Volume 88, Issue 4

In enantioselective reactions, the major, desired enantiomer is commonly obtained along with the minor, undesired enantiomer. By continuous recycling of this undesired enantiomer back to starting material, products with improved enantiomeric purity can be obtained. Such in situ minor enantiomer recycling can be accomplished by coupling the catalytic reaction to an exergonic transformation of a sacrificial reagent. The method has been applied to the synthesis of O -acylated cyanohydrins, which serve as starting materials for a variety of biologically active compounds.

8-Dimethylaminonaphthalene-1-carbaldehyde reacts readily at 0°C with benzoyl or pivaloyl chloride by O-acylation and formation of a N–C bond (1.566(2)–1.568(3) Å) between the peri -substituents to give a salt. The reaction is promoted by electron donation from the dimethylamino group to the carbonyl group, akin to the properties of an amide. In contrast, the corresponding methyl ester and N,N-diisopropylamide react with acid in ether by protonation of the dimethylamino group and formation of a hydrogen bond to the carbonyl group, while under similar conditions the N,N-dimethylamide undergoes ready hydrolysis to the acid. The structures of products are determined by X-ray crystallography, and from the latter hydrolysis crystals containing zwitterionic 1-dimethylammonium-naphthalene-8-carboxylate and the corresponding O-protonated cation along with dimethylammonium and triflate ions were obtained.

We present recent advances in the understanding of the reduction of optically pure hydroxyalkylphosphinates and phosphine oxides, which represent key intermediates for the preparation of P-stereogenic ligands. Their reduction leads to P-chiral phosphinites and phosphines, respectively, and occurs stereospecifically with inversion of configuration using BH 3 ·THF, which plays three roles: activating, reducing and protecting agent. The formation of by-products as hydroxyalkyl secondary phosphine–boranes has also been studied.

Novel 5-(2,4-difluorophenoxy)-3-aryl-1,3,4-oxadiazol-2(3 H )-ones were prepared and in vivo SAR are discussed. Ionisable substituents on the N -phenyl ring provided compounds with significantly improved aqueous solubility. In addition, these analogues retained equivalent or improved potency against FAAH enzyme compared to the parent phenols 2–3 . FAAH inhibition by the 2-(piperazin-1-yl)ethyl and 3-(piperazin-1-yl)propyl derivatives 24 and 30 was confined to the periphery in mice (30 mg/kg), whereas hepatic FAAH activity was inhibited by over 90%.

Dihydrochalcones are polyphenols that exhibit a diversity of bioactivities, namely anti-inflammatory, antimicrobial and antiviral. We have explored the synthetic access to such molecular entities, and describe now an easy and scalable approach based on reduction of the olefinic double bond of chalcone precursors via in situ hydrogenation with the system Et 3 SiH-Pd/C in very high yield. The intermediate chalcones were synthesized also by a simple and efficient microwave-assisted Claisen–Schmidt condensation of aromatic aldehydes with acetophenones, conveniently protected with ethoxymethyl ether, if required. Chalcones were obtained as single reaction product in high yield in 2–3 h, while under conventional conditions at room temperature the reaction was carried out with completion only after 24 h. In addition, microwave irradiation has proven very efficient for deprotection of ethoxymethyl ether with iron chloride in only 10 min and very high yield.

The synthesis of new isonucleosides comprising purine and pyrimidine-derived systems linked to methyl glucopyranosidyl units at C-6 and evaluation of their cholinesterase inhibitory profiles is reported. Their access was based on the Mitsunobu coupling of partially acetylated and benzylated methyl glucopyranosides with purine and pyrimidine derivatives. While the reactions with purines and theobromine proceeded with complete regioselectivity, affording exclusively N 9 - or N 1 -linked 6′-isonucleosides, respectively, the use of pyrimidine nucleobases led to N 1 and/or N 3 -glucopyranosid-6′-yl pyrimidines and/or to N 1 ,N 3 /2- O ,4- O -pyrimidine-linked pseudodisaccharides through bis-coupling, depending on the substitution pattern of the sugar precursor and on the nature of the nucleobase. From this series of compounds, four were shown to be effective and selective inhibitors of acetylcholinesterase with inhibition constants in the micromolar concentration range. A tri- O -acetylated N 1 -glucopyranosid-6′-yl theobromine and a benzylated N 1 ,N 3 -bis-glucopyranosid-6-yl thymine were the most active molecules with K i values of 4 μM. A tri- O -benzylated glucopyranosid-6′-yl uracil displayed good and selective inhibition of butyrylcholinesterase ( K i =8.4±1.0 μM), similar to that exhibited by the standard galantamine. Molecular docking simulations, performed with the two most effective acetylcholinesterase inhibitors, showed interactions with key amino acid residues located at the enzyme’s active site gorge, which explain the competitive component of their inhibitory activities.

Selective product formation in the Pd-catalyzed cyclization of unsaturated amide and carboxylic acid derivatives is an intriguing and challenging task. We recently discovered that the oxidative intramolecular Pd(II)-catalyzed amination or oxylation of unsaturated N-sulfonyl carbamates, N-sulfonyl carboxamides and carboxylic acids takes place through the involvement of cyclic (usually, 5- or 6-membered) aminopalladated (A m PIs) or oxypalladated (O x PI) intermediates. Such cyclic intermediates can undergo a variety of transformations such as distocyclic β-H elimination, oxidative acetoxylation or intramolecular carbopalladation, depending upon the substrate and/or the reaction conditions. In the absence of appropriate reaction pathways, the cyclic nucleopalladated intermediates (N u PIs) simply engage in an inconsequential equilibrium with the initial substrate and other transformations occur such as allylic C–H activation or, in the particular case of allyl carbamates, [3,3]-sigmatropic rearrangement.

Various [O,O]- and [N,O]-spiroacetals were synthesized by gold-catalyzed spirocyclization of suitable functionalized alkynes. Whereas simple spiroacetals with two heteroatoms were readily obtained by regioselective cyclization of acetylenic diols or aminoalcohols, hitherto unknown spirocyclic isoxazolidines and pyrazolidines bearing three heteroatoms were formed by three-component coupling of alkynols, aldehydes, and protected hydroxylamine or hydrazine derivatives. The sustainability of these spirocyclizations was improved by using recyclable gold catalysts in water or nanomicelles as reaction medium.

A procedure is proposed to name new chemical elements. After the discovery of a new element is established by the joint IUPAC-IUPAP Working Group, the discoverers are invited to propose a name and a symbol to the IUPAC Inorganic Chemistry Division. Elements can be named after a mythological concept, a mineral, a place or country, a property or a scientist. After examination and acceptance by the Inorganic Chemistry Division, the proposal follows the accepted IUPAC procedure and is then ratified by the Council of IUPAC. This document is a slightly amended version of the 2002 IUPAC Recommendations; the most important change is that the names of all new elements should have an ending that reflects and maintains historical and chemical consistency. This would be in general “-ium” for elements belonging to groups 1–16, i.e. including the f-block elements, “-ine” for elements of group 17 and “-on” for elements of group 18.

Recommendations are given concerning the terminology relating to chemometrics. Building on ISO definitions of terms for basic concepts in statistics the vocabulary is concerned with mainstream chemometric methods. Where methods are used widely in science, definitions are given that are most useful to chemical applications. Vocabularies are given for general data processing, experimental design, classification, calibration and general multivariate methods.