The synthesis and anti-tumoral properties of a series of compounds possessing a ferrocenyl group tethered to a catechol via a conjugated system is presented. On MDA-MB-231 breast cancer cell lines, the catechol compounds display a similar or greater anti-proliferative potency (IC(50) values ranging from 0.48-1.21 μM) than their corresponding phenolic ...

A regioselective route to novel mono triazolyl substituted quinolines has been developed via copper-catalyzed azide-alkyne cycloaddition (CuAAC) of 2,4-diazidoquinoline with terminal alkynes in DMF. The reaction provided bis triazolyl substituted quinolines when performed in water in the presence of Et(3)N. A number of the compounds synthesized showed promising anti-proliferative properties ...

ABCG2 plays a major role in anticancer-drug efflux and related tumor multidrug resistance. Potent and selective ABCG2 inhibitors with low cytotoxicity were investigated among a series of 44 chalcones and analogs (1,3-diarylpropenones), by evaluating their inhibitory effect on the transport of mitoxantrone, a known ABCG2 substrate. We identified six compounds ...

A series of novel 1,2,3,4-tetrahydro[1,2,4]triazino[4,5-a]benzimidazoles carrying variety of aryl and heteroaryl groups at position 1 were synthesized. The newly synthesized compounds were tested in vitro on human breast adenocarcinoma cell line (MCF7). Some of the test compounds showed potent antitumor activity, especially compound 3c [1-(2-chlorophenyl) derivative] which displayed the highest activity ...

A fast and efficient nickel-catalysed iodination reaction of aryl and heteroaryl bromides has been developed. The transformation was found to be general for a wide range of substrates and was used for the synthesis of iodo-PK11195, an imaging agent of Alzheimer's disease and iniparib, a compound used in the treatment ...

Three new dimeric indole alkaloids (1-3), together with five known ones (4-8), were isolated from the whole plants of Catharanthus roseus. The structures and absolute configurations of new compounds were elucidated by means of NMR and CD analyses. All these compounds were evaluated for their in vitro cytotoxic activities against ...

A series of 1,2,4-triazole derivatives containing thiosemicarbazone linkage was synthesized and evaluated for their in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. All the compounds were capable of inhibiting the growth of E. histolytica out of which four compounds (IC(50)=0.28-1.38μM) were found to have better efficacy than the ...

A series of PI3K-beta selective inhibitors, imidazo[1,2-a]-pyrimidin-5(1H)-ones, has been rationally designed based on the docking model of the more potent R enantiomer of TGX-221, identified by a chiral separation, in a PI3K-beta homology model. Synthesis and SAR of this novel chemotype are described. Several compounds in the series demonstrated potent ...

Previously, we reported that 4-amino-2H-benzo[h]chromen-2-one (ABO) and 4-amino-7,8,9,10-tetrahydro-2H-benzo[h]chromen-2-one (ATBO) analogues, which were developed from the lead natural product neo-tanshinlactone, are potent cytotoxic agents. In order to improve on their water solubility, the diamino analogues and related salts were designed. All synthesized compounds were assayed for cytotoxicity, and selected compounds were ...

We have recently established that drugs used for the treatment and the prophylaxis of breast cancers such as tamoxifen were potent inhibitors of cholesterol-5,6-epoxide hydrolase (ChEH), which led to the accumulation of cholestan-5α,6α-epoxy-3β-ol (α-CE) and cholestan-5β,6β-epoxy-3β-ol (β-CE). This could be considered as a paradox since epoxides are known as alkylating ...

In an effort to develop effective antiamoebic agents, some hydrazones and azoles containing pyridyl moiety were synthesized and screened for in vitro antiamoebic activity against HM1:IMSS strain of Entamoeba histolytica. Among all the compounds, only five compounds (1, 3, 5, 9 and 11) were found to be better inhibitors of growth ...

The synthetic utility of 3,3'-(3,4-dimethylthieno[2,3-b]thiophene-2,5-diyl)bis (3-oxopropanenitrile) (1) in the synthesis of some novel bis-[1,3,4-thiadiazole] 6a-g and bis-thiazole 10 and 13 derivatives with thieno[2,3-b]thiophene moiety is reported. Antimicrobial evaluation of some selected examples from the synthesized products was carried out and showed promising results.

Twelve new hydroquinones and quinones (4a-c to 7a-c) derived from free or peracetylated bile acids were prepared by a Barton decarboxylation reaction, with subsequent trapping of the resulting free radical by benzoquinone. All new compounds were completely characterized by 2D NMR techniques and screened for antifungal and cytotoxic activity. One ...

Wear and damage of ultrahigh molecular weight polyethylene (UHMWPE) tibial inserts used in total knee arthroplasty are accelerated by oxidation. Radiation crosslinking reduces wear but produces residual free radicals adversely affecting stability. One alternative to stabilize radiation-crosslinked UHMWPE is to infuse the material with vitamin E (vit E). We investigated ...

The objective of this study was to determine the effects of dietary treatment and packaging on the oxidative stability of breast rolls. A total of 120 4-wk-old broiler chickens were randomly assigned to control, oxidized diet (5% oxidized oil, PV = 100), or antioxidants-added diet (500 IU vitamin E + ...

A detailed description of our second-generation total synthesis of salinosporamide A is presented. Three contiguous stereocenters in the γ-lactam structure seen in the natural product were established by stereoselective functionalization of a D-arabinose scaffold, including an Overman rearrangement to generate a highly congested tetrasubstituted carbon center. One of the definitive ...

Lactams are an important class of compounds owing to their presence in numerous biologically active molecules of natural and unnatural nature. They are also highly versatile intermediates that can be elaborated into interesting compounds for potential use in organic and medicinal chemistry endeavors. In this feature article, the reader will ...

Acyclic N-C(α)-branched, N-bis(trimethylsilyl)methyl (N-BTMSM) diazoamides undergo regio-, chemo-, and diastereoselective Rh(II)-carbenoid C-H insertion to give 4,5-disubstituted and 3,4,5-trisubstituted γ-lactams. The conformational influence of the N-BTMSM group and the electronic effect of the O-pivaloyl moiety of the C(α)-oxymethylene unit are essential for the observed regioselectivity. The synthesis of α-allokainic acid demonstrates ...

An expedient diastereoselective synthesis of highly functionalized indolo[2,3-α]quinolizidines adopting a cis H2/H12b geometry has been realized by a Pictet-Spengler/lactamization cascade sequence. The absolute stereochemistry at C2, C3, and C12b was governed by the originally created chirality of the Michael adduct through organocatalyzed conjugate addition of dialkyl malonates to α,β-unsaturated aldehydes.

The first synthesis of heliotropamide is reported. The preparation of this 2-oxopyrrolidine (γ-lactam) natural product relied on a diastereoselective one-pot, four-component reaction (4CR) for the assembly of the core structure. On the basis of chemical shift correlation and NOESY experiments, the previously unknown alkene geometry of heliotropamide is assigned as ...

Some bicyclic C-fused chlorinated tetrahydrofuro[3,2-c]azetidin-2-ones were prepared by a fairly general route involving Staudinger reaction of allylic/propargylic imidates with dichloroketene followed by highly diastereoselective CuCl/PMDETA-catalyzed 5-exo-trig/dig chlorine atom transfer radical cyclization. An oxepan-fused β-lactam was also prepared similarly by 7-endo-trig cyclization. Synthetic application of the side chain chlorine atom of ...

An efficient one-pot asymmetric synthesis of highly substituted γ-lactams containing α-methylene groups has been successfully developed. A wide range of γ-lactams could be obtained in high yields with excellent diastereomeric ratios of up to 99:1 in favor of trans isomers. In particular, excellent enantioselectivities of the two newly formed stereogenic ...

In the Amazonian agricultural frontier, pasture for cattle ranching is an important and potentially hazardous form of land use because of sediment erosion as pastures degrade. This relationship between ranching, sediment load, and water quality is likely to further exacerbate environmental impacts, particularly in the context of climate change. We ...

The tetracyclic framework of the tetrapetalone A aglycon has been secured through synthesis. A reductive pyrrole alkylation enables the formation of a key tetrasubstituted carbon stereocenter, and the tetramic acid portion of the molecule can be accessed through silicon or boronic ester conjugate addition to an ene-lactam.

The first synthesis of isaindigotidione has been developed utilizing a reaction sequence including an asymmetric rhodium-catalyzed 1,4-conjugate addition, an intramolecular aldol reaction, and a lactamization.

The synthesis and study of the structure-activity relationships of a series of rigid analogues of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone (β-lactam) ring system in place of the usual ethylene bridge present in the natural combretastatin stilbene products. The 1,4-diaryl-2-azetidinones are unsubstituted at C-3, or contain methyl substituent(s) ...

meso-Cyclic imides are monohydrogenated to form the corresponding hydroxy lactams in 88-97% ee using trans-[Ru((R)-BINAP)(H)(2)((R,R)-dpen)] and related compounds as catalysts with base in THF. The hydrogenation proceeds with high enantiogroup- and chemoselectivity, and it is a desymmetrization reaction, forming up to five stereogenic centers in one reaction. Conversion of a ...

A highly enantio- and diastereoselective Lewis acid catalyzed S(N)2-type ring opening followed by cyclization of aziridines with active methylene carbon nucleophiles to functionalized chiral γ-lactams in a domino fashion has been developed. γ-Lactams have been desulfonated and decarboxylated, providing pyrrolidone-3-carboxylate and N-tosylpyrrolidinone derivatives, respectively, in good yields.

The microwave-assisted Wolff rearrangement of cyclic 2-diazo-1,3-diketones in the presence of primary amines and α,β-unsaturated aldehydes provides a straightforward three-component stereoselective access to a variety of α-spiro-δ-lactams following an imination/Wolff rearrangement/[2 + 4] cycloaddition domino sequence. With aniline derivatives, a complementary aza-Wittig/Wolff rearrangement/[2 + 4] sequence was developed. These reactions ...

Aziridinomitosane ketones 4 and 24 are accessed by internal acyl anion equivalent-lactam cyclization of 29 in a convergent route. The key aziridinolactam 6 is prepared by tin-lithium exchange via the lithiated aziridine 11.

beta-lactam antibiotics are the agents most frequently implied in immune drug adverse reactions. These can be classified as immediate or nonimmediate according to the time interval between the last drug administration and their onset. Mechanisms of immediate IgE-mediated reactions are widely studied and are therefore better understood. Nonimmediate reactions include ...

Catalyzed by Rhodococcus erythropolis AJ270, a nitrile hydratase and amidase containing microbial whole cell catalyst, a number of racemic 1-arylmethyl- and 1-allyl-4-oxoazetidine-2-carbonitriles and carboxamides underwent efficient transformations under very mild conditions to produce enantiopure functionalized S-amide and R-acid products in excellent yields. While the nitrile hydratase showed good enzyme activity ...

The quantitative removal of contaminant antibiotic activity from waters intended for reuse is one of the biggest problems facing water utilities today. As conventional water treatments are not sufficient, advanced Oxidation and Reduction Processes (AO/RPs) are being considered for additional remediation. In support of the potential use of sulfate radical ...

Regio- and diastereoselective reactions of a homoproline enolate enable the synthesis of novel extended dipeptide surrogates. Bicyclic carbamate 9 and fused beta-lactam scaffold 11 were prepared from L-pyroglutamic acid via substrate-controlled electrophilic azidation. Synthesis of orthogonally protected hexahydropyrrolizine, hexahydropyrrolizinone, and hexahydropyrroloazepinone dipeptide surrogates relied on allylation of proline derivative 5, ...

Reactions of ozone (O3) with the beta-lactam antibiotics penicillin G (PG) and cephalexin (CP) have previously been found to yield products retaining antibacterial activities. These products are unequivocally identified here as the stereoisomeric (R)-sulfoxides of each parent molecule and characterized by a combination of chemical analysis and an antibacterial activity ...

Three new metabolites having a spiro-heterocyclic gamma-lactam core, cephalimysins B-D (1-3), as well as FD-838 (4) were isolated from a culture broth of Aspergillus fumigatus that was originally separated from the marine fish Mugil cephalus. Compounds 1-3 are the diastereomers of 4. Compounds 2 and 3 exhibit an opposite absolute ...

The scope and limitations of the intramolecular 1,6-addition of an enolate to a 2-pyridone moiety, a reaction that has found application in the synthesis of the lupin alkaloids, have been probed. This nucleophilic addition process has been shown to be reversible and favored in the case of (less stabilized) amide ...

A one-pot, three-step tandem process has been developed for the direct synthesis of functionalised bicyclic [3.3.0], [4.3.0] and [5.3.0] gamma-lactams from simple allylic trichloroacetimidates. The process involves a palladium(ii) mediated Overman rearrangement followed by the use of Grubbs first generation complex which catalyzes both a ring closing metathesis reaction and ...

A new Morita-Baylis-Hillman reaction methodology in which alkyl halides and epoxides act as electrophiles in their reaction with lactones and lactams is shown. Catalysis is efficiently performed by hydroxy sulfides under basic conditions. The procedure works efficiently with many alkyl halides but fails with aldehydes with which a conventional acid-catalyzed ...

Photochemical or thermal reactions of 3-(2-azidobenzylidene)-lactams afforded fused indoles such as indolo[3,2-c]quinolin-6-ones, pyrido[4,3-b]indol-1-ones and other similar compounds in moderate to high yields via cyclization-ring expansion reactions. The photolytic process was much more facile than the thermal process and could be further improved by addition of CuI.

Synthesis of novel beta-lactam fused spiroisoxazolidine chromanones and tetralones ring systems has been achieved by intermolecular 1,3-dipolar cycloaddition reaction of bicyclic nitrone with unusual dipolarophiles, arylidene chromanones/tetralones under different reaction conditions. The synthesized compounds were evaluated for antimicrobial activities. It was observed that two of the synthesized compounds exhibited relatively ...

Spirocyclic carbazole- and acridine-lactams were prepared by Fischer-indole or Friedländer-quinoline synthesis starting from spirocyclic ketones with a lactam ring. All annulation products were obtained as mixtures of separable regioisomers, which differ only in the position of one methyl group. The starting materials were prepared from 2-pyrrolidone and 2-piperidone by a ...

A new synthetic strategy for construction of the heptacyclic marine fungal alkaloid (+/-)-communesin F has been devised. Key reactions include an intramolecular Heck cyclization of a tetrasubstituted alkene to generate a tetracyclic enamide bearing one of the quaternary carbon centers (C7) of the alkaloid, an intramolecular reductive cyclization of an ...

A facile, versatile and stereoselective synthesis of bicyclic polyhydroxylated alkaloids as castanospermine analogues is described. The synthetic route started from methyl pyranosides. The key steps involved a high-yielding expeditious one-pot tandem reaction from alkenes to N-substituted delta-lactams. The delta-lactams were stereoselectively vinylated to give the dienes, which were followed by ...

Two new hetero-spirocyclic gamma-lactams, azaspirofurans A (1) and B (2), had been isolated from a marine sediment-derived fungus Aspergillus sydowi D2-6. Their structures were determined by the chemical evidence and spectral analyses. Compound 1 exhibited cytotoxicity against A549 cell line with the IC50 value of 10 microM by MTT method.

An efficient and highly regioselective protocol was developed for the preparation of 5-hydroxy-2-isoxazolines, which have been proved to be versatile synthons for isoxazles, beta-hydroxy oximes, and gamma-amino alcohols. Beta-lactams, commonly embedded in the skeletons of bioactive natural products, were also synthesized in two steps from beta-hydroxy oximes, providing a new ...

The "Staudinger ketene-imine reaction" between ketenes generated from natural O,N-protected trans-4-hydroxy-l-prolines and the N-benzyl-N-benzylideneamine led to mixtures of diastereoisomeric, enantiomerically pure pyrrolidine-derived spiro-beta-lactams with a relative cis configuration. These were transformed into the corresponding pyrroline-spiro-beta-lactams by means of treatment with a base and the new C=C double bond was submitted ...

Polycyclic iminium ethers are ambident electrophilic intermediates that react with a range of nucleophiles in a highly condition-dependent manner to afford densely functionalized lactams. In an effort to expand the scope of reactivity and assist in the generation of new chemotypes from these intermediates, several iminium ethers were subjected to ...

Unsaturated lactams with endo- or exocyclic C-C double bonds constitute a set of reactive inputs that serve as the electron-rich olefin component in Povarov reactions. These substrates afford the multicomponent adducts in convenient yields and offer a wide range of structural diversity. Postcondensation transformations allow direct access to a variety ...

Synthetic strategies toward 4-substituted 3,3-difluoropiperidines were evaluated. 4-Alkoxymethyl- and 4-aryloxymethyl-3,3-difluoropiperidines were synthesized via 1,4-addition of ethyl bromodifluoroacetate to 3-substituted acrylonitriles in the presence of copper powder, followed by borane reduction of the cyano substituent, lactamization, and reduction of the lactam. This method was applied to establish the synthesis of N-protected ...