Arylation of β,γ-unsaturated lactones by a Heck-Matsuda reaction: an unexpected route to aryldiazene butenolides and pyridazinones

The palladium catalysed coupling of aryldiazonium salts with β-γ-unsaturated lactones under basic conditions has been investigated. Both (3H)-furanone and α-angelicalactone were evaluated as substrates in the Heck Matsuda reaction but both failed to afford the desired arylated butenolides. Under basic conditions, β-γ-unsaturated lactones generate highly nucleophilic enolates that preferentially undergo azo coupling reactions with arenediazonium salts to afford aryldiazene butenolides. The electronic and steric effect of the substituents on the aryldiazonium salt in the azo coupling reaction is described. Aryldiazene-lactone derivatives were obtained in good yields from a highly facile and straightforward procedure. An aminoisomaleimide was formed from (3H)-furanone and cyclised to the corresponding pyridazinones in modest yield.

Development and Validation of a Mice liar Electrokinetic Chromatography Method for Quantitative Determination of Butenolides in Piper malacophyllum (C. Presl) C. DC.

Introduction - A large number of natural and synthetic compounds having butenolides as a core unit have been described and many of them display a wide range of biological activities. Butenolides from P. malacophyllum have presented potential antifungal activities but no specific, fast, and precise method has been developed for their determination. Objective - To develop a methodology based on micellar electrokinetic chromatography to determine butenolides in Piper species. Methodology - The extracts were analysed in an uncoated fused-silica capillaries and for the micellar system 20 mmol/L SDS, 20% (v/v) acetonitrile (ACN) and 10 mmol/L STB aqueous buffer at pH 9.2 were used. The method was validated for precision, linearity, limit of detection (LOD) and limit of quantitation (LOQ) and the standard deviations were determined from the standard errors estimated by the regression line. Results - A micellar electrokinetic chromatography (MEKC) method for determination of butenolides in extracts gave full resolution for 1 and 2. The analytical curve in the range 10.0-50.0 mu g/mL (r(2) = 0.999) provided LOD and LOQ for 1 and 2 of 2.1/6.3 and 1.1/3.5 mu g/mL, respectively. The RSD for migration times were 0.12 and 1.0% for peak area ratios with 100.0 +/- 1.4% of recovery. Conclusions - A novel high-performance MEKC method developed for the analysis of butenolides 1 and 2 in leaf extracts of P. malacophyllum allowed their quantitative determined within an analysis time shorter than 5 min and the results indicated CE to be a feasible analytical technique for the quantitative determination of butenolides in Piper extracts. Copyright (C) 2010 John Wiley & Sons, Ltd.

Gymnoascolides A-C: Aromatic butenolides from an Australian isolate of the soil ascomycete Gymnoascus reessii

Three new aromatic butenolides, gymnoascolides A-C (1-3), have been isolated from the Australian soil ascomycete Gymnoascus reessii and assigned structures on the basis of detailed spectroscopic analysis. The absolute configurations of gymnoascolides B (2) and C (3) at C-5 were solved using a combination of chemical derivatization and quantum chemical simulations.

Estratégias para a síntese de γ-alquilidenobutenolídeos

α,β-unsaturated lactones possessing an alkylidene appendage group at the γ-position, are frequently termed γ-alkylidenebutenolides. Over the past decades, an increasing number of these compounds have been isolated from various natural sources. Members of this class of substances vary greatly in structural complexity and functionality. Besides that, many of them have been shown to display a wide range of biological activities. The γ-alkylidenebutenolides has attracted the attention of the organic synthetic chemists resulting in the development of a variety of process to synthesize them. This article review is concerned with the different approaches that can be utilized to prepare γ-alkylidenebutenolides.

Aplicações sintéticas do ácido mucobrômico e da 3,4-dibromofuran-2(5H)-ona

This review describes the use of two biomass-derivate butenolides as intermediates in organic synthesis, mucobromic acid and its reduced derivative 3,4-dibromofuran-2(5H)-one. The ambiphilic and ambident character of such butenolides make them versatile starting materials in the synthesis of natural and/or bioactive compounds. Thus, the reactions of mucobromic acid with C-nucleophiles and heteronucleophiles are described, as well as the nucleophilic addition to carbonyl reactions of 3,4-dibromofuran-2(5H)-one. Besides, both compounds are active in diverse metal cross-coupling reactions, manly with palladium in Suzuki and Sonogashira reactions.

Synthesis of a 7-Membered Biaryl Guanidine Catalyst and its Use in the Vinylogous Aldol Reaction

The present thesis outlines the preparation of a 7-membered guanidine. Initial efforts to obtain this guanidine via 2-chloro-1,3-dimethylimidazolinium chloride induced ring forming chemistry failed to provide the target in a reproducible fashion. Changing strategies, we were able to obtain the desired guanidine through CuCl mediated amination of a 7-membered thiourea intermediate to arrive at the target. In addition, the catalytic activity of this compound was evaluated in a vinylogous aldol reaction of dibromofuranone and four aromatic aldehydes to generate chiral γ-butenolides with modest to good enantiomeric excess. It was found that electron-poor aldehydes resulted in higher, 81% ee, whereas electron rich aldehydes led to low, 41% ee, levels of enantiomeric excess.

Studies on the Synthesis and Transformations of a Few 2(3H)- and 3(2H)-Furanones

The thesis entitled studies on the synthesis and transformations of a few 2(3H)- and 3(2H)- furanones. Furanones represent an interesting class of heterocyclic compounds, which constitute the central ring system of many natural products. The derivatives of furan is divided, depending on their structure 2(3H)-furanones(I), 2(5H)-furanones(II), and 3(2H)-furanones(III). Systems I&II are unsatured gama lactones known as ‘butenolides’. Compounds of this type also known as ‘crotonolactones’ based on the parent crotonic acid. In conclusion a number of 2(3H)-and 3(2H)- furanones were synthesized from dibenzoylalkene precursors and were characterized on the basis of spectral analytical and X-ray data. On direct irradiation 3,3-bis(4-chloropheneyl)-5-aryl-3H-furan -2-ones underwent decarbonylation to yield the corresponding alpha, beta- unsaturated carbonyl compounds and upon sensitized irradiation they underwent dimersation arising through a 2+2 cycloaddition reaction. Our studies on 3(2H)-furanones revealed that these compounds are thermally stable, while they undergo extensive decomposition to intractable mixtures under the influence of light. Similarly, the novel dibenzoylalkenes- type systems containing hetroatomatic rings synthesized by us also underwent extensive decomposition under the influence of heat. Some of the 3(2H)-furanones synthesized by us exhibit remarkable anti-proliferative activity.

Tellurium in organic synthesis: a general approach to buteno- and butanolides

The naturally occurring butanolides (-)-blastmycinolactol, (+)-blastmycinone, (-)-NFX-2, (+)-anti-mycinone as well as the four stereoisomers of the butenolide Acaterin were prepared in high enantiomeric purity using hydroxy-vinyl tellurides as starting materials. (C) 2012 Elsevier Ltd. All rights reserved.

A Facile, Versatile, and Mild Morita-Baylis-Hillman-Type Reaction for the Modular One-Pot Synthesis of Highly Functionalized MBH Adducts

MoritaBaylisHillman derivatives have been extensively investigated as intermediates in the preparation of important classes of compounds. However, there are intrinsic limitations regarding the structure of the Michael electrophile acceptors, the aldehydes, and the catalysts. Therefore, this transformation has several drawbacks, including, for example, its long reaction times. Herein we present a simple, general, fast, and high-yielding protocol for the one-pot synthesis of MoritaBaylisHillman derivatives. Our approach is driven by a lithium selenolate Michael/aldol operation with concomitant O-functionalization/selenoxide elimination cascade sequences.

New cassane butenolide hemiketal diterpenes from the marine creeper Caesalpinia honduc and their antiproliferative activity

Two new cassane butenolides, caesalpinolide A (1) and B (2), epimeric at the hemiketal position were isolated from the marine creeper Caesalpinia bonduc. The structures were elucidated by the analysis of spectroscopic data and relative stereochemistry was assigned on the basis of ROESY correlations. Compounds 1 and 2 were found to inhibit MCF-7 breast cancer cell lines with ICso values of (IlM)12.8 and 6.1, respectively, along with the inhibition of endometrial and cervical cancer cell lines

Cytotoxicity of 3,4-dihalogenated 2(5H)-furanones

Mucohalogen acids have been used for the preparation of a variety of 3,4-clihalogenated 2(5H)-furanones. In one synthetic step the carbarnates 2a-c and the pseudoanhydrides 4a-e were prepared using isocyanates and acid anhydrides. A series of 5-alkoxylated 3,4-dichloro-2(5H)-furanones 5a-o have been synthesized with a wide range of lipophilicity, using the hydroxy-form of mucohalogen acids 1a and 1b. The 5-allyl-3,4-dichloro-2(5H)-furanone 5f was derived into the dihydro-isoxazol 6 and the oxirane 7. The methyl ester 5a was converted with ammonia into the tetramic acid chloride 11. The pseudo acid chloride 3 was reacted further into the bis aziricline 8. Reduction of the mucochloric acid 1a furnished the trichlorofuranone 3. The cytotoxicity of these simple and bis-cyclic butenolides have been evaluated in tissue culture on MAC13 and MAC16 cancer cell lines using the MTT cytotoxicity assay. The ester 5g, the acetate 4b and the carbamate 2b displayed a cytotoxicity in the low micromolar range. Further, an IC50 (50% inhibitory concentration) of 50 nM and 30 nm was determined forthe epoxide 7 and the aziridine 18. © 2004 The Authors Recieved.

Synthesis and evaluation of 5-arylated 2(5H)-furanones and 2-arylated pyridazin-3(2H)-ones as anti-cancer agents

Bis-cyclic butenolides, 5-arylated 2(5H)-furanones 6a-c, 7a, b and the 3(2H)-pyridazones 9a-d were prepared by using the aldehyde form of muco halogen acids in electrophilic substitution reactions and in an aldol-like condensation reaction. The cytotoxicity of these simple and bis-cyclic butenolides have been evaluated in tissue culture studies on MAC 13 and MAC 16 murine colon cancer cell lines. The butyl furanone 3 displayed the highest cytotoxicity of 3 μM, as one selected example of a series of dichlorinated pseudoesters. The 5-arylated 2(5H)-furanones 6 and 7 did not show a structure-activity relationship (SAR) depending on the substitution pattern of the aromatic system. An IC50 (concentration inhibiting growth by 50%) was found within a range of 30-50 and 40-50 μM for the MAC 13 and MAC 16 cell lines, respectively. The pyridazine series 9 showed a maximum in-vitro activity for the p-methoxydrivative 9b, having an IC50 of 17 in MAC 13 and 11 μM in MAC 16 cell lines. Selected examples of each series and further novel 2(5H)-furanones such as the hydrazone 5 and the hydantoin 8 have been screened in-vivo in mice and the data are presented. For the pyridazines 9a-d, the in-vitro cytotoxicity correlated with an in-vivo inhibition of tumour growth. The ring expansion of the 5-membered 2(5H)-furanone ring system such as 6a into the 6-membered 3(2H)-pyridazone 9b led to an agent with improved antineoplastic properties. On the resistant MAC 16 cell line the pyridazone 9b displayed 52% tumour inhibition in mice at a dose of 50 mg kg-1 compared with 27% for the 5-FU standard.