Titanium-mediated syntheses of cyclopropylamines

The transformations of N,N-dialkylcarboxamides and nitriles with 1,2-dicarbanionic organometallics in situ generated from organomagnesium (Grignard) as well as organozinc reagents in the presence of stoichiometric or substoichiometric (semi-catalytic) quantities of a titanium alkoxide derivative of type XTi(OR)₃ with X=OR, Cl, Me and OR=OiPr, OEt are described. The key step in the transformation of a monocarbanionic into a 1,2-dicarbanionic organotitanium species is a disproportionation of a dialkyltitanium intermediate to form an alkane and a titanium alkene complex which has the reactivity of a titanacyclopropane derivative. The latter are able to undergo insertion of the carbonyl group of an N,N-dialkylcarboxamide or a cyano group to furnish, after ring contraction and hydrolysis, dialkylcyclopropylamines or cyclopropylamines, respectively. The titanium alkene complexes can also undergo ligand exchange with alkenes to afford new titanacyclopropanes, which subsequently react as 1,2-dicarbanionic equivalents. In many cases, these titanium-mediated formations of a wide range of synthetically and/or pharmacologically important cyclopropylamines proceed in good to very good yields (from 20% to 98% for dialkylcyclopropylamines from N,N-dialkylcarboxamides and from 27% to 73% for primary cyclopropylamines from nitriles) and with high chemo- and stereoselectivity. These circumstances in conjunction with the simplicity of the experimental handling and inexpensiveness of the reagents favor these reactions for an ever increasing range of applications in organic synthesis.     

Two-photon ionization of an inner shell electron of the Cl atom

We have calculated, using second order perturbation theory, the two photon ionization cross section of a K-shell electron of chlorine forE=1.6 keV incident photons. Two classes of intermediate states must be considered, those in which a 1s electron moves to an emptyp-orbital, and those in which an electron from an occupiedp-orbital moves into the continuum. The first class of intermediate states is followed by the ejection of ap-electron into the continuum. The second class of intermediate states is followed by the transfer of a 1s electron into an emptyp-state. The largest contribution comes from 3p →d-continuum followed by 1s → 3p transition. Our result is σ⁽²⁾/I=2.06×10⁴¹ cm⁴/W where σ⁽²⁾ is the two photon ionization cross-section andI is the light intensity.     

Synthesis of chiral ortho-thio-substituted phenyl phosphonodiamidates via a P-S to P-C rearrangement

The ortho-lithiation of a phenyl phosphorodiamidothioate derived from an enantiopure C₂-symmetric diamine is studied. It is shown that the migration of the diaminophosphoryl group from sulfur to carbon, leading to an ortho-sulfanylated phenyl phosphonodiamidate, only occurs in the presence of an alkylating agent or a Lewis acid as BF₃·Et₂O. The influence of the chiral diaminophosphoryl group on the stereoselectivity of the oxidation of the ortho-sulfanyl or alkylsulfanyl group is also examined.     

Synthesis of the all-cis-trimethyldecalin fragment of unusual terpenes by radical-mediated protonolysis of an alkylboron derivative

The synthesis of an enantiopure building-block with a contiguous all-cis-trimethyldecalin motif embedded in unusual terpenes is described. Starting from the Wieland–Miescher ketone, the key step is a one-pot hydroboration of an exocyclic methylene double bond promoted by disiamylborane and radical-mediated protonolysis of the corresponding alkylborane using 4-tert-butylcatechol.     

Evolving trends in the dereplication of natural product extracts. 3: further lasiodiplodins from Lasiodiplodia theobromae, an endophyte from Mapania kurzii

Two further lasiodiplodins, (3R,4R)-4-hydroxy-de-O-methyl-lasiodiplodin and (E)-9-etheno-de-O-methyl-lasiodiplodin, together with three known lasiodiplodins from a cytotoxic extract obtained from a culture of Lasiodiplodia theobromae, an endophyte from the root tissues of Mapania kurzii (Cyperaceae) from the Malaysian rain forest, were characterized on microgram scale.     

Isolation, synthesis and photochemical properties of almazolone, a new indole alkaloid from a red alga of Senegal

An indole alkaloid bearing an oxazolone ring, christened almazolone, has been isolated from a new collection of Haraldiophyllum sp. from Dakar (Senegal), as an 88:12 mixture of (Z)/(E) stereoisomers. The relative ratio could be modified under controlled photochemical and thermal processes. The product (Z)-3-indolyl-2-(phenyl-propionylamino)-acrylic acid obtained by oxazolone ring opening has also been observed. Its formation has been confirmed by alkaline hydrolysis of (Z)-almazolone available from synthesis, where condensation of indole-3-carboxaldehyde with (3-phenylpropionylamino)-acetic acid represents the key step.     

Highly diastereo- and enantioselective reactions of enecarbamates with an aldehyde

Catalytic asymmetric addition reactions of enecarbamates with ethyl glyoxylate have been developed using CuClO₄·4CH₃CN and a diimine ligand as the catalyst. Highly diastereo- and enantioselective addition reactions of α-mono-substituted enecarbamates have been also achieved. These reactions afforded the corresponding adducts with high selectivity; that is, syn adducts from Z-enecarbamates and anti adducts from E-enecarbamates. The proposed reaction mechanism is an aza-ene type pathway, where the proton of an enecarbamate's N-H group plays an important role, not only for accelerating the reaction but also for providing a transition state suitable for the highly selective chiral induction.     

Synthesis of the benzo-β-carboline isoneocryptolepine: the missing indoloquinoline isomer in the alkaloid series cryptolepine, neocryptolepine and isocryptolepine

7H-Indolo[2,3-c]quinoline has been synthesized in two steps via a new approach starting from commercially available 3-bromoquinoline and 2-bromoaniline. The new methodology consists of two consecutive palladium-catalyzed reactions: a selective Buchwald/Hartwig amination followed by an intramolecular Heck-type reaction. Alternatively, the same skeleton has also been prepared via the combination of a Suzuki arylation with an intramolecular nitrene insertion starting from 4-chloroquinoline and {2-[(2,2-dimethylpropanoyl)amino]phenyl}boronic acid. Selective methylation of 7H-indolo[2,3-c]quinoline yielded 5-methyl-5H-indolo[2,3-c]quinoline (Isoneocryptolepine) which is an interesting new lead compound in the search for new antiplasmodial drugs.     

Synthetic route towards (5R,2′S,5′S,6′S)-ribosyl-diazepanone,an analogue core of the liposidomycins

The synthesis of (5R,2′S,5′S,6′S)-ribosyl-diazepanone, an analogue core of liposidomycins is described. The core ribosyl seven-membered heterocycle of nucleoside antibiotic liposidomycins was formed by reductive amination of an α-ribosylamino ester derived from d-ribose, and an amino aldehyde derived from methyl 4-triisopropylsilyloxy-3-oxobutanoate, followed by a peptidic coupling reaction.     

N-Dealkylation of Amines

N-dealkylation, the removal of an N-alkyl group from an amine, is an important chemical transformation which provides routes for the synthesis of a wide range of pharmaceuticals, agrochemicals, bulk and fine chemicals. N-dealkylation of amines is also an important in vivo metabolic pathway in the metabolism of xenobiotics. Identification and synthesis of drug metabolites such as N-dealkylated metabolites are necessary throughout all phases of drug development studies. In this review, different approaches for the N-dealkylation of amines including chemical, catalytic, electrochemical, photochemical and enzymatic methods will be discussed.     

Electrochemical preparation of self-doped poly(o-aminobenzenesulfonic acid-co-aniline) microflowers

Self-doped poly(o-aminobenzenesulfonic-acid-co-aniline) (abbr. p(oASA-co-Ani)) nanoflowers were prepared by an electrochemical preparation without any other supporting electrolytes. The images of scanning electron microscope show that the nanoflowers are uniform. In addition, the results obtained from the cyclic voltammetry indicate that it exhibits a remarkable electroactivity at an extended pH range from 3 to 13.5.     

N-Glycomics of Cerebrospinal Fluid: Method Comparison

Cerebrospinal fluid (CSF) contains valuable biological and neurological information. However, its glycomics analysis is hampered due to the low amount of protein in the biofluid, as has been demonstrated by other glycomics studies using a substantial amount of CSF. In this work, we investigated different N-glycan sample preparation approaches to develop a more sensitive method. These methods, one with an increased amount of buffer solution during the N-glycan release step with a lower amount of sample volume and the other with Filter-Aided N-Glycan Separation (FANGS), were compared with recent work to demonstrate their effectiveness. It was demonstrated that an increased amount of buffer solution showed higher intensity in comparison to the previously published method and FANGS. This suggested that digestion efficiency during the N-glycan release step was not in an optimal condition from the previously published method, and that there is a substantial loss of sample with FANGS when preparing N-glycans from CSF.     

Tellurium in organic synthesis: the enantioselective synthesis of the pheromone blend components of Mayetiola destructor,Drosophila mulleri and Contarinia pisi

The components of the pheromone blend of Mayetiola destructor, Drosophila mulleri, and Contarinia pisi were synthesized in high enantiomeric excess (99% ee) from a common enantiopure dianion prepared from an enantiopure hydroxytelluride.     

Structure and absolute configuration of 3-alkylpiperidine alkaloids from an Indonesian sponge of the genus Halichondria

Chemical analysis of an Indonesian sponge sample has provided three new 3-alkylpiperidine alkaloids, tetradehydrohaliclonacyclamine A, its mono-N-oxide derivative, and a 2-epi isomer. The absolute structure of tetradehydrohaliclonacyclamine A has been established by X-ray crystallography from anomalous dispersion effects using Cu radiation, which determined that the absolute configuration is 2S, 3S, 7S, 9S while an HPLC study revealed that the alkaloid is enantiomerically pure.     

N-alkylation of nitriles(1)—II. Synthesis polymerization and quaternization of N-substituted acrylamidines. A new class of acrylic monomers16)

N-Substituted acrylamidines, a new class of acrylic monomers, have been prepared from acrylonitrile, an alkyl halide, a Lewis acid and an amine. The synthesis involves the aminolysis of an N-alkylacrylonitrilium salt with an aliphatic or an aromatic amine. Following this general scheme, 4 examples of N-substituted acrylamidines have been already obtained in 30–50 per cent overall yield based on the starting nitrile. Two of them have been polymerized with azobisisobutyronitrile as initiator. By the action of dimethylsulphate, a polyacrylamidinium salt (a new type of polyelectrolyte) has been prepared.     

Evaluation of the thermochemical changes in agricultural by-products and in the carbon adsorbents obtained from them

The thermochemical decomposition of waste products from a coconut (Cocos nucifera L.), a nut (Juglans regia L.) an apricot (Armeniaca vulgaris L.), an almond (Amygdalus communis L.var amara DC.), a grape (Vitis vinifera L.) and a cherry (Prunus avium L.), as raw materials for producing carbon adsorbents, was investigated by DTA and TG. The thermo-oxidative and decomposition processes resulting in increased number of oxygen-containing functional groups of phenolic and carbonyl type are responsible for the high adsorption capacities of the carbon adsorbents. The thermochemical changes in adsorbents based on agricultural wastes are similar to those in commercial activated carbons. The adsorbents derived from apricot stones have the highest overall thermal stability.     

Switched enantiopreference of Humicola lipase for 2-phenoxyalkanoic acid ester homologs can be rationalized by different substrate binding modes

Humicola lanuginosa lipase was used for enantioselective hydrolyses of a series of homologous 2-phenoxyalkanoic acid ethyl esters. The enantioselectivity (E-value) of the enzyme changed from an (R)-enantiomer preference for the smallest substrate, 2-phenoxypropanoic acid ester, to an (S)-enantiomer preference for the homologous esters with longer acyl moieties. The E-values span the range from E=13 (R) to E=56 (S). A molecular modeling study identified two different substrate-binding modes for each enantiomer. We found that the enantiomers favored different modes. This discovery provided a model that offered a rational explanation for the observed switch in enantioselectivity.     

Metabolic Engineering of Escherichia coli for Production of 2-phenylethanol from Renewable Glucose

2-Phenylethanol (2-PE) is an important aromatic alcohol with a rose-like odor and has wide applications. The present work aims to construct a synthetic pathway for 2-PE synthesis from glucose in Escherichia coli. First, the genes adh1 (encoding alcohol dehydrogenase) and kdc (encoding phenylpyruvate decarboxylase) from Saccharomyces cerevisiae S288c and Pichia pastoris GS115 were investigated in E. coli, respectively, and single overexpression of adh1 or kdc significantly increased 2-PE accumulation. When co-overexpressing adh1 and kdc, 2-PE was increased up to 130 from 57 mg/L. Furthermore, by optimizing coordinated expression of the four committed genes aroF, pheA, adh1 and kdc, 2-PE was improved to 285 mg/L which was the highest production of 2-PE by the recombinant E. coli system. In addition, our results also demonstrated that the tyrB gene, which encodes aromatic-amino-acid transaminase, plays an important role on 2-PE synthesis.     

The effect of inert additives on the explosive mechanochemical synthesis of some metal chalcogenides

The effect of different inert additives on the mechanochemical synthesis of SnS was studied. A transition from explosive to nonexplosive mechanochemical reaction was observed. It was shown that this change takes place only when a critical volume x_c is occupied by inert material. The critical volume for a transition from an explosive to nonexplosive mechanochemical synthesis were determined for the chalcogenides of Zn, Cd, and Sn. The x_c values obtained are discussed. On the basis of the new data concerning the critical dimensions r_c of the exploding mechanical aggregates and the percolation phenomena, a mechanism for the transition from an explosive to nonexplosive mechanochemical synthesis is suggested.     

Total synthesis of (±) maculalactone A, maculalactone B and maculalactone C and the determination of the absolute configuration of natural (+) maculalactone A by asymmetric synthesis

Maculalactones A, B and C from the marine cyanobacterium Kyrtuthrix maculans are amongst the only compounds based on the tribenzylbutyrolactone skeleton known in nature and (+) maculalactone A from the natural source possesses significant biological activity against various marine herbivores and marine settlers. We now report a concise synthesis of racemic maculalactone A in five steps from inexpensive starting materials. Maculalactones B and C were synthesized by a minor modification to this procedure, and the synthetic design also permitted an asymmetric synthesis of maculalactone A to be achieved in around 85% ee. The (+) and (−) enantiomers of maculalactone A were assigned, respectively, to the S and R configurations on the basis of the chiral selectivity expected for catecholborane reduction of an unsymmetrical ketone in the presence of Corey's oxazoborolidine catalyst. Surprisingly, it appeared that natural (+) maculalactone A was biosynthesized in K. maculans in a partially racemic form, comprising ca. 90-95% of the (S) enantiomer and 5-10% of its (R) enantiomer. Coincidentally therefore, the percentage enantiomeric excess of the product obtained from asymmetric synthesis almost exactly matched that found in nature.