Current Organic Chemistry - Volume 16, Issue 22, 2012

The D3-trishomocubane is a unique high symmetrical chiral stabilomeric compound. Its derivatives have great potential to be used as scaffolds for drugs, in structure-oriented design, asymmetric catalysis, light-driven systems and much more. Axial substitution is the most useful method for this purpose but the least studied. This paper critically analyzes various synthetic strategies aiming at introducing substituents into C2/C9 positions of D3-trishomocubane. Herein we cover formation of trishomocubane skeleton and rearrangement of Cs-trishomocubanes. Based on a comprehensive retrosynthetic analysis a general synthetic scheme is proposed.

Hydrogen peroxide is a substrate or side-product in many enzyme-catalyzed reactions. For example, it is a side-product of oxidases, resulting from the re-oxidation of FAD with molecular oxygen, and it is a substrate for peroxidases and other enzymes. However, hydrogen peroxide is able to chemically modify the peptide core of the enzymes it interacts with, and also to produce the oxidation of some cofactors and prostetic groups (e.g., the hemo group). Thus, the development of strategies that may permit to increase the stability of enzymes in the presence of this deleterious reagent is an interesting target. This enhancement in enzyme stability has been attempted following almost all available strategies: site-directed mutagenesis (eliminating the most reactive moieties), medium engineering (using stabilizers), immobilization and chemical modification (trying to generate hydrophobic environments surrounding the enzyme, to confer higher rigidity to the protein or to generate oxidation-resistant groups), or the use of systems capable of decomposing hydrogen peroxide under very mild conditions. If hydrogen peroxide is just a side-product, its immediate removal has been reported to be the best solution. In some cases, when hydrogen peroxide is the substrate and its decomposition is not a sensible solution, researchers coupled one enzyme generating hydrogen peroxide “in situ” to the target enzyme resulting in a continuous supply of this reagent at low concentrations thus preventing enzyme inactivation. This review will focus on the general role of hydrogen peroxide in biocatalysis, the main mechanisms of enzyme inactivation produced by this reactive and the different strategies used to prevent enzyme inactivation caused by this “dangerous liaison”.

This review provides a survey on the reactions of nitrilimines, generated in situ by dehydrohalgenation of the corresponding hydrazonoyl halides, with heterocyclic enones. These reactions proved useful for synthesis of various spiroheterocycles possessing chiral centers and some biological activities.

Progress in study on coumarin-derived fluorescent chemosensors for metal ions was reviewed. Structures, synthetic methods, and recognition mechanism of coumarin-based probes were introduced and fluorescent recognition behavior of the probes toward various metal ions (Hg2+, Cu2+, Zn2+, Fe3+, Mg2+, Pb2+, Ag+, Ni2+, alkali metal ions, Ca2+, Cr3+, Ba2+, Cd2+, Al3+, As3+, Co2+, and Au3+) was outlined. Development trends in coumarin-derived fluorescent chemosensors were proposed.

In this study, the shape memory behaviour of poly(ε-caprolactone) (PCL) with different crosslinking degrees was investigated. PCL was first functionalised with maleic anhydride (MA) and glycidyl methacrylate (GMA), and successively chemically crosslinked by hexamethylene diisocianate (HMDI). The crosslinking reaction was studied through with a rotational stress rheometer, while the shape memory behaviour was analyzed with cyclic thermomechanical experiments and optical microscopy. The results show that the new materials exhibit good shape memory behaviour and good stability of the shape recovery under consecutive cycles in the range 55 - 70°C, can reach high level of stretching, and are furthermore characterised by high recovery speed. These results are promising for potential practical applications, as biomaterials for embolic devices in minimally invasive surgery.

Traditional medicine of Brazilian central savannah preconizes Dipteryx alata extracts against snakebites venoms. Previous studies have shown the extract of this plant's bark antagonizing the neuromuscular blockade caused by snake venom in isolated mice diaphragm and phrenic nerve models. In the present study, the triterpenoids lupeol, lupenone, 28-OH-lupenone and betulin, which are constituents of the plant, were observed by using in vitro pharmacological tests. These tests showed the efficacy of all tested triterpenoids (1 mg/5mL) against the irreversible neuromuscular blockade caused by snake venom from Bothrops jararacussu (Bjssu, 40 μg/mL, n=19), as following: betulin (68 ± 7%, n=11) ∼ lupeol (70 ± 8%, n=5) > lupenone (45 ± 9%, n=7) ∼ 28-OH-lupenone (54 ± 5%, n=4). Betulin (39.5 ± 9%, n=9) and lupenone (49.5 ± 8%, n=4) significantly protected against Crotalus durissus terrificus (CDT, 10 μg/mL, n=10) envenomation of neuromuscular junction. The mixture of betulin or lupeol + Bjssu venom and betulin or lupenone + CDT venom showed significant phytochemical protection in morphological analysis. Considering both pharmacological and morphological results, betulin showed the best protective effect against neuromuscular blockade and myotoxicity caused by both snake venoms. In addition, it has a potent short-term excitatory action in the neuromuscular junction. We concluded that the studied triterpenoids, especially betulin, showed antiophidian properties.

Studies on the Pd-catalyzed hydroarylation reaction of a library of differently substituted norbornene amino acid derivatives with numerous halogenoarenes are described. The effect on the regiochemistry of remote substituents, arylating agents and reaction conditions was considered. The reaction occurred with moderate to good yields and a moderate level of regioselectivity being the coupling at C-5 favorite.

Many bioactive compounds contain 2-furanoyl moieties. Classical Friedel-Crafts acylation conditions fail completely in the case of the sensitive and polymerization-prone furan, or give only rather unsatisfying yields only. The heterogeneous catalyst couple consisting of equimolar amounts of the stable and non-hygroscopic heteropolyacid aluminum dodecatungstophosphate (AlPW12O40)1 in combination with Mg(OH)2 was used for the direct reaction between furan and a variety of free carboxylic acids to regioselectively produce 2-furyl-alkylketones and 2-furyl-arylketones in good to excellent yields. The approach worked even in cases of labile benzofuran and indole derivatives where all alternative approaches failed.

A new family of non-ionic amphiphilic dendro-calix[4]arene bearing hydrophilic branched substituents at the upper rim and lipophilic alkyl chains at the lower rim was designed and synthesized. Micelles of various sizes are obtained due to the amphiphilic nature of the calix[4]arene derivatives in aqueous medium. The amphiphilic calix[4]arene derivatives effectively load hydrophobic dye such as alizarin yellow via secondary interactions such as hydrogen bonding and π-π stacking. The length of alkyl chain and the intrinsic cyclic nature of calixarene scaffold have shown a significant impact on the transport potential of all amphiphiles.