicloesano è, invece, una valida alternativa: acido aspartico ed acido glutammico ne sono un esempio
Addressing Motor Dysfunction by a Selective α6-Containing Nicotinic Receptor Antagonist
Full text linkIn the striatum, presynaptic α6-containing nicotinic receptors are crucially involved in the modulation of dopamine release. CVN417, a novel selective antagonist at this receptor subtype, attenuates motor dysfunction in a Parkinson’s disease-relevant animal model, suggesting, for this pathology, a therapeutic strategy that could greatly profit from the restricted localization of α6* nicotinic receptors in the brain
Diastereomeric 2-aminomethyl-1,4-benzodioxane mandelates : phase diagrams and resolution
No full textThe diastereomeric salts of (R)- and (S)-2-aminomethyl-1,4-benzodioxane with unichiral mandelic acid form a simple eutectic, whose binary phase melting point diagram shows the unique eutectic at 0.35 M ratio of the less soluble diastereomer. Such an eutectic composition, near to 0.5, is consistent with the modest efficiency previously reported for their separation via crystallization from ethanol/ethyl acetate. However, the ternary solubility phase diagram, obtained from solubility measurements in methanol, shifts the eutectic to a lower molar ratio (0.10) of the less soluble diastereomer, thus indicating an optimal resolvability of the diastereomeric mandelates. This was confirmed by the highly efficient resolution of racemic 2-aminomethyl-1,4-benzodioxane with (R)-mandelic acid via a single crystallization from methanol. The ready availability of both the racemic substrate and the resolving acid makes this simple and efficient resolution procedure very attractive to obtain the enantiomers of 2-aminomethyl-1,4-benzodioxane, which are important synthetic intermediates
A short entry to enantiopure 2-substituted 1,4-benzodioxanes by efficient resolution methods
No full text(R)-1,4-Benzodioxane-2-carboxilic acid (R)-1 was obtained by resolution of the racemic acid 1 with stoichiometric or nonstoichiometric (+)- dehydroabietylamine (+)-2 in high chemical yield and enantiomeric excess. (S)-1 was isolated from the mother liquors of the crystallisation of (R)-1·(+)-2 and its enantiomeric excess maximised by recrystallisation procedures involving a precipitation under kinetic control or, alternatively, by conversion into the methyl ester followed by a single crystallisation. The different mechanisms of the two S enrichments is well explained by the binary phase diagrams of the acid and of the ester, which show that the former is a racemic compound, whereas the latter a conglomerate. The DSC analyses were extended to 2-hydroxymethyl- and 2-mesyloxymethyl-1,4-benzodioxane, establishing that the alcohol forms a racemic compound, while its mesyl ester a conglomerate. On the basis of these results, different resolution strategies can be designed to obtain useful homochiral 2-substituted 1,4-benzodioxanes coupling the resolution of 1 via diastereomeric salt formation with the enantiomeric enrichments by recrystallisations, preferably of its conglomerate forming derivatives
Processo di risoluzione di un sale della carnitinammide
No full textA process for the resolution of (D,L)-carnitinamide (D,L-I) chloride in its enantiomers (D-I) and (L-I), characterized in that a supersaturated solution or suspension of (D,L-I) in a suitable solvent or mixture of solvents, optionally added with a surfactant, is used. A series of alternate preferential crystallizations is carried out after adding minimum amount of seeds of one of the two enantiomers, (D-I) or (L-I), that is to be precipitated, and subsequently restoring the supersaturation conditions by adding an appropriate amount of (D,L-I) racemate
Pyrrolidinyl benzofurans and benzodioxanes: Selective α4β2 nicotinic acetylcholine receptor ligands with different activity profiles at the two receptor stoichiometries
Full text linkA series of racemic benzofurans bearing N-methyl-2-pyrrolidinyl residue at C(2) or C(3) has been synthesized and tested for affinity at the α4β2 and α3β4 nicotine acetylcholine receptors (nAChRs). As previously reported for the benzodioxane based analogues, hydroxylation at proper position of benzene ring results in high α4β2 nAChR affinity and α4β2 vs. α3β4 nAChR selectivity. 7-Hydroxy-N-methyl-2-pyrrolidinyl-1,4-benzodioxane (2) and its 7- and 5-amino benzodioxane analogues 3 and 4, which are all α4β2 nAChR partial agonists, and 2-(N-methyl-2-pyrrolidinyl)-6-hydroxybenzofuran (12) were selected for functional characterization at the two α4β2 stoichiometries, the high sensitivity (α4)2(β2)3 and the low sensitivity (α4)3(β2)2. The benzene pattern substitution, which had previously been found to control α4β2 partial agonist activity and α4β2 vs. α3β4 selectivity, proved to be also involved in stoichiometry-selectivity. The 7-hydroxybenzodioxane derivative 2 selectively activates (α4)2(β2)3 nAChR, which cannot be activated by its 5-amino analogue 4. A marginal structural modification, not altering the base pyrrolidinyl benzodioxane scaffold, resulted in opposite activity profiles at the two α4β2 nAChR isoforms providing an interesting novel case study
Green Oxidation of Heterocyclic Ketones with Oxone in Water
Full text linkThe recently reported efficient conversion of cyclic ketones to lactones by Oxone in neutral buffered water is extended to heterocyclic ketones, namely, cyclic N-Boc azaketones and oxoethers with the aim of obtaining N-protected azalactones and their analogues with oxygen in place of nitrogen. N-Boc-4-piperidinone and all the cyclic oxoethers were successfully oxidized to lactones, while the azacyclic ketones with nitrogen α-positioned to carbonyl were univocally transformed into N-Boc-ω-amino acids and N-Boc-N-formyl-ω-amino acids operating in alkaline water and DMF, respectively
4-, 5-, 6-, and 7-Hydroxybenzofuran: a unified strategy for a two-step synthesis of versatile benzofuranic building blocks
Full text linkOver several decades, many different strategies have been reported to prepare 4-, 5- , 6-, and 7- hydroxybenzofuran (HBF), which are very important synthetic intermediates. Interested in addition of their 2- lithiated O-protected derivatives to transient 1-pyrroline as a straightforward way to nicotinoids, we have developed a unique two-step procedure to obtain 4-, 5- , 6-, and 7-HBF from 2,6-, 2,5-, 2-4- and 2,3- dihydroxyacetophenone, respectively, by conversion into 4-, 5-, 6- and 7-hydroxybenzofuranone and successive reduction of these latter with lithium borohydride. On the basis of the overall yields, the number of steps and the availability of the starting materials, such a synthetic strategy can be advantageously compared with the literature methods, here briefly reviewed, developed to synthesize the four HBFs.(piture presented
Green Oxidation of Ketones to Lactones with Oxone in Water
Full text linkCyclic ketones were quickly and quantitatively converted to 5-, 6- and 7-membered lactones, very important synthons, by treatment with Oxone, a cheap, stable, and non-pollutant oxidizing reagent, in 1M NaH2PO4/Na2HPO4 water solution (pH 7). Under such simple and green conditions, no hydroxyacid was formed thus making unnecessary the adoption of more com-plex and non-ecofriendly procedures previously developed to avoid lactone hydrolysis. With some changes, the method was successfully applied also to water insoluble ketones such as adamantanone, acetophenone, 2-indanone and challenging cy-cloheptanone
From carnitinamide to 5-aminomethyl-2-oxazolidinones
No full textCarnitinamide chloride, an immediate synthetic precursor of carnitine, was chlorinated at the amide nitrogen. The resultant carnitinechloramide chloride, when treated with a base, revealed that the first-formed isolable and characterisable carnitinechloramide inner salt undergoes solid state conversion into 5-trimethylammoniomethyl-2-oxazolidinone chloride via Hoffmann rearrangement and intramolecular cyclization of the β-hydroxyisocyanate. The trimethylaminomethyl substituent at C-5 of the 2-oxazolidinone was converted into a dimethylaminomethyl group by microwave-assisted demethylation in DMF and then into a methylaminomethyl group by decomposition of the α-chloroethyl carbamate obtained by treatment with α-chloroethyl chloroformate. This sequence of reactions was then applied to both (S)- and (R)-carnitinamide chloride without any racemization to yield both enantiomers of 5-aminomethyl-2-oxazolidinones that are mono-, di- and tri-methylated at the exocyclic nitrogen
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