Tröger’s bases in the acronycine, benzo[a]acronycine, and benzo[b]acronycine series

Reaction of 11-aminoacronycine, 10-aminobenzo[a]acronycine, and 10-aminobenzo[b]acronycine with paraformaldehyde gave the corresponding Tröger’s bases 11, 14, and 16, respectively. The cytotoxic activity of those three new compounds was determined against L-1210 leukemia and KB-3-1 solid tumor cell lines, in comparison with their parent compounds, acronycine, benzo[a]acronycine, and benzo[b]acronycine.     

Irreversible cleavage of a carbene-rhodium bond in Rh-N-heterocyclic carbene complexes: implications for catalysis

Despite the generally accepted belief that carbene-metal bonds are strong and do not dissociate, the reaction of Rh-N-heterocyclic carbene complexes with triphenylphosphine in dichloroethane was determined to take place via cleavage of the Rh-carbene bond. The products of this reaction are Wilkinson’s catalyst and a bisimidazolium salt derived from reaction between dichloroethane and two equivalents of the carbene. The implications of this reaction for catalysis are significant since the carbene complex shows lower activity than Wilkinson’s catalyst in hydrogenation reactions. In non-halogenated solvents, the catalyst shows higher stability, such that the rate of exchange with free phosphine could be measured, and was determined to be ca. 10 times slower than in Wilkinson’s catalyst.     

Mechanism insights into an unexpected isomerisation reaction observed during conversion of N-benzyl piperazinones to corresponding N-benzyl thio-piperazinones

An interesting and surprising rearrangement was observed during the reaction of 4-N-benzyl piperazinone derivatives with Lawesson’s reagent as a thionating agent. Investigation into the possible mechanism responsible for these results is reported herein.     

Reactivity and regioselectivity in the synthesis of spiroindoles via indole o-quinodimethanes. An experimental and computational study

The 1,3-dipolar cycloaddition reactions of stable nitrile oxides with indole o-quinodimethanes have been examined. In all cases the ‘exo-anti’ addition products, dispiroisoxazolines, were isolated in moderate to good yields (25-47%). In addition, from the reaction of one of the indole quinodimethanes with mesitonitrile oxide the ‘exo-syn’ addition product was isolated in 7% yield along with the remarkable indole quinodimethane dimerization and cycloaddition product, which was isolated in 13% yield. An analogous dimerization and cycloaddition product was isolated in 18% yield from the reaction of the N-acetyl-indole quinodimethane with mesitonitrile oxide. In the case of the reaction of the N-benzoylindole quinodimethane with the 2,6-dichlorobenzonitrile oxide an oxime was also isolated in 13% yield. The proposed reaction mechanism is supported by semiempirical (AM1) MO calculations via FMO interactions. The observed selectivity was explained by an investigation of the transition states carried out also for analogous dispiroisoxazolines.     

Enantioselective aza-Diels-Alder reaction of Brassard’s diene with aldimines catalyzed by chiral N,N′-dioxide-Yb(OTf)3 complex

The chiral N,N′-dioxide-Yb(OTf)₃ complex-catalyzed enantioselective aza-Diels-Alder reaction of Brassard’s diene with aldimines has been developed, giving the corresponding α,β-unsaturated δ-lactam derivatives in moderate yields with good enantioselectivities (up to 81% ee and up to 99% ee by single recrystallization) under mild conditions. Isolation of the reaction intermediate indicates that this asymmetric aza-Diels-Alder reaction proceeds through a stepwise Mannich-type pathway.     

Protease inhibitors from three fishpond water blooms of Microcystis spp.

Four new natural products, micropeptin GH979 (1), microginin GH787 (2), micropeptin HM978 (3), and micropeptin HA983 (4), as well as 10 known protease inhibitors and hepatotoxins, were isolated from the hydrophilic extract of three samples of cyanobacteria (Microcystis spp.) that were collected from fishponds in Kibbutz Giva’at Haim, Kibbutz Hama’apil, and Kibbutz Gan Shmuel. The structures of the pure natural products were elucidated using spectroscopic methods, including UV, 1D and 2D NMR, and MS techniques. The absolute configuration of the chiral centers of the compounds was determined using Marfey’s method. The inhibitory activity of the compounds was determined for the serine proteases: trypsin, chymotrypsin, thrombin and elastase, and the metalloprotease, aminopeptidase N.     

Stereoselective synthesis of methyl branched chiral deoxypropionate units: a new route for synthesis of insect pheromone (−)-lardolure and (2R,4R,6R,8R) 2,4,6,8-tetramethylundecanoic acid

(−)-Lardolure and (2R,4R,6R,8R)-2,4,6,8-tetramethylundecanoic acid have been synthesized via lipase catalyzed desymmetrization strategy to create two methyl chiral centers. Other key steps involved in the synthesis are Wittig reaction, Evan’s asymmetric alkylation, Grignard reaction, Pd-catalyzed isomerization of primary allylic alcohol to corresponding saturated aldehyde, and PhNO/proline catalyzed MacMillan α-hydroxylation.     

N-tert-Butyl-N-chlorocyanamide: a new reagent for the efficient preparation of gem-chloronitroso compounds

A new reagent for the efficient preparation of gem-chloronitroso compounds has been developed. The reaction of ketoximes with N-tert-butyl-N-chlorocyanamide takes place instantaneously in carbon tetrachloride at room temperature with excellent yields under mild conditions.     

Synthesis and photochromic behaviour of new methyl induced linear and angular thieno-2H-chromenes

New methyl induced linear and angular thieno-2H-chromenes 4, 5 and 6 were prepared by reaction of new methylated 6-hydroxybenzo[b]thiophenes 2 (a, b and c) and propargylic alcohols 3a and 3b, using acidic Alumina Brockmann I as catalyst and drying agent. Compounds 2 were prepared in good to excellent yields in a ‘one pot’ three step reaction from the corresponding bromo compounds 1. The photochromic behaviour of compounds 4, 5 and 6b was evaluated with the aid of a classical set of spectrokinetic parameters, and compared to reference compounds that are benzoannellated in the 5,6 and 6,7 positions of the chromene (naphthopyrans) and also to thieno-2H-chromenes 7 and 8, previously prepared, which are analogues of 5a. The resistance to fatigue (photodegradation) under continuous irradiation was also evaluated.     

Diels-Alder reaction of optically active (E)-γ-keto-α,β-unsaturated p-tolylsulfoxides with cyclopentadiene

The Diels-Alder reaction of enantiomerically pure (E)-γ-keto-α,β-unsaturated p-tolylsulphoxides 3 with cyclopentadiene give four easily separable diastereomers. The effect of several Lewis acids on the reaction was studied, finding a high endo selectivity with respect to the carbonyl group and moderate π-diastereoselectivity using BF₃·Et₂O as catalyst. The reactivity of compounds 3 as well as their endo selectivity are both higher than those observed for the corresponding (E)-3-sulfinylacrylates.     

pTSA-catalyzed condensation of xylenols and aldehydes under solvent-free conditions: One-pot synthesis of 9H-xanthene or bisphenol derivatives

A simple and efficient procedure for the synthesis of 9H-xanthene or bisphenol derivatives has been developed by one-pot condensation of xylenols with aromatic aldehydes in the presence of p-toluenesulfonic acid (pTSA) as a catalyst under solvent-free conditions at 100 °C. It is noteworthy that the condensation reaction of 3,5-xylenol with aldehydes produces 9H-xanthene derivatives, while the reaction with other xylenols leads to the corresponding bisphenol derivatives. Different types of aromatic aldehydes are used in the reaction and in every case the products were obtained in good to excellent yields. The structures of these compounds were established on the basis of IR, ¹H NMR, ¹³C NMR and CHN data.     

Synthesis of cesium selective pyridyl azocalix[n]arenes

A series of pyridylazo calix[n]arenes (n=4, 6, 8) including the first examples of mixed hetroaryl azocalix(n)arenes have been synthesized by coupling calix[n]arenes with diazonium salts derived from amino pyridines. It has been observed that the coupling reaction of diazonium salt obtained from 3-aminopyridine with calix[n]arene gives tetrakis-, hexakis- and octakis (pyridylazo)calix[n]arenes (n=4,6,8) while those derived from 4-aminopyridine give partially substituted (4-pyridylazo)calix[n]arene analogs. There is no reaction of calix(n)arenes with diazonium salts derived from 2-aminopyridine under identical conditions of experiments. The conformational analysis of synthesized compounds have been ascertained by detailed spectral measurements and single crystal X-ray analysis of 5-(3′-pyridylazo)-25,26,27,28-tetrahydroxycalix[4]arene. A rational explanation for the observed partial and exhaustive coupling reaction in the synthesis of heteroaryl azocalix(n)arenes has been suggested. Preliminary evaluation of synthesized derivatives as molecular receptors for metal ions indicates that they have good potential to function as selective ionic filters for cesium ions.     

Two new microcyclamides from a water bloom of the cyanobacterium Microcystis sp.

Two new thiazole-containing cyclic hexapeptides, microcyclamides MZ602 and MZ568, were isolated from the hydrophilic extract of the cyanobacterium Microcystis sp. The structures of the pure natural products were elucidated using spectroscopic methods including UV, 1D and 2D NMR, and MS techniques. The absolute configuration of the chiral centres of the modified cyclic peptides was determined using Marfey’s method for HPLC. The microcyclamides have been evaluated for their cytotoxicity against leukemia cell lines and inhibition of serine proteases.     

Lewis acid catalyzed asymmetric halohydrin reactions of chiral α,β-unsaturated carboxylic acid derivatives with N-halosuccinimide (NXS) as the halogen source

Lewis acid catalyzed asymmetric halohydrin reactions—(halohydroxylation as well as halomethoxylation) of chiral α,β-unsaturated carboxylic acid derivatives were performed using N-halosuccinimide (NXS; X = Br, I) as the halogen source. Regio- and anti-selectivity of 100% and moderate to good diastereoselectivity with good yields were observed when Oppolzer’s sultam was used as the chiral auxiliary. Among the Lewis acids, Yb(OTf)₃ was found to be the best catalyst. Alkenoyl and cinnamoyl substrates smoothly underwent bromohydrin reactions and the more electron-rich cinnamoyl substrates preferred to undergo iodohydrin reactions. However, electron-deficient cinnamoyl substrates did not respond to this Lewis acid catalyzed halohydrin reaction with NXS (X = Cl, Br, I).     

Baker’s yeast catalyzed one-pot three-component synthesis of polyfunctionalized 4H-pyrans

Baker’s yeast catalyzed one-pot three-component cyclocondensation of aryl aldehydes, malononitrile, and β-dicarbonyls in organic medium has been carried out to obtain polyfunctionalized 4H-pyrans. The reaction has been carried out at room temperature in organic solvent, dimethylacetamide and the products obtained in good to moderate yields with simple work up procedure.     

Experimental and theoretical study of the structure of N,N-dimethyl-4-nitroaniline derivatives as model compounds for non-linear optical organic materials

Molecular and crystal structure of a series of derivatives of N,N-dimethyl-4-nitroaniline has been studied by both X-ray diffraction method and high-level ab initio calculations. According to these data, the dimethylamino groups were found to have a trigonal-pyramidal configuration and are considerably turned with respect to the ring plane in all molecules having a substituent in the ortho-position; on the contrary, this group is planar in the meta-substituted molecules. Topological analysis of the electron density function for all molecules studied within the framework of Bader's ‘atoms in molecules’ (AIM) theory revealed that introduction of a substituent into the ortho- or meta-position of the ring results in increasing of the contribution of the resonance forms different from the quinoid one. Contribution of the latter form is predominant for the structure of N,N-dimethyl-4-nitroaniline (1). Topological analysis of the electron density distribution was used to explain a decreasing of the molecular hyperpolarisabilites of the ortho- and meta-substituted compounds as compared with those for 1.     

Aza variant of intramolecular nucleophile-catalyzed aldol lactonization (NCAL): formal synthesis of (3S,4R) and (3R,4S) 4-(hydroxymethyl)pyrrolidin-3-ol

Aza variant of intramolecular catalytic, asymmetric nucleophile-catalyzed, aldol lactonization (NCAL) reaction has been explored to synthesize β-lactone fused nitrogen heterocycles as aza sugars’ precursors by employing achiral amino acids. The utility of these bicyclic β-lactones is presented by the formal synthesis of aza sugars, (3S,4R) and (3R,4S) 4-(hydroxymethyl)pyrrolidin-3-ol.     

Reaction of an Introverted Carboxylic Acid with Carbodiimide

The reaction of carboxylic acids with carbodiimides is reviewed, and an ‘introverted’ carboxylic acid is proposed as a means of trapping reactive intermediates along the reaction pathway. The introverted acid is a cavitand with the carboxylic function directed toward the floor of the cavity. Its reaction with diisopropyl carbodiimide gives a covalent adduct that is either the elusive O-acylisourea or the commonly encountered N-acylurea.