Dienamines as Diels-Alder dienes. A novel benzannulation sequence

Diels-Alder reaction between (E)-dienamines 1, – 7 and methyl propiolate followed by elimination of Me₂NH from the intermediate cycloadducts III affords the aromatic methyl esters 8, – 14 in good yield.     

Determination of the stereochemistry of 1-substituted 3-aryltetrahydroisoquinolines by1H NMR spectroscopy

The cis-1,3-disubstituted tetrahydroisoquinolines 2 can be obtained in a highly diastereoselective fashion through Pictet-Spengler cyclization of the 1,2-bis(3,4-dimethoxyphenyl)-ethylamine with aliphatic and aromatic aldehydes under acidic conditions. However, the epimeric trans-1,3-disubstituted tetrahydroisoquinolines 3 are also isolated as minor products. The stereochemistry of the tetrahydroisoquinolines was unambiguously assigned on the basis of the¹H NMR data, and are supported by difference NOE measurements.     

Towards a multi-electrode array (MEA) system for patterned neural networks

Here we describe the development of a unique multi-electrode array (MEA) system capable of supporting patterned neural networks in vitro. The significant features of this BioMEMS system are: (1) precise and exclusive positioning of the neural cell bodies to the electrode region, (2) definition of interconnecting pathways among the neurons by using patterned self-assembled monolayers (SAMs), and (3) one-to-one stimulation and recording from precisely positioned neurons. We present for the first time the design and fabrication of an MEA chip supporting patterned neuronal networks, as well as the initial electrical recordings from two types of neurons.     

DDQ mediated regiospecific protection of primary alcohol and deprotection under neutral conditions: Application of new p-methoxy benzyl-pixyl ether as reagent of choice for nucleoside protection

A simple and efficient protocol is described for regiosepecific protection of primary hydroxyl group both in nucleosides and other molecules with p-methoxy-benzyl 2,7-dimethyl pixylether (MBDPE) in presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Furthermore, swift deprotection of 2, 7-dimethylpixyl (DMPx) is accomplished with DDQ in MeOH. Both procedures are successfully implemented on gram-scale synthesis of modified nucleosides. This protocol offers mild and neutral conditions for selective protection and deprotection of DMPx group while compatible in presence of other conventional protecting groups such as benzoyl, benzyl, THP, TBDPS and acetonide.     

Room-temperature C–H activation of the phosphino-ketone Ph2PCH2C(O)Ph leading to an iridium(III) complex with a hybrid phosphino-enolate ligand

The reaction of [Ir(cod)(μ-Cl)]₂ (cod = 1,5-cyclooctadiene) with 2 equiv of the ketophosphine Ph₂PCH₂C(O)Ph in the presence of TlPF₆ afforded the hydrido, phosphino-enolate Ir(III) complex [IrH(cod){Ph₂PCH···C(···O)Ph,κP,κO}{Ph₂PCH₂C(O)Ph,κP}]PF₆ (4), which results from the room temperature activation of a C–H bond from the PCH₂ moiety. The distorted octahedral coordination environment around the metal centre in 4 contains the cod ligand, the P atom of the monodentate ketophosphine and the P,O donor atoms of a chelating phosphino-enolate ligand acting as a 3-electron donor. The hydride ligand was located on the difference Fourier map obtained by single-crystal X-ray diffraction studies and is trans to the enolate oxygen and cis to the two, mutually cis P atoms. The reaction of this complex with NaH in THF led to the isolation of the Ir(I) complex [Ir(cod){Ph₂PCH···C(···O)Ph,κP,κO}{Ph₂PCH₂C(O)Ph,κP}] (5). The penta-coordination environment around the metal centre in 5 includes the cod ligand, one 3-electron donor P,O chelating phosphino-enolate ligand and a P-bound Ph₂PCH₂C(O)Ph ligand containing an uncoordinated ketone function. The structures of 4·CH₂Cl₂ and 5·C₇H₈ have been determined by X-ray diffraction analysis.     

cDNA cloning,expression and bioinformatical analysis of Tssk genes in tree shrews

Tree shrews are more closely related to primate animals than rodents in many aspects.In addition, they also possess several advantageous characteristics including small body size, high brain-to-body mass ratio, low cost of feeding and maintenance, short reproductive cycle and life span, which make them promising novel laboratory animals to replace more precious larger primate animals. Testis-specific serine/threonine kinase (Tssk) plays important roles in spermatogenesis and/or the regulation of sperm function. However, studies on Tssk in tree shrews have not been reported yet. In the present study, the full-length sequences of five members of the Tssk family in tree shrews were cloned and their CDS region sequences were analyzed by basic bioinformatics. The phylogenetic tree and prokaryotic protein expression system of Tssk gene of tree shrews were constructed. The mRNA expressions of Tssk genes in 11 tissues/organs from tree shrews were studied. The results showed that: 1. the length of the CDS region of tree shrew Tssk gene for Tssk1B, Tssk2, Tssk3 (variant X1 / X2), Tssk4 (variant X1 / X2) and Tssk6 is 1080bp, 1077bp, 867 / 807bp, 1014 / 984bp, 822bp, respectively, encoding 359, 358, 288/268, 337/327 and 273 amino acids, respectively; the cloned sequences of Tssk genes have been submitted to GenBank with the following accession numbers: KX091161(Tssk1B), KX091162(Tssk2), KX091163(Tssk3 variant X1)/KX091164(Tssk3 variant X2), KX091165(Tssk4variant X1)/KX091166(Tssk4variant X2), KX091160(Tssk6). 2. All tree shrew Tssk proteins distribute in cytoplasm, indicating that they are hydrophilic and non-secretory proteins, with multiple phosphorylation sites of serine and/or threonine. In addition, they are all mixed proteins with similar tertiary structures sharing a highly conserved functional domain of S_TKc (Serine/Threonine protein kinases, catalytic domain). 3.The molecular phylogenetic tree of five Tssk genes in tree shrews indicates that they are neither rodent nor primate animal, but are closely related to primate animals. 4. Five members of the Tssk recombinant proteins in tree shrews were successfully obtained using the constructed prokaryotic protein expression system. 5. Five Tssk genes are specifically expressed in the testis and/or sperm of tree shrews. Additionally, small amount of Tssk1B was expressed in several tissues other than testis and sperm. Limited mRNA levels of Tssk2 and Tssk4 were expressed in the brain, while mRNA of Tssk3 or Tssk6 could only be detected in the testis and sperm.This study will provide fundamental data on reproductive biology of tree shrews, which paves a way for further studying Tssk’s biological function in this novel model animal.     

Charge dynamics of 57Fe probe atoms in La2Li0.5Cu0.5O4

The objective of this study is to characterize the electronic state and local surrounding of ⁵⁷Fe Mössbauer probe atoms within iron-doped layered perovskite La₂Li_0.5Cu_0.5O₄ containing transition metal in unusual formal oxidation states “+3”. An approach based on the qualitative energy diagrams analysis and the calculations within the cluster configuration interaction method have been developed. It was shown that a large amount of charge is transferred via Cu-O bonds from the O: 2p bands to the Cu: 3d orbitals and the ground state is dominated by the d⁹L configuration (“Cu²⁺-O^-” state). The dominant d⁹L ground state for the (CuO₆) sublattice induces in the environment of the ⁵⁷Fe probe cations a charge transfer Fe³⁺ + O⁻(L) → Fe⁴⁺ + O²⁻, which transforms “Fe³⁺” into “Fe⁴⁺” state. The experimental spectra in the entire temperature range 77–300 K were described with the use of the stochastic two-level model based on the assumption of dynamic equilibrium between two Fe³⁺↔Fe⁴⁺ valence states related to the iron atom in the [Fe(1)O₄]^4- center. The relaxation frequencies and activation energies of the corresponding charge fluctuations were estimated based on Mössbauer data. The results are discussed assuming a temperature-induced change in the electronic state of the [CuO₄]^5- clusters in the layered perovskite.     

Pyridinethiones—III : Synthesis of dithiocines by reaction of 3-formyl-2(1H)-pyridinethione with amines. Crystal structure of the resulting 5,11-imino-5H-11H-dipyrido[2,3-b: 2',3'-f][1,5]dithiocine ring system

The reaction of 3-formyl-2(1H)-pyridinethione and alkyl or aryl primary amines gives rise to a novel imide bridged ring system. The structure 4 of this dithiocine was assigned by synthesis as well as from the spectroscopic data and the X-ray determination. The dithiocine ring was found to have the “folded” configuration. The mass spectral fragmentations of the dithiocines were investigated in detail.     

Synthesis of 3-methyl-coumarins, -thiacoumarins and -carbostyrils

Reaction of 3,6-dimethyl-4-phenyl-3,4-dihydrocoumarin5a with anhydrous aluminum chloride gave 3,6-dimethyl-coumarin (6a); likewise, 6-chloro-3-methyl-coumarin (6b) was obtained from5b. Substituted 3-methyl-thiacoumarins (8a,b and 3-methyl-carbostyrils (10a-e) were prepared from the reactions of the respectivea-methyl-cinnamoyl derivatives (7a,b and (9a-e), of thiophenols and anilines.     

Two new xenicin diterpenoids from the octocoral anthelia edmondsoni

From the soft coral Antheliaedmondsoni two new diterpenoids, waixenicin-A (1) and -B (2) have been Isolated. Their structures were elucidated by¹H and¹³C NMR analysis and the relative stereochemistry was determined by x-ray diffraction of crystalline waixenicin-B (2).     

Asymmetric synthesis of anthracyclinones using chiral acetal: synthesis of a new chiral AB-synthon, ()-2-bromo-6-ethynyl-6-hydroxy-5, 6, 7, 8-tetrahydro-1, 4-naphthoquinone,and its application for ()-7-deoxydaunomycinone

A synthesis of a new chiral AB-synthon (4) for preparing the optically active anthracyclinones was attained through a stereospecific nucleophilic addition of trimethylsilylethynylmagnesium chloride to the chiral 2-tetralone-1-acetal (2). Synthesis of ()-7-deoxydaunomycinone (1c) was achieved by a regiospecific cycloaddition of4 to 4-acetoxy-8-methoxyhomophthalic anhydride (5).     

2-benzopyrylium salts. XXXVII. Oxygen analogs of reissert compounds : molecular structure and reactions with sodium hydroxide

The weak intensity of the CN stretching band in IR spectra for 1-cyanoiso chromenes is obviously determined by the steric position of the CN group in the molecule, as it was established by X-ray structural analysis for the cyanide addition product 2d of 1-isopropyl-3-methyl-2-benzopyrylium salts. Depending on the other substituent in position 1, 1-cyanoisochromenes in aqueous solutions of sodium hydroxide eliminate hydrogen cyanide 2a, b, e, undergo inter-3a, b or intra-mlecular 2c, d recyclisation, or hydrolysis of the cyano group in 2f ; reaction products include α-naphthols 7c, e, β-naphthol 7d, acylchrysenes 5a, b, or the iso chromene-amide 11f , a stable 1-alkylideneisochromene 3e was obtained, and the intermediacy of 3-hydroxy-1-alkylideneiso chromenes was proved by their isolation in the cases of 10c, d     

Highly stereoselective reduction of chiral α-keto-β, γ-unsaturated acetals: Synthesis of both epimeric allyl alcohols by proper choice of additive

Highly stereoselective reduction of chiral α-keto-β, γ-unsaturated acetals (1a-3a) into each two epimeric optically active allyl alcohols (1b-3b and1c-3c) was attained by LiAlH₄ using additive (LiBr, MgBr₂).     

Synthesis of natural triisopentenylated flavanone, euchrenone a2

Euchrenone a₂ (7) isolated from the roots ofEuchresta japonica has been synthesised from 3-prenylphloroacetophenone (1) by other workers. We carried out its cyclodehydrogenation with dichloro dicyano quinone (DDQ) to obtain 6-acetyl-5,7-dihydroxy-2,2-dimethylchromene (2) which was ethoxymethylated in the 7-position to give 6-acetyl-7-ethoxymethoxy-5-hydroxychromene (3). Chalcone condensation of3 and 4-ethoxymethoxy-3-C-prenylbenzaldehyde (4) gave 4,6′-bisethoxymethoxy-2′-hydroxy-6″, 6″-dimethyl-3-C-prenylpyrano (2″, 3″–4,3) chalcone (5) which cyclised with methanolic sodium acetate to give protected 5,4′-bisethoxymethoxy-6″, 6″-dimethyl-3′-C-prenylpyrano (2″, 3″–7,8) flavanone (6). Deprotection of6 with 4% methanolic HCl yielded (7) with melting point and spectral data identical to that of the natural compound.     

Determination of stereostructure of naturally occurring α, β-unsaturated δ-lactone derivatives through a stereoselective synthesis

The stereostructures of (Z)-tarchonanthuslactone (2) and the δ-lactone of (Z)-5, 7, 9, 11-tetrahydroxyhexacos-2-enoic acid (3) were established as9 and27 by the stereoselective syntheses of authentic9 and26 (triacetate of3), respectively.     

Saturated heterocycles 115: Cycloaddition of nitrilimine and nitrile oxide to norbornane- and norbornene-fused dihydro-1,3-oxazines

By cycloaddition of nitrilimine and nitrile oxide to diexo and diendo norbornane- and norbornene-fused structural isomeric dihydro-1,3-oxazlnes (1-3), tetracyclic 1,3-oxazino-1, 2,4-trlazolines (7-9) and 1,2,4-oxadiazolines (10-12) were obtained. With norbornehe dipolarophiles, which contain a C=N and a C=C bond, the cycloaddition takes place at the olefinic bond and the diexo compound 4 yields 13 regioselectively, whereas the diendo isomer 5 gives an Isomeric mixture of isoxazolines 14 and 15. From the diexo derivative 6, however, a bis-adduct 16 is formed. The stereostructures of the adducts have been elucidated by NMR spectroscopy.     

Formation of a bis-lactone from 3-O-acetyl-deoxycholic acid

By the action of dichloroethyl phosphate upon 3α-acetoxy-12α-hydroxy-5β-cholanic acid (1) in methylene chloride, unexpectedly, a bis-lactone2 was formed. Sodium methoxide catalyzed deacetylation of2 afforded 16-membered deoxycholic acid 24, 12'α: 24′, 12α-bis-lactone (3) whose structure was determined by an x-ray structural analysis.     

A General Method for Stepwise Elongation of the (1→5)-α-D-Arabinofuranan Chain

Condensation reaction of 3,5-di-O-benzoyl-1,2-O-(1-cyanoben-zylidene)-β-D-arabinofuranose (2) with benzyl and allyl 2,3-di-O-benzoyl-5-O-triphenylmethyl-α-L-arabinofuranosides (5a and 5b) in methylene chloride in the presence of triphenylcarbenium tetrafluoroborate as catalyst under high vacuum gave α-(1→5)-linked dimeric D-arabinofuranoside derivatives (6a and 6b). One of the dimeric compounds (6a) was debenzoylated, triphenylmethylated, and rebenzoylated to give a dimeric homolog of 5a (8). Similarly for the preparation of 6a, 8 was condensed with 2 to provide an α-(1→5)-linked trimeric D-arabinofuranoside derivative (9). Further elongation of the glycoside chain might be possible in the same way.     

Synthesis of A-B-C-ring segment of thyrsiferol construction of a strained tetrahydropyran ring existent as a boat form

Tricyclic bromoether17, which contained twenty of thirty carbons of thyrsiferol (1d), was synthesized in optically active form starting from trivial compounds2 and3.     

New synthesis of steroidal tetrahydrooxazin-2-ones

In the DMSO/NaHCO₃ system, 16α-aminomethyl-, 16α-benzylaminomethyl- and substituted benzylaminomethyl-3-methoxy-17β-tosyloxyestra-1,3, 5(10)-triene (3, 5a-k) do not undergo oxidation, but form a tetrahydrooxa-zin-2-one ring (7, 8a-k) via neighboring group participation. Under similar conditions, 16β-aminomethyl-3-methoxy-17β-tosylestra-1,3,5(10)-triene (4) decomposes into 16-methylene-3-methoxyestra-l,3,5(10)-trien-17-one (12).