Synthesis of some mono- and bis-spiro-β-lactams of benzylisatin

Some new mono- and bis-spiro-β-lactams of benzylisatin were prepared by Staudinger’s ketene-imine [2+2] cycloaddition reaction. The cycloadducts were characterized by spectral data including ¹H NMR, ¹³C NMR, IR and mass spectra. The configuration of benzylisatin and one of mono-spiro-β-lactams (5a) was established by X-ray crystal analysis.     

Synthesis of novel β-lactams bearing an anthraquinone moiety,and evaluation of their antimalarial activities

A novel series of β-lactams bearing an anthraquinone moiety have been synthesized from imines derived from anthraquinone-2-carbaldehyde and ketenes by a [2+2] cycloaddition reaction. The cycloadducts were fully characterized and evaluated for their antimalarial activities against Plasmodium falciparum K14 resistant strain and showed moderate to excellent EC₅₀ values varying from 9 to 50 μM.     

α-Spiro endoperoxides: synthesis and evaluation of their antimalarial activities

Endoperoxides belonging to the G-factor family, containing a spiroalkane moiety in the α position to the O-O bond, have been synthesized via an autoxidation reaction on the corresponding dienol precursors. Methylated derivatives in the peroxyhemiketal position have also been prepared. The in vitro antimalarial activities are reported. Fe(II)-induced reduction on endoperoxides 8 and 9 have been studied.     

Synthesis of 6,8-dichloroquinolones utilizing new method and evaluation of their antibacterial activities

Several 6,8-dichloroquinolone analogues were synthesized from the key intermediate compound of 2,3,4,5-tetrachlorobenzene carbonyl chloride,which was obtained from the starting material of tetrachlorophthalic anhydride.Their in vitro antibacterial activities were evaluated.As a result of this study,compounds 21c and 21d were twofold more potent than ciprofloxacin (CPFX) and norfloxacin (NFLX) against Staphylococcus aureus-9,and with the same potent as CPFX and NFLX while against Escherichia coli-2,but were less potent than references in against Pseudomonas aeruginosa-17.     

Synthesis of chiral spiropyrazoline-β-lactams and spirocyclopropyl-β-lactams from 6-alkylidenepenicillanates

Chiral spiropyrazolinepenicillanates were obtained in a stereoselective fashion via 1,3-dipolar cycloaddition reactions of 6-alkylidenepenicillanates with diphenyldiazomethane, phenyldiazomethane, and diazomethane. Microwave-induced ring contraction of spiro-1-pyrazoline-β-lactams leading to chiral spirocyclopropylpenicillanates is also described.     

Synthesis,characterization and redox properties of mono- and bis-β-diketonate ruthenium complexes

Complexes of the type [RuIII(L)Cl2(PPh3)2] and [RuII(L)2(PPh3)2] (HL=benzoylacetone or acetylacetone) have been synthesized by the reaction of [RuCl2(PPh3)3] with HL under various experimental conditions. The [RuIII(L)Cl2(PPh3)2] complexes are one-electron paramagnetic species and, in solution, they show intense LMCT transitions in the visible region together with weak ligand-field transitions at lower energies. The [RuII(L)2(PPh3)2] complexes are diamagnetic and their solutions show sharp 1H n.m.r. signals and also show intense MLCT transitions in the visible region. In MeCN solution, the [RuIII(L)Cl2(PPh3)2] complexes show a reversible RuIII-RuII reduction near –0.3V and an irreversible RuIII- RuIV oxidation near 1.2 V versus s.c.e. A reversible RuII-RuIII oxidation is displayed by the [RuII(L)2(PPh3)2] complexes in MeCN solution near 0.3 V versus s.c.e. followed by another reversible RuIII-RuIV oxidation near 1.1 V versus s.c.e. The [RuII(L)2(PPh3)2] complexes have been oxidized to the corresponding [RuIII(L)2(PPh3)2]+ analogues and isolated as ClO4– salts in the solid state. The oxidized complexes are one-electron paramagnetic. They are 1:1 electrolytes in solution and show intense LMCT transitions in the visible region along with weak ligand-field transitions at lower energies.     

Synthesis of novel β-amino ketones containing a p-aminobenzoic acid moiety and evaluation of their antidiabetic activities

The synthesis of two series of β-amino ketones containing a p-aminobenzoic acid moiety (TM-1 and TM-2) using a modified protocol of the Mannich reaction is reported. The molecular structures of a total of tweenty three new target compounds were characterized by 1H NMR, 13C NMR, ESI-MS and HR-MS. Subsequently, their antidiabetic activities were screened in vitro. The α-glucodase inhibition (α-GI) activity of compound 1e reached a remarkable level of 66.50%. The peroxisome proliferatoractivated receptor (PPAR) relative activation activities of six compounds are above 80%, and in particular 2i displays an unprecedentedly high PPAR of 130.91%. The structure-activity relationships of the compounds were established. 2i is also subject to further in-depth investigation.     

Synthesis of 1-indolyl substituted β-carboline natural products and discovery of antimalarial and cytotoxic activities

A series of 1-indolyl substituted β-carbolines including the natural products hyrtiosulawesine, pityriacitrin and pityriacitrin B were prepared via Pictet–Spengler condensation—oxidation strategy from the corresponding indolyl-acetaldehydes and substituted tryptamines. Efforts to prepare the C-1 methylene-linked β-carboline analogues for structure–activity relationship studies were unsuccessful. Biological evaluation revealed two analogues (5 and 41) to exhibit weak inhibition of phospholipase A₂ (IC₅₀ 171 and 131 μM, respectively), two to act as antioxidants (3 and 43), and 12 analogues with activity towards a chloroquine-resistant strain (FcB1) of Plasmodium falciparum (IC₅₀ 1.0–23 μM). Testing against a panel of 60 human tumour cell lines revealed a general lack of cytotoxic effect for most of the compounds with the exception of β-carboline 42 exhibiting modest antileukaemic activity towards the HL-60(TB) cell line (LC₅₀ 4.2 μM). In addition, two novel structures (30 and 32) resulting from aldol condensation followed by Pictet–Spengler cyclisation displayed cytotoxicity with pronounced subpanel specificities towards colon cancer (COLO 205 and HCC-2998) cell lines.     

β-lactams from esters and silylimines: A revaluation. Synthesis of N-unsubstituted 4-alkyl-β-lactams

The first preparation of enolizable silylimines is reported. The “in situ” trapping of these species with lithium enolates of esters gives rise in fairly good yields to N-unsubstituted 4-alkyl-β-lactams.     

Synthesis and biology of N-thiolated β-lactams

N-Thiolated β-lactams are an interesting new family of bioactive agents having antibacterial, antifungal, and anticancer capabilities. Our interest in these β-lactams stems from their highly unusual structure–activity profiles and selectivity toward only a few genera of pathogenic bacteria, including Staphylococcus aureus, Bacillus anthracis, and Micrococcus. Here, we provide a complete outline on our work in the discovery and ongoing development of these compounds, starting from our initial, unexpected finding of antimicrobial activity for one of the lead compounds, to a more complete understanding of their chemical and biological mode of action and potential utility as antibacterial compounds.     

Design,synthesis, activity evaluation and QSAR studies of novel antimalarial 1,2,3-triazolo-β-lactam derivatives

This paper describes the synthesis of some new β-lactam derivatives containing the 1,2,3-triazole moiety. All the compounds were evaluated for their in vitro antimicrobial and antimalarial activities. Moderate to excellent antimalarial activities were encountered. The results showed that compounds 5a, 5c, 5f, 5i exhibited the most potent antimalarial activity with IC₅₀ values of 0.85, < 0.97, < 0.97, 1.81 µM against chloroquine-resistant P. falciparum K1 strain. A QSAR study highlights the structure–activity relationships that correlate the observed antimalarial activities with changes in the compounds’ structural features.     

N-glycyl-β-glycopyranosylamines, derivatives of mono- and disaccharides, and their use for the preparation of carboxylic acid glycoconjugates

A convenient preparative procedure was developed for the synthesis ofN-glycyl-β-glycopyranosylamines, derivatives of monosaccharides (d-galactose,d-mannose,l-fucose, andN-acetyl-d-glucosamine) and disaccharides (lactose, melibiose, cellobiose, and maltose). These compounds were demonstrated to be useful for the preparation of glycoconjugates of biologically active compounds containing the carboxy group (nicotinic, orotic, kynurenic, and indoleacetic acids). Synthetic pathways were developed for conversions ofN-glycyl-β-glycopyranosylamines into derivatives containing the carboxy group with the use of malonic andl-tartaric acid derivatives. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1461–1466, August, 2000.     

Synthesis of Z-β-siloxyacrylonitriles and study of their dienophilic properties

A general method for the synthesis of Z-β-siloxyacrylonitriles from isoxazoles is reported. Their dienophilic activity is also described.     

Synthesis,characterization and antimalarial activity of new iridium–chloroquine complexes

Chloroquine base (CQ) reacts with [Ir(COD)Cl]₂ and IrCl₃ · 3H₂O to yield of Ir(CQ)Cl(COD) (1) and Ir₂Cl₆(CQ) · 3H₂O (2), respectively. Reaction of [Ir(COD)Cl]₂ with CQ in the presence of NH₄PF₆ leaded to [Ir(CQ)(Solv)₂]PF₆ (3). The three new iridium–CQ complexes were characterized by a combination of elemental analysis, IR and NMR spectroscopies and evaluated in vitro against Plasmodium beghei. Comparison of the IC₅₀ values obtained with the experimental compounds with that determined for chloroquine diphosphate indicated a higher activity for complex 2, while complexes 1 and 3 showed a similar and lower activity, respectively.     

Synthesis of fluorescent fluorene–isoindole-containing mono- and oligomers

Novel fluorene–isoindole-containing light-emitting mono- and oligomers were prepared. The synthesis of the monomers N-(4-bromo-phenyl)-2-(7-bromo-9,9-diethylfluoren-2-yl)-isoindole-1-carboxamide, N-(7-bromo-9,9-dibutylfluoren-2-yl)-2-(7-bromo-9,9-dibutylfluoren-2-yl)-isoindole-1-carboxamide, and N-[7-bromo-9,9-bis(2-ethylhexyl)-fluoren-2-yl]-2-[7-bromo-9,9-bis(2-ethylhexyl)-fluoren-2-yl]-isoindole -1-carboxamide was carried out by a three-component reaction of ortho-phthalaldehyde with the corresponding amine and isocyanide partners. The Ni(0) mediated polymerization reactions of the obtained monomers gave the corresponding mixture of oligomers from two up to twelve repeat units. The optical properties were also studied and it was found that the phenylene-containing oligomer emitted green light in dichloromethane solution, while both difluorene-containing oligomers, under the same conditions, proved to be blue light-emitters with good quantum efficiency.     

Synthesis of natural maleimides farinomaleins C–E and evaluation of their antifungal activity

A practical and convenient synthesis of naturally occurring farinomaleins C–E was achieved starting from readily available ethyl 3-methyl-2-oxobutyrate and triethyl phosphonoacetate. The key steps of the sequence included a Horner–Wadsworth–Emmons condensation to obtain the precursor farinomalein A and coupling with suitable alcohols to install the chain. The synthesis of farinomalein D has been achieved starting from (R)-isopropylideneglycerol on the basis of which the S configuration was assigned to the natural compound. The antifungal activity of the synthesized compounds was evaluated against Cladosporium cladosporioides.     

Synthesis of 7-O-β-D-glucopyranosides of isoflavones and their heterocyclic analogues

The products of the interaction of -acetobromoglucose with 2,4,5-trihydroxyphenyl benzyl ketone and 2,4-dihydroxyphenyl 4-hydroxybenzyl ketone and also with their heterocyclic analogues, which are present completely or partially in the enolic form, have been investigated. It has been shown that in this reaction a tetra-O-acetylglucosyl residue is added at the 4-OH hydroxy group of the phenyl residue of the ketone. The compounds obtained have been converted into isoflavone 7-O-glucosides by the action of the vilsmeier reagent or acetoformic anhydride.Taras Shevchenko Kiev University. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 220–227, March–April, 1993.     

Synthesis of mono- and di-α-l-fucosylated 2-acetamido-2-deoxy-N-glycyl-β-d-glucopyranosylamines,spacered fragments of glycans of N-glycoproteins

Russian Chemical Bulletin - α-l-Fucp-(1→3)-d-GlcNAc, α-l-Fucp-(1→6)-[α-l-Fucp-(1→3)]-d-GlcNAc, and β-d-Galp-(1→3)-[α-l-Fucp-(1→4)]-d-GlcNAc...