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A novel 1,4-conjugate addition/esterification of ortho-quinone methides in a multicomponent reaction has been developed. In this protocol, numerous carboxylic acids, ynamides and in situ generated ortho-quinone methides could assemble rapidly to constitute this process for the synthesis of functionalized 3,3-diarylpropanamides with sufficient structural diversity. Furthermore, the products could be transformed to an array of compounds. [ABSTRACT FROM AUTHOR]

The enantioselective incorporation of alkyl groups in thiochromones was realized for the first time by a Cu/(R,S)-PPF-PtBu2- catalyzed conjugate addition of Grignard reagents to thiochromones. With this method, a series of 2-methylthiochromanones were obtained in good yields (up to 96% yield) with moderate-to-good ee values (up to 87% ee). The established method expedites the synthesis of a large library of chiral thiochromanones for further synthetic applications and biological studies. [ABSTRACT FROM AUTHOR]

Recently, ionic liquids (ILs) have been regarded as ideal media for non-aqueous bio-catalysis. In this work, the synthesis of warfarin by the lipase-catalyzed Michael addition in IL media and the parameters that affected the warfarin yield were investigated. Experimental results demonstrated that the chemical structures of the ILs were a major factor for influencing the warfarin yield. The ILs containing the NTf2- anion were suitable reaction media due to the high chemical stability of this anion. The incorporation of the hydroxyl group on the IL cation significantly improved the lipase activity due to the H2O-mimicking property of this group. The lipase activity decreased by increasing the alkyl chain length on the IL cation due to the non-polar domain formation of the IL cation at the active site entrance of lipase. The ILs and lipase could be reused no less than five times without reduction in the warfarin yield. [ABSTRACT FROM AUTHOR]

Abstract: A highly enantioselective sulfa‐Michael addition of tritylthiol to azadienes catalyzed by a bifunctional squaramide organocatalyst is described, giving the chiral aminothioethers bearing benzofuran motif with high yields and up to 94 % of enantioselectivity. Notably, the aromatization to form the benzofuran is the driving force. [ABSTRACT FROM AUTHOR]

Asymmetric construction of β,β-diaryl substituted glycine bearing two contiguous chiral centers remains a significant challenge. Herein, the application of the para -quinone methides ( p -QMs) and Ni(II)- complex of glycine via 1,6-conjugate addition to achieve asymmetric synthesis of β,β-diaryl substituted glycine has been explored successfully. This protocol features operational simplicity, high diastereoselectivity, and recyclable chiral ligand, which provides a versatile approach to the synthesis of highly enantiopure β,β-diaryl substituted glycine. [ABSTRACT FROM AUTHOR]

N-cyanoethyl polyethylenimine (CN-PEI) is synthesized by modifying polyethylenimine (PEI) with acrylonitrile through a Michael addition reaction. Depending on cyanoethylation level, CN-PEI can be obtained as a form of solution, micro-emulsion or emulsion in water. CN-PEI micro-emulsion is investigated as water-soluble binder for the application of lithium iron phosphate (LFP) cathode in lithium-ion batteries. CN-PEI binder not only maintains the outstanding dispersion capability of PEI but also exhibits an excellent adhesion strength and higher ionic conductivity because of the introduction of polar cyano groups. As a result, CN-PEI binder can effectively maintain the mechanical integrity and decrease the polarization of LFP electrode during the operation of the battery. LFP electrode with CN-PEI binder exhibits good cycle stability and enhanced rate performance delivering a capacity of 99.6% at a rate of 0.5 C after 100 cycles and a high discharge capacity of 102.4 mAh g−1 at 5 C. [ABSTRACT FROM AUTHOR]

Abstract: A tetracyclic dinitrile was synthesized in twelve steps from cyclohex‐2‐en‐1‐one by using a chelation‐triggered conjugate addition to a γ‐hydroxy‐substituted α,β‐unsaturated nitrile and an oxidative dearomatization/Diels–Alder cycloaddition cascade as the key steps. The first total synthesis of azitine (in 17 steps) was achieved through a simple reductive cyclization of this intermediate and subsequent transformations while the total synthesis of the proposed structure of navirine C (in 19 steps) was accomplished by a hydrogen‐atom‐transfer reaction of the tetracyclic dinitrile, Pd/C‐catalyzed reductive cyclization, and subsequent functional group manipulation. [ABSTRACT FROM AUTHOR]

Abstract: Herein, we present a new desulfurative method for generating primary, secondary, and tertiary alkyl radicals through visible‐light photoredox catalysis. A process that involves the generation of N‐centered radicals from sulfinamide intermediates, followed by subsequent fragmentation, is critical to forming the corresponding alkyl radical species. This strategy has been successfully applied to conjugate addition reactions that features mild reaction conditions, broad substrate scope (>60 examples), and good functional‐group tolerance. [ABSTRACT FROM AUTHOR]

In this paper, we describe our efforts toward the asymmetric synthesis of Daphniphyllum alkaloid 21-deoxymacropodumine D which led to efficient preparation of a ABC tricyclic framework containing five consecutive stereocenters. This synthetic work features (1) utilization of an asymmetric conjugate addition to install the C5 all-carbon quaternary center, (2) an intramolecular aza -Michael addition followed by Pd-catalyzed α -alkenylation to build the bowl-shaped tricyclic core. [ABSTRACT FROM AUTHOR]

A conjugate addition of diverse nucleophiles to acylketene acetals derived from 1,8-dihydroxynaphthalene (DHN) is developed for the formation of its 3-oxoalkan-1-one acetals. The initial acylketene acetals are prepared via double oxa-Michael addition of DHN to 1-bromo-1-propyn-3-ones. Carbonucleophiles, including organocopper reagents and active methylene compounds, and heteroatom nucleophiles were introduced under basic conditions. This method is applied for synthesizing spiropreussione A; the proposed structure does not correspond to that of the authentic natural product. [ABSTRACT FROM AUTHOR]

Amide pronucleophiles were successfully incorporated into a 1,6-conjugate addition reaction manifold using p-quinone methides (p-QMs) as electrophiles. Four different types of functionalities were tolerated as α-substituents of the amides, allowing for expeditious access to a range of enantiomerically enriched diarylmethine products. The 7-azaindoline unit is critically important for in situ catalytic enolization of the amide pronucleophile, engaging in 1,6-conjugate addition to p-QMs with readily available catalyst components. [ABSTRACT FROM AUTHOR]

The PBu 3 -catalyzed conjugate addition of diphenylphosphine oxide to unsubstituted and substituted electron-deficient alkenes is reported. β-Substituted α,β-unsaturated esters, trans -methyl crotonate and trans -methyl cinnamate, known for their reluctance to participate in phosphine-catalyzed transformations, also react well under the developed conditions. Mild reaction conditions, simple work-up and the ease of catalyst recovery make the proposed methodology useful for the preparation of functionalized tertiary phosphine oxides. The utility of this method was demonstrated by the gram-scale reactions of diphenylphosphine oxide with electron-deficient alkenes. [ABSTRACT FROM AUTHOR]

Abstract: A simple ruthenium‐catalyzed conjugate addition of C−H bonds to α,β‐unsaturated ketones directed by a removable carboxyl group was developed as an effective protocol to synthesize ortho‐alkylated benzoic acids in a greener manner. Without any additives, satisfactory to excellent yields of the targeted products were achieved in neat water, and the process characterizes in mild reaction conditions (in air and water), simple operations, and broad substrate scope. Noteworthy features of this method include mild reaction conditions (in air and water), operational simplicity and broad substrate scope. The versatility and utility of the addition products were demonstrated through further transformation into commonly inaccessible but highly useful motifs of meta‐substituted alkylbenzenes and 3‐substituted isochromanones. [ABSTRACT FROM AUTHOR]

A facile one-pot method for the synthesis of iodine-substituted 1,4-oxazepines is reported. When reacted with ZnCl 2 and I 2 in DCM at 40 °C, N -propargylic β-enaminones, prepared by the conjugate addition of propargylamine to α,β-alkynic ketones, underwent 7-exo-dig cyclization by zinc chloride and concomitant reaction with molecular iodine to afford 2-(iodomethylene)-2,3-dihydro-1,4-oxazepines in good to high yields. This cyclization was found to occur with broad scope of substrates and high tolerance of functional groups. The resulting iodine-containing 1,4-oxazepines can be further elaborated to more complex structures by subsequent cross-coupling reactions, which may provide a platform for biological studies. [ABSTRACT FROM AUTHOR]

Abstract: A facile visible‐light photocatalytic conjugate addition to prepare 1,4‐dicarbonyl compounds has been developed by employing readily available aroyl chlorides as aryl radical sources. This operationally simple method shows a broad scope with regard to both aroyl chlorides and Michael acceptors. As a result, a variety of 1,4‐diketones were efficiently synthesized in moderate to good yields. [ABSTRACT FROM AUTHOR]

A novel, efficient transition-metal-free and controllable boration/protodeboronation strategy has been developed for the chemoselective conjugate addition and 1,4-reduction of α,β-unsaturated carbonyl compounds. Without any metal-catalyst or base, a series of β-boration products of α,β-unsaturated carbonyl compounds was easily obtained in moderate to excellent yields in a mixed solvent of ethanol and water. The presence of a catalytic amount of Cs2CO3 can effectively induce further protodeboronation reaction towards 1,4-reduction products at higher reaction temperature. Therefore, by slightly changing the reaction conditions, the boration or reduction products of α,β-unsaturated carbonyl compounds can be controllably obtained. Mechanistic studies revealed that Cs2CO3 played the key role in activating the protodeboronation step. This transition-metal-catalyst-free and product controllable method provides a useful and eco-friendly tool for the highly chemoselective preparation of the β-boration products and 1,4-reduction products of α,β-unsaturated carbonyl compounds. [ABSTRACT FROM AUTHOR]

α-Selenoenones could be employed as Z-allyl precursors in the chiral amine-catalyzed asymmetric conjugate addition of aldehydes. The obtained formal allylation product, a Z-olefin having a sulfonate leaving group, was employed as a synthetically useful chiral alkylating agent. [ABSTRACT FROM AUTHOR]

We report here the silylation of α,β‐unsaturated acceptors in water at room temperature using a copper catalyst. A broad substrate scope, including chalcone derivatives, esters, nitrile, and dienones, has been explored. In all cases, the reaction proceeded well to give the desired products in good to excellent yield. [ABSTRACT FROM AUTHOR]

Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody-drug conjugate for the treatment of acute myeloid leukemia (AML). Although GO shows a narrow therapeutic window in early clinical studies, recent reports detailing a modified dosing regimen of GO can be safely combined with induction chemotherapy, and the combination provides significant survival benefits in AML patients. Here we tested whether the survival benefits seen with the combination arise from the enhanced reduction of chemoresidual disease and leukemic initiating cells (LICs). Herein, we use cell line and patient-derived xenograft (PDX) AML models to evaluate the combination of GO with daunorubicin and cytarabine (DA) induction chemotherapy on AML blast growth and animal survival. DA chemotherapy and GO as separate treatments reduced AML burden but left significant chemoresidual disease in multiple AML models. The combination of GO and DA chemotherapy eliminated nearly all AML burden and extended overall survival. In two small subsets of AML models, chemoresidual disease following DA chemotherapy displayed hallmark markers of leukemic LICs (CLL1 and CD34). In vivo, the two chemoresistant subpopulations (CLL1+/CD117- and CD34+/CD38+) showed higher ability to self-renewal than their counterpart subpopulations, respectively. CD33 was coexpressed in these functional LIC subpopulations. We demonstrate that the GO and DA induction chemotherapy combination more effectively eliminates LICs in AML PDX models than either single agent alone. These data suggest that the survival benefit seen by the combination of GO and induction chemotherapy, nonclinically and clinically, may be attributed to the enhanced reduction of LICs. [ABSTRACT FROM AUTHOR]

A pyrrolidine–diaminomethylenemalononitrile organocatalyst efficiently promotes the asymmetric direct bisvinylogous Michael addition of 5-benzylfurfural derivatives to nitroalkenes, affording the corresponding ε-regioselective addition products in high yields with up to 86% ee. [ABSTRACT FROM AUTHOR]

The asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680 are reported. Conjugate addition of lithium ( R )- N -benzyl- N -(α-methylbenzyl)amide to the requisite ( E )-α,β-unsaturated ester followed by in situ enolate oxidation with (−)-(camphorsulfonyl)oxaziridne (CSO) gave the corresponding anti -α-hydroxy-β-amino esters. Sequential Swern oxidation followed by diastereoselective reduction gave the corresponding syn -α-hydroxy-β-amino esters. Subsequent N-debenzylation (i.e., hydrogenolysis for microginin 612, and NaBrO 3 -mediated oxidative N-debenzylation for microginins 646 and 680) followed by acid catalysed ester hydrolysis gave the corresponding syn -α-hydroxy-β-amino acids, the N-terminal components of microginins 612, 646 and 680, in good yield. An analogous strategy for elaboration of the enantiopure anti -α-hydroxy-β-amino esters facilitated the asymmetric synthesis of the corresponding C(2)-epimeric α-hydroxy-β-amino acids. [ABSTRACT FROM AUTHOR]

Site-specific labeling is an important methodology to elucidate the biological function of a target protein. Here, we report a strategy for site-specific chemical labeling, termed the “on-site reaction”. We designed and readily synthesized a bifunctional ligand possessing two reaction sites, an enone and an azide moiety. This strategy involves an on-site conjugate addition reaction with protein followed by a Hüisgen cycloaddition reaction. We demonstrate this strategy by using fluorescein as a probe and peroxisome proliferator activated receptor γ (PPARγ) as a target protein. The reactions were evaluated by ESI-mass analysis and the binding site and modes of binding were revealed by X-ray crystallization analysis. The proposed methodology can easily convert a covalent ligand into chemical tool for protein functional analysis and the identification of drug targets. [ABSTRACT FROM AUTHOR]

An asymmetric conjugate addition of thiocarboxylic acids to in situ-generated ortho-quinomethanes ( o-QMs) catalyzed by bifunctional squaramide catalysts has been developed. The transformation proceeds with high yields (up to 96%) and enantioselectivities (up to 96% ee) in the oil-water phases. The resulting thioester could be converted facilely into the chiral benzyl mercaptan in high yield without loss of enantioselectivity. The study also showed that the oil-water biphase contributed significantly to the efficiency of the catalytic system. [ABSTRACT FROM AUTHOR]

The asymmetric sequential double Michael reactions of γ , δ -unsaturated β -ketoesters and nitroolefins catalyzed by 2 mol% of readily prepared Ni(II)-bis[( R , R )- N , N ′-dibenzylcyclohexane-1,2-diamine] complex and then with 1 equivalent of tetramethylguanidine (TMG) for cyclization have been developed. The reaction gave the corresponding Michael adducts of multifunctional cyclohexenol derivatives with three chiral stereocenters in good yields, moderate diastereoselectivities, and high enantioselectivities under mild reaction conditions. [ABSTRACT FROM AUTHOR]

2-Hydroxymethylpyridines undergo nickel-catalyzed hydrogenolysis upon activation with a chlorophosphate. Reactions employ diethylzinc and are proposed to proceed through secondary benzylzinc reagents. Quenching with deuteromethanol provides straightforward incorporation of a deuterium label in the benzylic position. Intramolecular conjugate additions with α,β-unsaturated esters are also demonstrated and support the intermediacy of a benzylzinc complex. [ABSTRACT FROM AUTHOR]

Exploratory studies on the sequential exo-mode oxacyclizations of acyclic polyene precursors have provided a substantial substructure of brevenal, including the fused tricyclic polyether with stereochemical patterns consistent with the AB and BC ring fusions. The synthesis of acyclic substrates featured two variations of Cr(II)/Ni(II) couplings for preparing 1,1-disubstituted allylic alcohols. A sequence of iodine-promoted cycloetherification, base-promoted intramolecular conjugate addition, and mercury-promoted cycloetherification produced the tricyclic substructure. [ABSTRACT FROM AUTHOR]

α,β-Unsaturated hydroxamates derived from the ‘chiral Weinreb amide’ auxiliary ( S )- N -1-(1′-naphthyl)ethyl- O - tert -butylhydroxylamine consistently adopt a defined conformation and undergo highly diastereoselective conjugate addition reactions with lithium amide reagents. The configuration of the N -1-(1′-naphthyl)ethyl group dictates the position of the O - tert -butyl group and also the configuration adopted by the pyramidal nitrogen atom via a ‘chiral relay’ effect. Conjugate addition of lithium amide reagents to these substrates proceeds on the face opposite to both the O - tert -butyl group and nitrogen lone-pair with high levels of diastereoselectivity. [ABSTRACT FROM AUTHOR]

A regio- and stereoselective thiocyanate addition to ynones is achieved using KSCN in AcOH at 70 °C. The reaction is extendable to ynals, ynesulfones, ynoic acids and ynoates. Adducts from ynones were readily transformed into thiazine-2-thione derivatives under slightly modified reaction conditions. In contrast, thiocyanated adducts from ynamides underwent an in situ decyanative amido cyclization towards isothiazolones. None of these events needed any transition metal or catalyst, attaining a high synthetic value. [ABSTRACT FROM AUTHOR]

Four novel paulomycin derivatives have been isolated from S. albus J1074 grown in MFE culture medium. These compounds are structural analogs of antibiotics 273a2α and 273a2β containing a thiazole moiety, probably originated through an intramolecular Michael addition. The novel, thiazole, moiety-containing paulomycins show a lower antibiotic activity than paulomycins A and B against Gram-positive bacteria. However, two of them show an improved activity against Gram-negative bacteria. In addition, the four novel compounds are more stable in culture than paulomycins A and B. Thus, the presence of an N-acetyl-L-cysteine moiety linked to the carbon atom of the paulic acid isothiocyanate moiety, via a thioester bond, and the subsequent intramolecular cyclization of the paulic acid to generate a thiazole heterocycle confer to paulomycins a higher structural stability that otherwise will conduce to paulomycin degradation and into inactive paulomenols. [ABSTRACT FROM AUTHOR]

A switchable enantioselectivity was achieved in a Cu-catalyzed asymmetric conjugate addition (ACA) reaction. The ethylene-bridged, hydroxyamide-functionalized NHC-AgI complex, readily accessible from a chiral β-amino alcohol, was found to be a versatile chiral ligand precursor for dual enantioselective control. The stereocontrol of the catalytic ACA reaction depended on the order of addition of the substrates. To a THF solution containing CuOTf (6 mol %), NHC-AgI complex ( 1b , R 1 = Et, R 2 = Bn, 4 mol %), and 2-cyclohexen-1-one ( 3 ) was added Et 2 Zn to yield ( R )-3-ethylcyclohexanone (( R )- 4 ) in 74% enantioselectivity (method A). In stark contrast, when 3 was added as a last component to a mixture of CuOTf (4 mol %), 1b (10 mol %), and Et 2 Zn in THF (method B), the ACA reaction afforded ( S )- 4 with 87% ee. In order to obtain an insight into various aspects of the present ACA reaction, the chiral NHC ligand precursors, substrates, and NHC skeletons were fully evaluated. A study of the relationship between the catalyst ee (ee cat ) and the product ee (ee pro ) revealed a chiral amplification phenomenon. Moreover, it was found that the ACA reaction using method A was not affected by the halide ion on the NHC-AgX complex, whereas the halide ion on the silver complex showed a significant influence on the enantiocontrol of the ACA reaction using method B. In particular, a Cu/NHC/I catalytic ratio of 1/1/2 was needed for a successful ACA reaction using method B. According to these factors affecting the reversal of enantioselectivity in the ACA reaction, a possible reaction pathway was proposed. [ABSTRACT FROM AUTHOR]

Copper-catalyzed asymmetric conjugate addition of alkylzirconium species to α,β-unsaturated thioesters is reported. A variety of functionalized alkyl nucleophiles were introduced with yields around 70% and ee's over 92%. The method was applied to the straightforward syntheses of the commercially important fragrances phenoxanol (both enantiomers 97% ee), and hydroxycitronellal (98% ee). The 1,4-addition products can be converted to enantiomerically enriched linear building blocks bearing a terminal functional group. Formation of further α,β-unsaturated thioesters provides an iterative route for the stereocontrolled synthesis of functionalized acyclic arrays and we demonstrate almost complete catalyst control in the formation of additional stereocentres. [ABSTRACT FROM AUTHOR]

A transition-metal-free method for the construction of functionalized quinolines from readily available acetophenones and anthranils is reported. This one-pot reaction cascade involves in situ generation of α,β-unsaturated ketones from the acetophenone via one-carbon homologation by DMSO followed by the aza-Michael addition of anthranils and subsequent annulation. DMSO acted in this reaction not only as solvent but also as one carbon source, thus providing a highly atom-economical and environmentally benign approach for the synthesis of 3-substituted quinolines. [ABSTRACT FROM AUTHOR]

The organocatalytic enantioselective conjugate reaction of 2-fluoro-1,3-diketones to nitroalkenes promoted by chiral binaphthyl-modified squaramide has been achieved. Treatment of 2-fluoro-1,3-diketones with nitroalkenes under mild reaction conditions afforded the corresponding Michael products containing fluorinated quaternary carbon stereocenter with excellent enantioselectivity (up to 98% ee). [ABSTRACT FROM AUTHOR]

A catalytic enantioselective construction of vicinal stereocenters is reported. The reaction takes advantage of thiourea-catalyzed intramolecular nitronate addition onto α,β-unsaturated ester to afford exceptional levels of enantioselectivity (up to 97 % ee) with moderate diastereoselectivity (up to 4:1). Using this method, a cross-conjugated ester was synthesized in few steps, from which a 6- endo- trig cyclisation led to the formation of all required functionalities for total syntheses of ergot alkaloids. The strategy not only offers first total syntheses of ergot alkaloids, festuclavine ( 1 c), and pyroclavine ( 1 e), and but also an efficient and general approach to other congeners such as, lysergol ( 1 b), and isolysergol ( 1 d). [ABSTRACT FROM AUTHOR]

A chiral-amine-catalyzed enantioselective and diastereodivergent method for aldehyde addition to electron-deficient olefins is presented. Hydrogen bonding was used as a control element to achieve unusual anti selectivity, which was further elucidated through mechanistic and computational studies. [ABSTRACT FROM AUTHOR]

Conjugate addition reactions of 2,4-pentandione, dibenzoylmethane and ethylacetoacetate to enones have been investigated using Amberlyst-15 or Amberlyst-15-DMAP acetate system as catalysts. When 2,4-pentandione reactions were carried out in the presence of Amberlyst-15, conjugate addition and/or conjugate-addition initiated ring closure products were obtained depending on the reaction conditions. However, unlike 2,4-pentandione, dibenzoylmethane gave only conjugate addition products with Amberlyst-15. When Amberlyst-15-DMAP acetate system was used, always only conjugate addition products were obtained with β-dicarbonyl compounds independent of the reaction conditions. [ABSTRACT FROM AUTHOR]

A two-step reaction sequence is described for the asymmetric formal α-propargylation of ketones. This approach takes advantage of an aminocatalyzed conjugate addition of ketones to alkylidene isoxazol-5-ones, followed by a controlled nitrosative degradation event. The target compounds can be accessed in broad scope, in moderate to good yields, perfect diastereocontrol and good to excellent enantioselectivity. [ABSTRACT FROM AUTHOR]

A simple and efficient protocol to access diarylmethyl thioethers through the triflic acid catalyzed vinylogous Michael addition of aromatic and aliphatic thiols to p-quinone methides under continuous-flow conditions by using a microreactor was developed. [ABSTRACT FROM AUTHOR]

A concise stereoselective synthesis of proposed dehydroindolizidine-alkaloids of types 179 and 207E1 was accomplished via Michael-type conjugate addition. A comparison of natural 207E and synthesised compound 207E on GC-FTIR revealed the double bond of natural 207E is most likely at the 7,8-position. [ABSTRACT FROM AUTHOR]

An unprecedented catalytic asymmetric reaction between azlactones and N-itaconimides has been developed. In the presence of an L-tert-leucine-based urea-tertiary amine Brønsted base catalyst, the tandem conjugate addition-protonation products could be attained in moderate yields with excellent enantio- and diastereoselectivities (up to 99% ee and >20:1 dr). The method provides an efficient approach to access valuable chiral ?-tertiary amine substituted succinimides containing nonadjacent stereocenters. [ABSTRACT FROM AUTHOR]

Peptides of the type H-Pro-Pro-Xaa-NH2 were evaluated as catalysts for conjugate addition reactions of acetophenones to cyanoolefins. Tripeptide H-D-Pro-Pro-Glu-NH2 with a carboxylic acid moiety in the side chain of Xaa was identified as a catalyst that provides γ,γ- dicyanoacetophenones in yields of up to 90% and stereoselectivies of up to 88:12 er. [ABSTRACT FROM AUTHOR]

The catalytic promiscuity of a ferulic acid decarboxylase from Enterobacter sp. (FDC_ Es) and phenolic acid decarboxylases (PADs) for the asymmetric conjugate addition of water across the C=C bond of hydroxystyrenes was extended to the N-, C- and S-nucleophiles methoxyamine, cyanide and propanethiol to furnish the corresponding addition products in up to 91% ee. The products obtained from the biotransformation employing the most suitable enzyme/nucleophile pairs were isolated and characterized after optimizing the reaction conditions. Finally, a mechanistic rationale supported by quantum mechanical calculations for the highly ( S)-selective addition of cyanide is proposed. [ABSTRACT FROM AUTHOR]

The synthesis of tri- and tetrasubstituted cyclopropanes from 3-aryl-substituted levoglucosenones (LGO) has been developed. In contrast to the unstabilised ylide dimethylsulfonium methylide which gives epoxides from LGO via 1,2-addition, we have found that the soft nucleophile dimethylsulfoxonium methylide affords cyclopropanes in moderate yields from LGO and in excellent yields and stereoselectivity with 3-aryl LGO derivatives. The use of 1,1,3,3-tetramethylguanidine as base in DMSO to generate the ylide provided the best yields and shortest reaction times. Ester stabilised sulfonium ylides could also be used to generate tetrasubstituted cyclopropane derivatives. One of the products was converted into a cyclopropyl lactone via Baeyer-Villiger oxidation to demonstrate the utility of applying cyclopropanation chemistry to LGO. [ABSTRACT FROM AUTHOR]

Herein we report the first example of an isoDGR-drug conjugate ( 2), designed to release paclitaxel selectively within cancer cells expressing integrin αVβ3. Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val-Ala dipeptide linker. Conjugate 2 displayed a low nanomolar affinity for the purified integrin αVβ3 receptor (IC50=11.0 n m). The tumor targeting ability of conjugate 2 was assessed in vitro in anti-proliferative assays on two isogenic cancer cell lines characterized by different integrin αVβ3 expression: human glioblastoma U87 (αVβ3+) and U87 β3-KO (αVβ3−). The isoDGR-PTX conjugate 2 displayed a remarkable targeting index (TI=9.9), especially when compared to the strictly related RGD-PTX conjugate 4 (TI=2.4). [ABSTRACT FROM AUTHOR]

The asymmetric conjugate addition of carbon and heteroatom nucleophiles to nitroalkenes is a very interesting tool for the construction of highly functionalized synthetic building blocks. Thanks to the rapid development of asymmetric organocatalysis, significant progress has been made during the last years in achieving efficiently this process, concerning chiral organocatalysts, substrates and reaction conditions. This review surveys the advances in asymmetric organocatalytic conjugate addition reactions to α,β-unsaturated nitroalkenes developed between 2013 and early 2017. [ABSTRACT FROM AUTHOR]

An efficient synthetic approach to access (indol-3-yl)ethane-1,2-diamines with a protecting group at the indole N atom from readily available 3-(2-nitrovinyl)indoles is reported. This approach includes solvent-free conjugate addition of O-pivaloylhydroxylamines to 1-Boc-3-(2-nitrovinyl)indoles followed by mild reduction of the adducts. The obtained (indol-3-yl)ethane-1,2-diamines are convenient synthetic precursors for several classes of marine alkaloids. The first total synthesis of racemic topsentin C, a secondary metabolite from Hexadella sp., based on this approach is reported. The initially proposed structure for topsentin C has been revised. [ABSTRACT FROM AUTHOR]

Sequential addition/annulation reactions of sulfinate and nitrite anions to β-(2-aminophenyl)-α,β-ynones led to valuable 4-sulfonylquinolines and 4-nitroquinolines. The latter proved to be versatile precursors of N-unsubstituted 4-aminoquinolines and 4-quinolones. Reaction of β-(2-aminophenyl)-α,β-ynones with DMF/NaOH resulted in the formation of 4-(dimethylamino)quinolines. The use of an alternative CO-free procedure for the preparation of substrates β-(2-aminophenyl)-α,β-ynones allowed extension of the methodology to the synthesis of 4-substituted 2-alkylquinolines. [ABSTRACT FROM AUTHOR]

Conjugate addition of carbon nucleophiles to electron-deficient olefins is one of the most powerful methods for forming carbon-carbon bonds. Despite great achievements in controlling the selectivity, variation of the carbon nucleophiles remains largely underexplored, with this approach relying mostly on organometallic reagents. Herein, we report that naturally abundant carbonyls can act as latent carbon nucleophiles for conjugate additions through a ruthenium-catalyzed process, with water and nitrogen as innocuous byproducts. The key to our success is homogeneous ruthenium(II) catalysis, combined with phosphines as spectator ligands and hydrazine as the reducing agent. This chemistry allows the incorporation of highly functionalized alkyl fragments into a vast array of electron-deficient olefins under mild reaction conditions in a reaction complementary to the classical organometallic-reagent-based conjugate additions mediated or catalyzed by 'soft' transition metals. [ABSTRACT FROM AUTHOR]

A new fluorescence probe (PML) for sensing HSO3− was developed based on a Michael addition reaction mechanism. The probe was composed of carbazole and 2-(3-cyano-4,5,5-trimethylfuran-2(5H)-ylidene)malononitrile moieties and can be easily synthesized. The carbazole-based probe can selectively detect HSO3− and shows good sensitivity with the limit of detection of 2.08 × 10−6 M in a PBS : DMF = 1 : 1 buffer solution. Upon addition of HSO3−, the intense fluorescence of the probe was quenched, and the color markedly changed from red to colorless. In addition, the probe can be used to detect HSO3− in dry white wine. [ABSTRACT FROM AUTHOR]