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Despite the great potential of biorenewable α-methylene-γ-butyrolactone (MBL) to produce functional, recyclable polyester, the ring-opening polymerization (ROP) of MBL remains a challenge due to th...

High-density poly(α-methylene-γ-butyrolactone) (PMBL) brushes were produced by surface-initiated atom transfer radical polymerization of α-methylene-γ-butyrolactone (MBL), a biomass derived from tulips, on a silicon substrate. The relative elastic modulus was evaluated through force-curve measurements using a scanning force microscopy. The friction coefficient was measured using a macroscopic friction test. The PMBL brushes exhibit larger elastic modulus and better friction resistance than PMMA brushes as a result of the highly stretched conformation and polar interaction between PMBL chains.

It is an effective strategy to tailor material properties by copolymerization of monomers with different chemical structures and to adjust the compositions and sequence distributions of resultant c...

The catalytic asymmetric ene-type reactions of vinylogous hydrazone were accomplished by using chiral N,N'-dioxide-metal salt complexes as catalysts. A wide range of electrophiles, including isatins, α-ketoester, imines, and aldehydes reacted with (E)-2-methyl-N-(piperidin-1-yl)prop-2-en-1-imine efficiently, affording the corresponding homoallylic alcohols and amines in high yields (up to 99%) with excellent ee values (up to 99%). The methodology provided a convenient way to synthesize bioactive chiral α-methylene-γ-butyrolactone derivatives.

A regio- and stereoselective one-pot C-H insertion/olefination protocol has been developed for the late stage installation of α-methylene-γ-butyrolactones into conformationally restricted cyclohexanol-derivatives. The method has been successfully applied in the total synthesis of eudesmanolide natural product frameworks, including α-cyclocostunolide.

This work reports the synthesis and characterization of new ferrocene derivatives functionalized with one or two α-methylene-γ-butyrolactone rings. These compounds were prepared via Reformatsky-type reaction between carbonyl ferrocene derivatives and ethyl 2-bromomethylacrylate in 33–85% yields.

Construction of spirocyclic pyrrolidines bearing a spiro quaternary stereocenter is an enormous challenge in synthetic organic chemistry. In this report, we introduce a Ag(I)/CAAA-amidphos-catalyzed enantioselective 1,3-dipolar cycloaddition between azomethine ylides and &alpha, methylene-&gamma, butyrolactone as an effective strategy for the construction of excellent endo-selective spiro-[butyrolactone-pyrrolidine] derivatives. Meanwhile, the catalytic system was also successfully applied in the three-component one-pot reaction of azomethine ylides formed in situ under the action of N,N&prime, diisopropylcarbodiimide serving as a dehydrator. Under the optimal conditions, endo-pyrrolidine derivatives bearing a spiro quaternary stereocenter were obtained with high to excellent yields (up to 95% yield) and enantioselectivities (up to 93% ee).

A remarkably effective method allowing an extremely high enantioselective synthesis of the spiro-fused 2-oxindole/α-methylene-γ-butyrolactones is described. The key strategy lies in the use of indium-catalyzed asymmetric amide allylation of N-methyl isatin with functionalized allylstannanes, which can lead to the antineoplastic spirocyclic lactones in almost enantiopure forms.

6-Tuliposide A {6-O-(4-hydroxy-α-methylenebutyryl)-D-glucopyranose} was isolated from thunberg spiraea (Spiraea thunbergii) leaves. Acid-hydrolysis of this compound generated tulipalin A (α-methylene-γ-butyrolactone). This compound is thus considered as a precursor of insecticidal tulipalin A.

A regio- and stereoselective one-pot C–H insertion/olefination protocol has been developed for the late stage installation of α-methylene-γ-butyrolactones into conformationally restricted cyclohexanol-derivatives. The method has been successfully applied in the total synthesis of eudesmanolide natural product frameworks, including α-cyclocostunolide.

Design, synthesis, and evaluation of α-methylene-γ-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNFα-induced NF-κB activity, cancer cell growth and tumor growth in an ovarian cancer model. A second iteration of synthesis and screening identified 29 which inhibited cancer cell growth with low-μM potency. Our data suggest that an isatin-derived spirocyclic α-methylene-γ-butyrolactone is a suitable core for optimization to identify novel anticancer agents.

In consideration of the fact that the α-methylene-γ-butyrolactone moiety is a major bio-functional group in the structure of carabrone and possesses some agricultural biological activity, forty-six new ester and six new ether derivatives containing α-methylene-γ-butyrolactone moieties were synthesized, and their fungicidal activities against Colletotrichum lagenarium and Botrytis cinerea were investigated. Most of the synthesized compounds showed moderate to significant fungicidal activity. Among them, halogen atom-containing derivatives showed better activity than others, especially compounds 6a,d which exhibited excellent fungicidal activity against C. lagenarium, with IC50 values of 7.68 and 8.17 μM. The structure-activity relationship (SAR) analysis indicated that ester derivatives with electron-withdrawing groups on the benzene ring showed better fungicidal activity than those with electron-donating groups. A quantitative structure-activity relationship (QSAR) model (R2 = 0.9824, F = 203.01, S2 = 0.0083) was obtained through the heuristic method. The built model revealed a strong correlation of fungicidal activity against C. lagenarium with the molecular structures of these compounds. These results are expected to prove helpful in the design and exploration of low toxicity and high efficiency α-methylene-γ-butyrolactone-based fungicides.

Allergic contact dermatitis due to plants is common. Potentially allergenic plants and plant products are found in many everyday environments, such as the home, the garden, the workplace, and recreational settings. By improving our knowledge of allergenic plant-derived chemical compounds, we will be better positioned to identify novel allergens. We review the most relevant chemical allergens that contribute to plant allergic contact dermatitis and propose a clinical classification system based on 5 major families of chemical sensitizers: α-methylene-γ-butyrolactones, quinones, phenol derivatives, terpenes, and miscellaneous structures (disulfides, isothiocyanates, and polyacetylenic derivates). We also describe the different clinical pictures of plant allergic contact dermatitis and review currently available patch test materials. A better understanding of the specific allergens involved in plant allergic contact dermatitis will help to predict cross-reactivity between different plant species or families.

A novel and efficient synthetic route to the anti-cancer natural product yomogin has been developed using a Telescoped Intramolecular Michael-Olefination (TIMO) sequence as the key step. Two variants of the TIMO sequence have been used successfully: a two-step acylation approach using diethyl phosphonoacetic acid and a base-free variant using triphenylphosphoranylideneketene (Bestmann’s ylide). The natural product, 3-oxodiplophyllin, was also prepared en route to yomogin.

The binding of low-molecular-weight compounds to nucleophilic side-chains of amino acids bound within a protein, resulting in a hapten-modified macromolecule, is discussed to represent the very first step within the development of allergic contact dermatitis. For one of the best-known occupational dermatoses in the field of plant breeding, the so-called tulip fingers, α-methylene-γ-butyrolactone (tulipalin A) was proved to be the causative agent. In this paper, the reaction of tulipalin A with Nα-hippuryl-L-lysine as a model for peptide-bound lysine was studied. After the incubation of the α-methylene-γ-butyrolactone with the dipeptide in varying molar ratios in methanolic solution at 37°C up to 3 weeks, the reaction was monitored using reversed-phase high-performance liquid chromatography with UV detection. Tulipalin A was found to react with the Ε-amino group, resulting in the formation of one characteristic reaction product. After isolation, the structure of this addition product was unambiguously characterised by nuclear magnetic resonance spectroscopy as 2-(2-benzoylamino-acetylamino)-6-[(2-oxo-tetrahydro-furan-3-ylmethyl)amino] hexanoic acid (Hip-LysTu). After incubation of bovine serum albumin with tulipalin A, followed by acid hydrolysis and amino acid analysis, LysTu was found as addition product, thus representing the first known amino acid derivative resulting from the conjugation of the electrophilic α-methylene-γ-butyrolactone to protein.

A remarkably effective method allowing an extremely high enantioselective synthesis of the spiro-fused 2-oxindole/α-methylene-γ-butyrolactones is described. The key strategy lies in the use of indium-catalyzed asymmetric amide allylation of N-methyl isatin with functionalized allylstannanes, which can lead to the antineoplastic spirocyclic lactones in almost enantiopure forms.

An expedient access to almost enantiopure spiro compounds (III) and (V) via an unprecedented Cu-catalyzed 1,3-dipolar cycloaddition is developed.

We developed a facile method of enzyme-mediated conversion of 6-tuliposide to α-methylene-γ-butyrolactone (tulipalin). We used a tuliposide-converting enzyme for the conversion of 6-tuliposides extracted from tulip tissues into the corresponding tulipalins in high yields within 2 h at pH 7.0. The resulting tulipalins were selectively extracted by using several organic solvents.

The enantioselective allylation of aldehydes using a variety of β-amido functionalized allyltributylstannanes proceeded smoothly with good to high yields and enantioselectivities in the presence of 10 mol % of a chiral catalytic complex prepared from In(OTf) 3 and 2,6-bis[( S )-4-isopropyloxazolin-2-yl]pyridine {( S )- i -Pr-pybox}, providing the corresponding chiral γ-hydroxy amides.

Background: The Michael acceptor scaffolding is a source of rich biological activity for α-methylene-γ-butyrolactones and their derivatives. A wide variety of these structures are present in many natural products that are well-known for their useful medicinal properties. Results: The first example of a borylated α-methylene-γ-butyrolactone is presented herein, along with its antipancreatic cancer activities against Panc-1, MIA PaCa-2 and BXPC-3. The synthetic route chosen allows for a wide range of lactones to be synthesized through different cross-coupling reactions starting from arylic bromide precursors. The precursors were synthesized by way of a highly efficient, chemoselective and indium-promoted Barbier reaction. Specifically, the indium metal reacted with only one of two present bromide functionalities: an allylic bromide in the presence of an arylic one. The bromide precursors were also tested for activity in the same bioassay as the borylated lactone and parthenolide. Conclusion: Notably, these brominated compounds demonstrate a significantly higher level of activity than parthenolide.

Copolymers of halogenated styrenes and α-methylene-γ-butyrolactone were synthesized in bulk via free radical initiation. The polymerizations, in most cases, proceeded rapidly to high conversion. The high conversions obtained necessitated the use of high conversion methods to calculate reactivity ratios. In all the copolymerizations the α-methylene-γ-butyrolactone proved to be the more reactive monomer.

Substituted dihydrobenzofurans and tetrahydrochromans have been prepared from respectively α-methylene-γ-butyrolactone and δ-valerolactone via a 1,3-Michael-Claisen reaction from two 3-carbon units, 1,1-bis-(methylthio)-2-propanone or butanone, and an α-methylene lactone.

A zinc or indium-mediated Barbier-type allylation of aldehydes with 3-bromomethyl-5H-furan-2-one in aqueous solvents was developed to provide an efficient route to α-methylene-γ-butyrolactone, which is synthetically very useful. The desired products were obtained in moderate to high yields in aqueous solvents. Excellent drs were achieved, among which the best diastereomeric ratios of products were found when water was used in the indium-mediated reaction, and THF–NH4Cl (sat, aq) (2:1) mixture in the zinc-mediated reaction. Furthermore, the allylation can be induced by chiral centers, especially those in the α-position, as a substrate-controlled reaction to obtain the enantioselective homoallylation alcohols.

In a search for inhibitors of platelet aggregation, some alpha-methylene-gamma-butyrolactones bearing 2-methylquinoline and 8-hydroxyquinoline moieties were synthesized and evaluated for antiplatelet activities against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating factor (PAF)-induced aggregation in washed rabbit platelets. With the exception of 2-[[2,3,4,5-tetrahydro-4-methylene-5-oxo-2-(4-phenylphenyl)-2 -furanyl]methoxy]-8-hydroxyquinoline (8f), these alpha-methylene-gamma-butyrolactones completely inhibited the platelet aggregation induced by AA and Col. The 2-methylquinoline derivatives were also active against Thr- and PAF-induced aggregation, while their 8-hydroxyquinoline counterparts were relatively inactive.

[reaction: see text] The palladium-catalyzed arylation of the alpha-methylene-gamma-butyrolactone proceeds in good yields and may be directed toward the synthesis of 3-benzylfuran-2(5H)-ones when the starting aryl iodides contain strongly electron-withdrawing groups. The combined palladium-catalyzed arylation/hydrogenation of the alpha-methylene-gamma-butyrolactone represents a new simple entry into functionalized alpha-benzyl-gamma-butyrolactones.

The amount of research activity concerning alpha-methylene-gamma-butyrolactones and alpha-alkylidene-gamma-butyrolactones has increased dramatically in recent years. This Review summarizes the structural types, biological activities, and biosynthesis of these compounds, concentrating on publications from the past 10 years. Traditional approaches to alpha-methylene-gamma-butyrolactones and alpha-alkylidene-gamma-butyrolactones are then reviewed together with novel approaches, including those from our own research group, reported more recently.

Binary copolymers of 2- and 3-vinyl thiophene were synthesized via freeradical initiated bulk polymerization. The copolymerizations proceeded readily at 65°C to yield copolymers of reasonable molecular weight. The 2-vinyl thiophene monomer was found to be more reactive than the α-methylene-γ-butyrolactone, while the 3-vinyl thiophene was found to be less reactive than the lactone.

[reaction: see text] Olefin cross-metathesis between alpha-methylene-gamma-butyrolactone and terminal olefins is described. Moderate to excellent yields of alpha-alkylidene-gamma-butyrolactones were obtained with high E-stereoselectivity in the presence of low catalyst loading in refluxing CH2Cl2. In addition, the use of various additives was found to have a dramatic effect on the efficiency of the cross-metathesis (CM) process by circumventing the formation of the isomerized byproduct.

The reaction between dimethyl acetylenedicarboxylate and various phenols including phenol, 1-naphthol, 2-naphthol, 8-hydroxyquinoline, 1,6-dihydroxynaphthalene, cathechol, hydroquinone and resorcinol in the presence of catalytic amounts of pyridine leads to fused α-methylene-γ-butyrolactone derivatives in good yields.

An efficient, high-yielding route to β-methyl-α-methylene-γ-butyrolactone (βMMBL)—a monomer for the production of high-performance engineering bioplastics—from biorenewable and inexpensive itaconic acid has been developed. The monomer prepared by this new route is of high purity as isolated without purification, as evidenced by NMR as well as small and large-scale polymerization tests.

[reaction: see text] The palladium-catalyzed arylation of the alpha-methylene-gamma-butyrolactone proceeds in good yields and may be directed toward the synthesis of 3-benzylfuran-2(5H)-ones when the starting aryl iodides contain strongly electron-withdrawing groups. The combined palladium-catalyzed arylation/hydrogenation of the alpha-methylene-gamma-butyrolactone represents a new simple entry into functionalized alpha-benzyl-gamma-butyrolactones.

An expedient access to optically active spiro-[butyrolactone-pyrrolidine] was successfully developed via an unprecedented Cu(I)-catalyzed exo-selective 1,3-DC of azomethine ylides with α-methylene-γ-butyrolactone, which exhibited high diastereoselectivity (>98 : 2), excellent enantioselectivity (96–>99% ee) and a broad substrate scope under mild conditions.

A zinc or indium-mediated Barbier-type allylation of aldehydes with 3-bromomethyl-5H-furan-2-one in aqueous solvents was developed to provide an efficient route to α-methylene-γ-butyrolactone, which is synthetically very useful. The desired products were obtained in moderate to high yields in aqueous solvents. Excellent drs were achieved, among which the best diastereomeric ratios of products were found when water was used in the indium-mediated reaction, and THF-NH(4)Cl (sat, aq) (2 : 1) mixture in the zinc-mediated reaction. Furthermore, the allylation can be induced by chiral centers, especially those in the α-position, as a substrate-controlled reaction to obtain the enantioselective homoallylation alcohols.

(Z)-β-Bromoallylsilanes (1a-c) were prepared by a stereoselective Ni-catalyzed cross-coupling reaction of 1,1-dibromo-4-phenylbutene (4) with silylmethylmagnesium halide. Sakurai-Hosomi reaction of la with aldehyde gave syn-3-alkyl-2-bromo-4-hydroxyalkene (2a, 2c, and 2e) and that with acetal gave syn-4-alkoxy-3-alkyl-2-bromoalkene (2b and 2d) stereoselectively. The products with formyl function reacted with a Ni-carbonyl complex to give β,γ-disubstituted α-methylene-γ-butyrolactones (3) in good yields. Pd-catalyzed cross-coupling reaction of la-c or 4 with silylmethylmagnesium halide gave 1,1-bis(silylmethyl)-1-alkenes (1d-i), which reacted with dimethyl acetal to generate more functionalized allylsilane (6).

The palladium-catalysed arylation/vinylation of α-methylene-γ-butyrolactone (1) proceeds in good yield, mainly to give stereodefined aryl/vinyl-substituted α-alkylidene-γ-butyrolactones 4. In addition, the palladium-catalysed arylation of α-methylene-γ-butyrolactone (1) may be directed towards the synthesis of 3-benzylfuran-2(5H)-ones 3 when the starting aryl iodides contain groups with electron-withdrawing conjugative properties. The combined palladium-catalysed coupling/hydrogenation reactions represent a new, simple route to functionalised 3-alkyl-γ-butyrolactones 5, giving prominence to the possibility of stereocontrol in the formation of the new stereocentres.

Contact allergy from handling alstroemeria (Alstroemeria) has been widely observed in horticulturalists and florists (1–5). α-methylene-γ-butyrolactone (α-MBL) has been shown to be the causative agent (6, 7). In the present study, delayed-type contact dermatitis due to alstroemeria was evaluated using the guinea pig maximization test (GMT) (8), and the intensity of allergic reactions was investigated by quantifying the contents of α-MBL in different parts of alstroemeria by high-performance liquid chromatography (HPLC) (9).

14C-labelled γ, γ-dimethyl-α-methylene-γ-butyrolactone 1 and 1-oxa-Spiro [4.5]-3-methylene-2-decanone 2 have been synthesized from acetone and cyclohexanone respectively and 14C-labelled ethyl bromomethacrylate (Reformatsky reaction). The synthesis of this last compound is also described.

The kinetics of α-methylene-γ-butyrolactone (α-MBL) homopolymerization was investigated in N,N-dimethylformamide (DMF) with azobis(isobutyronitrile) as initiator. The rate of polymerization (Rp) was expresed by Rp = k[AIBN]0.54[α-MBL]1.1 and the overall activation energy was calculated as 76.1 kJ/mol. Kinetic constants for α-MBL polymerization were obtained as follows: kp/kt1/2 = 0.161 L1/2 mol−1/2·s−1/2; 2fkd = 2.18 × 10−5 s−1. The relative reactivity ratios of α-MBL(M2) copolymerization with styrene (r1 = 0.14, r2 = 0.87) were obtained. Applying the Q–e scheme led to Q = 2.2 and e = 0.65. These Q and e values for α-MBL are higher than those for MMA