Synthesis and structure of new β-functionalized gem-bromonitroethenes — 2-arylsulfanyl- and 2-aryloxy-3-bromo-3-nitroacrylates

Alkyl 2,3-dibromo-3-nitroacrylates react with arylthiols and phenols to give earlier unknown representatives of β-functionalized gem-bromonitroethenes, namely, 2-arylsulfanyl- and 2-aryloxy-3-bromo-3-nitroacrylates; their structure was characterized by IR, UV, and NMR (¹H, ¹³C{¹H}, HMQC, HMBC) spectroscopy. X-ray diffraction analysis showed that methyl 3-bromo-2-(4-chlorophenylsulfanyl)-3-nitroacrylate has a Z-configuration; the sulfanylbromonitrovinyl fragment in its molecule is relatively coplanar, while the ester group is almost perpendicular to the plane of the C-C double bond.

     

Synthesis of β3-amino acid and peptides from D-ribose

Synthesis of new β³-amino acid, peptides and conformational analysis are reported from d-ribose, using Wittig olefination and Aza-Michael addition.     

Synthesis of β-formyl-2,5-dialkoxytetrahydrofurans and their reaction with 3-amino-1,2,4-triazole

New -formyl-2,5-dialkoxytetrahydrofurans were synthesized by hydroformylation of the corresponding 2,5-dihydrofurans. The aldehydes obtained react with 3-amino-1,2,4-triazole to give 6-(2-oxopropyl)-1,2,4-triazolo[1,5-a]pyrimidines.Translated fromIzyestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1997–2001, November, 1994.     

ZrCl4-Catalyzed Synthesis of β-Aminosulfides from Aziridines and Thiols

A simple and efficient synthesis of β-aminosulfides has been introduced by ring opening of aziridine rings with aromatic thiols in the presence of zirconium(IV) chloride under solvent-free conditions at room temperature.     

New protocols for the synthesis of 3,4-annulated and 4-substituted quinolines from β-bromo-α,β-unsaturated aldehydes and 1-bromo-2-nitrobenzene or 2-bromoacetanilide

The palladium[0]-mediated Ullmann cross-coupling of readily available β-bromo-α,β-unsaturated aldehydes of the general form 2 with 1-bromo-2-nitrobenzene (3, X = Br) delivers products, 4, that undergo reductive cyclization to novel quinolines (5) upon exposure to indium in aqueous ammonium chloride or to Raney-nickel in the presence of dihydrogen. Analogous cross-coupling of 2-bromoacetanilide (6) with 2 affords products of type 7 that undergo in situ and K₂CO₃-mediated cyclization to give the same types of quinolines (5).     

Synthesis of 2′,3′-dideoxynucleosides from 5-alkoxymethyluracils

Summary A modified synthesis of protected 2,3-dideoxyribose5 starting fromL-glutamic acid (1) is described. Reaction of5 with silylated 5-hydroxymethyluracil7 a and 5-alkoxymethyluracils7 b–e in the presence of trimethylsilyl triflate afforded an anomeric mixture of 2,3-dideoxyuridine derivatives8 a–e and9 a–e. Deprotection with methanolic ammonia and separation by chromatography gave the corresponding nucleosides10 a–e and11 a–e. Treatment of9 b–e with tri(1H-1,2,4-triazol-1-yl)phosphine oxide and subsequent reaction of12 b–e with ammonia in dioxane afforded the cytosine derivatives13 b–e which on treatment with methanolic ammonia gave the corresponding 2,3-dideoxycytidine derivatives14 b–e and15 b–e. In contrast with the parent compounds, these alkoxymethyl derivatives had no appreciable activity against human immunodeficiency virus (HIV-1).

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Synthese von 2,3-Dideoxynucleosiden aus 5-Alkoxymethyluracilen

Zusammenfassung Ausgehend vonL-Glutaminsäure (1) wird eine modifizierte Synthese von geschützter 2,3-Dideoxyribose (5) beschrieben. Reaktion von5 mit silyliertem 5-Alkoxymethyluracilen7 b–e in Gegenwart von Trimethylsilyltriflat ergab anomere Mischungen der 2,3-Dideoxyuridinderivate8 a–e und9 a–e. Abspaltung der Schutzgruppe mit methanolischen Ammoniak und chromatographische Trennung ergab die entsprechenden Nucleoside10 a–e und11 a–e. Behandlung von9 b–e mit Tri(1H-1,2,4-triazol-1-yl)phosphinoxid und nachfolgende Reaktion von12 b–e mit Ammoniak in Dioxan ergab die Cytosinderivate13 b–e, welche nach Behandlung mit methanolischem Ammoniak die entsprechenden 2,3-Dideoxycytidinderivate14 b–e und15 b–e ergaben. Im Gegensatz zur Stammverbindung hatten diese Alkoxymethylderivate keine nennenswerte Wirksamkeit gegen den menschlichen Immunschwächevirus (HIV-1).

     

Synthesis of 4″O,5O-bis(2-amino-2-thioxoacetyl)ivermectin derivatives

Reaction of 4″O,5O-bis(chloroacetyl)ivermectin with amines in the presence of sulfur provided the corresponding bis(2-amino-2-thioxoacetyl) derivatives that are potential antiparasitics.

     

Synthesis and antiangiogenic activities of 5-amino-1,3-dihydro-1, 3-dioxo-2H-isoindole-2-propanoic acid derivatives

Based on the structure-activity relationships and antiangiogenic mechanism of RGD-containing peptides,a series of 5-amino- 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized.The structures were characterized by ~1H NMR,MS and elementary analysis.There ability to inhibit angiogenesis were evaluated by chick embryo chorioallantoic membrane assay at 10~(-5) mol/L.Compounds 7a and 7b displayed obvious antiangiogenic activity.     

Synthesis of 5 β-Chloro-4α-methoxysantonin Oxime

The newderivative 5-chloro-4-methoxysantonin oximewasprepared from5-chloro-4-methoxysantonin by reaction with hydroxylamine hydrochloride in the presence of pyridine. The structure was established by IR, UV, and PMR spectroscopies.     

Synthesis of 2-hydroxy-5,6-diarylnicotinonitriles and 2-chloro-5,6-diarylnicotinonitriles from β-chloroenones

Vilsmeier–Haack reaction of β-ketoaldehydes leads to the formation of β-chloroenones and these chloroenones on treatment with malononitrile afford 2-hydroxy-5,6-diarylnicotinonitriles. But a one-pot reaction of β-ketoaldehydes with Vilsmeier–Haack reagent and malononitrile or cyanoacetamide results in the formation of 2-chloro-5,6-diarylnicotinonitriles in good yields.     

Synthesis of macrocyclic systems from 4,4′-diamino-3,3′-bi-1,2,5-oxadiazole and 3(4)-amino-4(3)-(4-amino-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazole 2-oxides

Oxidative cyclocondensation of 4,4′-diamino-3,3′-bi-1,2,5-oxadiazole and isomeric 3(4)-amino-4(3)-(4-amino-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazole 2-oxides under the action of dibro-moisocyanurate gave 12- and 18-membered macrocyclic systems containing two or three bifurazanyl or furazanylfuroxanyl moieties linked by azo bridges. The latter were oxidized into azoxy groups with Caro’s acid in 20% oleum. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 631–638, March, 2008.     

Synthesis of the β2-Agonist Tulobuterol and Its Metabolite 4-Hydroxytulobuterol

Russian Journal of Organic Chemistry - Alternative methods have been developed for the synthesis of the β2-agonist tulobuterol and its metabolite 4-hydroxytulobuterol with a similar activity....     

Synthesis and Crystal Structure of 1-（2,6-Dichloro-4-nitrophenyl）-5-amino-4-cyanopyrazole

The crystal structure of 1-（2,6-dichloro-4-nitrophenyl）-5-amino-4-cyanopyrazole （C10H10Cl2N5O2, Mr = 298.09） has been determined by single-crystal X-ray diffraction. It crystallizes in the triclinic system, space group P1^- with a = 8.1258（10）, b = 8.6460（10）, c = 10.0214（12） A, α = 68.986（2）, β = 71.598（2）, γ = 85.181（2）°, V = 623.26（13） A3, Z = 2, Dc = 1.588 g/cm^3,μ = 0.525 mm^-1, F（000） = 300, R = 0.0613 and wR = 0.1524 for 1890 observed reflections, and the extinction coefficient = 0.010（5）. The crystal structure is stabilized by N-H...N hydrogen bonds.     

Synthesis and Characterization of Manganese Tetrafluoride β-MnF4

The crystal structure of β-MnF₄ has finally been elucidated. It crystallizes in the non-centrosymmetric space group R3c, no. 161, hR360, with the lattice parameters a = 19.390(3), c = 12.940(3) Å, V = 4213.3(14) ų, Z = 72, T = 100 K. It is a 4a × 4a superstructure of the VF₃ (FeF₃) structure type. The Mn atoms are coordinated octahedron-like by F atoms, of which two are bound terminal, while the other act as μ-bridging F atoms to other Mn atoms forming a three-dimensional infinite network structure which can be described by the Niggli formula ³_∞[MnF_4/2F_2/1]. Voids on the metal sites, which are occupied in the VF₃ structure, are grouped together in the shape of a “star” with approximate D_3h symmetry. We prepared β-MnF₄ photochemically according to the literature and obtained a phase-pure powder as evidenced by X-ray diffraction at room temperature. The lattice parameters are a = 19.566(3), c = 12.984(2) Å, V = 4304(1) ų. IR and Raman spectra recorded on the powder show that β-MnF₄ has also been obtained free of moisture, HF, and O₂⁺ containing compounds, however MnF₃ is likely present as a magnetic impurity. We observe thermal decomposition of MnF₄ to MnF₂ and not MnF₃.     

Synthesis of β-Lactams from Acids and Imines Using Thiocarbonyldiimidazole

Thiocarbonyldiimidazole has been found to be an efficient acid activator for the synthesis of β-lactams by ketene-imine cycloaddition at room temperature. The experimental procedure is simple and results in excellent yields of the products. All products were characterized by spectral data and elemental analyses.     

Synthesis and Evaluation of 2-Deoxy-2-amino-β-cellobiosides as Cellulase Inhibitors

The cellulase mixture of Hypocrea jecorina (formerly Trichoderma reesei) contains a variety of exo- and endoglucanases that belong to different structural families. As such, these enzymes form an interesting model system to study the enzyme-ligand interactions in glycoside hydrolases. The nucleophilic carboxylate of retaining β-glycosidases is believed to form a hydrogen bond with the 2-hydroxyl group of their substrate. Consequently, replacing this hydroxyl group with an amino group should result in a stronger electrostatic interaction and thus an increased affinity for the ligand. In this study, several modified cellobiosides were synthesized and evaluated as cellulase inhibitors. The introduction of an amino group was found to have an unpredictable effect on the inhibitory power of the ligands. However, the enzymes display a very high affinity for the corresponding 2-azido compounds, precursors in the synthetic route. The new ligand m-iodobenzyl 2-deoxy-2-azido-β-cellobioside even is the strongest inhibitor of cellobiohydrolase I known to date (K_I = 1 μM).     

Synthesis of γ-halogenated and long-chain β-hydroxy-α-amino acids and 2-amino-1,3-diols using threonine aldolases

The l- and d-threonine aldolase catalyzed formation of γ-halogenated and long-chain l- and d-3-alkylserine-derivatives 1-12, respectively, was shown starting from glycine and halogenated C₂- or C₄-C₁₂ aldehydes. lTA from Pseudomonas putida accepted all tested aldehydes with strongly varying diastereoselectivity (de up to 93%). Only aldehydes smaller than decanal were converted by dTA from Alcaligenes xylosoxidans with good selectivities (de up to 73%). Utilizing isobutanal enantio- and diastereopure d-syn-2-amino-3-hydroxy-4-methylpentanoic acid was obtained (ee>99%, de>95%), which was converted to the corresponding 2-amino-1,3-diol.     

Synthesis and reactions of 4-amino-3-carbethoxy-1,2-dihydrospiro(naphthalene-2,1′-cyclopentane)

Addition of benzylmagnesium chloride to cyclopentylidenecyanoacetic ester gives 1-benzyl-1-(cyanocarbethoxymethyl)cyclopentane and this can be cyclized to 4-amino-3-carbethoxy-1,2-dihydrospiro-(naphthalene-2,1-cyclopentane). Acylation of the obtained aminoester with carboxylic acid chlorides produces the corresponding amides (which can react with an excess of benzoyl chloride). It can also react with orthoformic ester. In both cases the product can then react with hydrazine hydrate. Treatment of the same aminoester with caprolactam gives a tetrahydrospiro(benzo[h]quinazoline-5,1-cyclopentane) derivative.A. L. Mndzhoyan Institute of Fine Organic Chemistry, National Academy of Sciences of the Republic of Armenia, Yerevan 375014. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 820–823, June, 1998.     

Synthesis of 5-acetyloxazoles and 1,2-diketones from β-alkoxy-β-ketoenamides and their subsequent transformations

Lithiated alkoxyallenes, nitriles, and carboxylic acids have been employed as precursors in a three-component reaction leading to highly substituted β-alkoxy-β-ketoenamides. Upon treatment with trifluoroacetic acid, these enamides could be easily cyclized to 5-acetyloxazole derivatives. The synthesis is very flexible with respect to the substitution pattern at C-2 and C-4 of the oxazole core. A mechanistic suggestion for the oxazole formation is presented on the basis of (18)O-labeled compounds and their mass spectrometric analysis. In several cases, 1,2-diketones are formed as side products or even as major components. The acetyl moiety at C-5 of the oxazole derivatives can efficiently be converted into alkenyl or alkynyl moieties, which allows a multitude of subsequent reactions. Condensation reactions of the acetyl group provided the expected oxime or hydrazone. By applying a Fischer reaction, the phenylhydrazone could be transferred into an indole, which emphasizes the potential of 5-acetyloxazoles for the preparation of highly substituted (poly)heterocyclic systems. The alkynyl group at C-2 is prone to addition reactions, providing an enamine with interesting photophysical properties. Sonogashira couplings were performed with 5-alkynyl-substituted oxazoles, furnishing the expected aryl-substituted products. This alkynyl unit was employed for the preparation of a new, star-shaped trisoxazole derivative. The ability of this multivalent compound to form self-assembled monolayers between the basal plane of highly oriented pyrolytic graphite and 1-phenyloctane was demonstrated by scanning tunneling microscopy (STM). The star-shaped compound seems to prefer the C(3)-symmetric arrangement in this two-dimensional crystal. Two 1,2-diketones were smoothly converted into functionalized quinoxaline derivatives.