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Phytohormones have significant roles in redox metabolism, inflammatory responses, and cellular survival mechanisms within the microenvironment of the mammalian brain. Herein, we identified the mammalian molecular targets of three representative strigolactone (SL) analogues structurally derived from apocarotenoids and the functional equivalent of plant hormones. All tested SL analogues have an inhibitory effect on NLRP3 inflammasome-mediated IL-1β release in murine microglial cells. However, IND and EGO10 became prominent among them due to their high potency at low micromolar doses. All SL analogues dose-dependently suppressed the release and expression of proinflammatory factors. For EGO10 and IND, IC50values for iNOS-associated NO secretion were as low as 1.72 and 1.02 μM, respectively. In silico analyses revealed that (S)-EGO10 interacted with iNOS, NLRP3, and Keap1 ligands with the highest binding affinities among all stereoisomeric SL analogues. Although all compounds were effective in microglial Mox phenotype polarization, 4-Br-debranone exhibited a differential pattern for upregulating Nrf2-driven downstream enzymes.

The reactivity of “furan-ynes” in combination with pyridine and quinoline N-oxides in the presence of a Au(I) catalyst, has been studied, enabling the synthesis of three different heterocyclic scaffolds. Selective access to two out of the three possible products, a dihydropyridinone and a furan enone, has been achieved through the fine-tuning of the reaction conditions. The reactions proceed smoothly at room temperature and open-air, and were further extended to a broad substrate scope, thus affording functionalized dihydropyridinones and pyranones.

A methodology for the total and modulable synthesis of (4Z)-lachnophyllum lactone (1), on a gram scale, is reported for the first time. The present work started with the design of a retrosynthetic pathway for the target compound, with the key step identified in Pd–Cu bimetallic cascade cross-coupling cyclization. (4Z)-Lachnophyllum lactone (1) is an acetylenic furanone previously isolated, in a low amount, from the organic extract of the autotrophic weedConyza bonariensis. Tested against the stem parasitic weed Cuscuta campestrisin a seedling growth bioassay, (4Z)-lachnophyllum lactone (1) showed almost 85% of inhibitory activity up to 0.3 mM in comparison with the control. At the same concentration, the compound displayed radicle growth inhibitory activity of the root parasitic weeds Orobanche minorand Phelipanche ramosahigher than 70 and 40%, respectively. Surprisingly, the compound showed a high percentage of inhibition, up to 0.1 mM, on C. bonariensisseed germination too. This versatile synthetic strategy was also used to obtain two further natural analogues, namely, (4E)-lachnophyllum lactone (8) and (4Z,8Z)-matricaria lactone (9), that showed, in most cases, the same inhibitory trend with slight differences, highlighting the importance of the stereochemistry and unsaturation of the side chain. Furthermore, all of the compounds showed antifungal activity at 1 mM reducing the mycelial growth of the olive pathogen Verticillium dahliae. The design and implementation of scalable and modulable total synthesis on a gram scale of acetylenic furanones allow the production of a large amount of these natural products, overcoming the limit imposed by isolation from natural sources. The results of the present study pave the way for the development of ecofriendly bioinspired pesticides with potential application in agrochemical practices as alternative to synthetic pesticides.

Background: Fungi are a well-known and valuable source of compounds of therapeutic relevance, in particular of novel anticancer compounds. Although seldom obtainable through isolation from the natural source, the total organic synthesis still remains one of the most efficient alternatives to resupply them. Furthermore, natural product total synthesis is a valuable tool not only for discovery of new complex biologically active compounds but also for the development of innovative methodologies in enantioselective organic synthesis. Methods: We undertook an in-depth literature searching by using chemical bibliographic databases (SciFinder, Reaxys) in order to have a comprehensive insight into the wide research field. The literature has been then screened, refining the obtained results by subject terms focused on both biological activity and innovative synthetic procedures. Results: The literature on fungal metabolites has been recently reviewed and these publications have been used as a base from which we consider the synthetic feasibility of the most promising compounds, in terms of anticancer properties and drug development. In this paper, compounds are classified according to their chemical structure. Conclusion: This review summarizes the anticancer potential of fungal metabolites, highlighting the role of total synthesis outlining the feasibility of innovative synthetic procedures that facilitate the development of fungal metabolites into drugs that may become a real future perspective. To our knowledge, this review is the first effort to deal with the total synthesis of these active fungi metabolites and demonstrates that total chemical synthesis is a fruitful means of yielding fungal derivatives as aided by recent technological and innovative advancements.

Background: Fungi are a well-known and valuable source of compounds of therapeutic relevance, in particular of novel anticancer compounds. Although seldom obtainable through isolation from the natural source, the total organic synthesis still remains one of the most efficient alternatives to resupply them. Furthermore, natural product total synthesis is a valuable tool not only for discovery of new complex biologically active compounds but also for the development of innovative methodologies in enantioselective organic synthesis. Methods: We undertook an in-depth literature searching by using chemical bibliographic databases (SciFinder, Reaxys) in order to have a comprehensive insight into the wide research field. The literature has been then screened, refining the obtained results by subject terms focused on both biological activity and innovative synthetic procedures. Results: The literature on fungal metabolites has been recently reviewed and these publications have been used as a base from which we consider the synthetic feasibility of the most promising compounds, in terms of anticancer properties and drug development. In this paper, compounds are classified according to their chemical structure. Conclusion: This review summarizes the anticancer potential of fungal metabolites, highlighting the role of total synthesis outlining the feasibility of innovative synthetic procedures that facilitate the development of fungal metabolites into drugs that may become a real future perspective. To our knowledge, this review is the first effort to deal with the total synthesis of these active fungi metabolites and demonstrates that total chemical synthesis is a fruitful means of yielding fungal derivatives as aided by recent technological and innovative advancements.

A mild and efficient telescoped procedure for the stereoselective alkenylation of simple, non-activated amides using LiCH2SiMe3and carbonyl compounds as surrogates of alkenyllithium reagents is reported. Our methodology relies on the formation of stable tetrahedral intermediates, which, upon collapse into highly reactive lithium enolates in a solvent-dependent fashion, allows for the assembly of α,β-unsaturated ketones in a single synthetic operation with high stereoselectivity.

Strigolactones (SLs) are new plant hormones with various developmental functions. They are also soil signaling chemicals that are required for establishing beneficial mycorrhizal plant/fungus symbiosis. In addition, SLs play an essential role in inducing seed germination in root-parasitic weeds, which are one of the seven most serious biological threats to food security. There are around 20 natural SLs that are produced by plants in very low quantities. Therefore, most of the knowledge on SL signal transduction and associated molecular events is based on the application of synthetic analogues. Stereochemistry plays a crucial role in the structure–activity relationship of SLs, as compounds with an unnatural D-ring configuration may induce biological effects that are unrelated to SLs. We have synthesized a series of strigolactone analogues, whose absolute configuration has been elucidated and related with their biological activity, thus confirming the high specificity of the response. Analogues bearing the R-configured butenolide moiety showed enhanced biological activity, which highlights the importance of this stereochemical motif.

Strigolactones (SLs) are a novel class of plant hormones. Previously, we found that analogs of SLs induce growth arrest and apoptosis in breast cancer cell lines. These compounds also inhibited the growth of breast cancer stem cell enriched-mammospheres with increased potency. Furthermore, strigolactone analogs inhibited growth and survival of colon, lung, prostate, melanoma, osteosarcoma and leukemia cancer cell lines. To further examine the anti-cancer activity of SLs in vivo, we have examined their effects on growth and viability of MDA-MB-231 tumor xenografts model either alone or in combination with paclitaxel. We show that strigolactone act as new anti-cancer agents in inhibition of breast cancer in xenograft model. In addition we show that SLs affect the integrity of the microtubule network and therefore may inhibit the migratory phenotype of the highly invasive breast cancer cell lines that were examined.

In this work we report the synthesis of new fluorescent analogues of strigolactones, their spectroscopic properties and the evaluation of their biological activity both on seeds of Orobanche aegyptiacaand on the AM fungus Gigaspora margarita. The synthesis has been accomplished according to two different synthetic plans and allows the introduction of various substituents on the A and C rings of the framework, thus enabling access to bioactive molecules with different spectroscopic properties.

The advice of professor Dieter Seebach “Thinking of polar organometallics compounds as carbanions is an impoverishment rather that a simplification” (ISCC, Durham 1984), perfectly fits the statement of professor Manfred Schlosser, who coined the term polar organometallic”, according which no difference in reactivity patterns of organometallic reagents can be rationalized without taking into account the metal counterion and its specific interactions with the accompanying carbon backbone. Both statements stress the need of considering the metal as a key component of these reagents, that can initiate and govern the subsequent reactions. The class of the socalled polar organometallics comprises the reagents of the most common alkali and alkaline earth metals and extend into the area of organozinc derivatives. All these reagents are characterized by a polar carbon-metal bond and the pattern of polarity vary significantly with the metal. Metalation is one of the widely used synthetic routes in order to obtain a labile and reactive carbon-metal bond from the relatively inert carbon-hydrogen bond. Until recently, alkyllithium reagents and bulky lithium amides have been commonly employed for this purpose. More recently, some groups have pioneered alternative metalating agents made up of two or more distinct compound types. Several examples include Schlossers superbases, Kondo and Uchiyamas 2,2,6,6-tetramethylpiperidide (TMP)-zincate complexes, and Knochels turbo-Grignard reagents. In this review, we wish to report the most recent contributions appeared in the literature from 2005 to date, concerning the use of polar organometallics in synthesis. The topic has been divided into three sections, the first of which deals with metalated 1,2-dienes and the second one with metalated 1,3-dienes (the metal is in turn lithium, potassium or magnesium). The third section is dedicated to miscellaneous applications that cannot be comprised into the previous classification.

Two steps is the rule: A concise synthesis of versatile α′‐methoxy‐γ‐pyrones (see scheme) is described that uses an innovative desymmetrization of α,α′‐dimethoxy‐γ‐pyrone, relying upon conjugate addition of nucleophiles. This new strategy is applied to the preparation of α‐methyl‐ and α‐carboxaldehyde‐α′‐methoxy‐γ‐pyrones and to a short synthesis of verticipyrone.

This review gives an overview of our recent developments in the chemistry of 1,3- and 1,2-butadiene derivatives, with a special attention to their use in palladium catalyzed reactions. The reactions of ,-unsaturated and propargylic acetals with various lithium and mixed lithium-potassium Schlosser reagents will be firstly reviewed. These processes have afforded (E)-1-alkoxy-1,3-dienes, and (E)-1,3-enynes, 1,3-diynes or allenes, respectively. When the reactions have been carried out in the presence of suitable electrophiles a linear route to functionalized derivatives has been set up. The above-mentioned compounds can be thus considered valuable synthetic tools for the construction of various and more complex structures and, in particular, they have been established to be useful reagents for the Suzuki-Miyaura cross-coupling reaction. As a matter of fact, alkoxy-functionalized butadienylboronic esters have been synthesized, cross-coupled with both N-protected and N-unprotected haloanilines (or halophenols), and finally transformed under mild conditions into quinolines and quinolinones (or chromenes and chromenones). The second part of the paper will deal with our recent interest in the Heck coupling of conjugate systems. In particular, the synthesis of -arylated ,-unsaturated carbonyl compounds, by regioselective Heck process on 1-alkoxy-1,3-dienes in ionic liquids will be reviewed, in conjunction with the Heck coupling of 1,2-dien-1-ols to -arylated ,-unsaturated aldehydes. A survey of the recent literature on closely related topics will complete the contribution.

The Nazarov reaction of pentadienyl cations generated by protonation of either dienones or alkoxytrienes has been examined in detail both experimentally and by DFT calculations. In particular, calculations at the B3LYP/6‐311G** level of theory accurately predicted, and accounted for, the outcome of the Brønsted acid catalyzed electrocyclization of 4π‐electron systems in which one of the double bonds involved in the process was embedded in N‐ and S‐heterocyclic rings. Calculations showed that both heteroatoms are capable of accelerating the ring closure by stabilizing the partial positive charge which develops at C‐6 (C‐2) in the transition state, with S‐heterocyclic derivatives being more reactive than the corresponding N‐containing compounds. In general, pentadienyl cations generated by protonation of alkoxytrienes were expected to react faster than those obtained by protonation of the corresponding dienones, as the latter were stabilized by a hydrogen bond. The presence of a substituent on the heterocyclic ring significantly affects the stereoselectivity (torquoselectivity) only in the case of the N‐heterocyclic derivatives, in which a 2‐alkyl group is axially oriented, providing the cis‐2,5‐disubstituted isomer only. Instead, with substituted S‐heterocyclic compounds, the anticipated torquoselectivity was very low and, in fact, a 3:1 diastereomeric mixture between the transand cisproducts was experimentally found after ring closure. For this study, the synthesis of the appropriate N‐ and S‐containing dienones and alkoxytrienes was realized to evaluate the predictivity power of the DFT computations, which was very good in all of the cases examined, both in terms of reactivity and stereoselectivity. The consistency observed between computational and experimental results, therefore, shows the usefulness of DFT calculations at the B3LYP/6‐311G** level of theory as a robust instrument for the prediction of reactivity and stereoselectivity in the Nazarov electrocyclic reaction.

The treatment of propargylic acetals with various lithium and mixed lithium–potassium Schlosser reagents, has allowed a one-pot synthesis of (E)-1,3-enynes, 1,3-diynes and allenes, depending on the reaction conditions and the selected base. Various reaction conditions were investigated in order to control the selectivity of the reactions and to obtain pure products. The metallation–elimination sequence in the presence of a suitable electrophile has provided a linear route to functionalized (E)-conjugated enynes, diynes and allenes.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Alkoxydienyl boronates 1a and 1b and alkoxystyryl boronate 2 have been used in various copper mediated cross-coupling reactions with azoles. A variety of N-alkoxydienyl- and N-styrylazoles have been synthesized under mild conditions. The process utilizes Cu(OAc)2 in the presence of CsF in CH2Cl2 at room temperature. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Alkoxy-functionalized butadienylboronic esters have been synthesized starting from α,β-unsaturated acetals and cross-coupled with both N-protected and N-unprotected 2-bromo- and 2-iodoaniline, and with 2-iodophenol. In particular, N-tosyl-protected dienylanilines can be transformed under mild conditions into quinolines and quinolinones, in the presence of a PdII catalyst. Moreover, the cross-coupling reaction between butadienylboronic esters and iodophenol directly affords chromenes that can be successively transformed into chromenones. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

The reaction of various α,β-unsaturated acetals with two equivalents of the Schlosser reagent LIC-KOR [equimolar mixture of BuLi (LIC), and tBuOK (KOR)] gives 1-metalated (1E)-1-alkoxy-1,3-dienes. These products can be transformed into trienic derivatives that are apt to participate in intramolecular Diels–Alder (IMDA) cycloaddition reactions, and can also be transformed into bifunctional (γ-halo-α-carbonyl) reagents. Moreover, the metalated dienes can be readily functionalized with suitable electrophiles to afford products that have been found to be useful reagents for the Stille and Suzuki cross-coupling reactions or arylated according to the conditions of the Heck process. Other significant syntheses of dienic and polyenic structures are reported along with some of their applications in organic synthesis. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Density functional theory (DFT) has been used to define the energy profiles of the Nazarov reaction involving cyclic systems. The calculations were carried out at the B3LYP/6‐311G** level of theory and the solvent (dichloromethane) contribution was estimated by using the recently developed SM5.43R solvation model. DFT calculations were first carried out to determine the energy profiles associated with the electrocyclization reactions of 3‐hydroxy‐ and 3‐ethoxypentadienyl cations in which one of the double bonds is embedded in O‐heterocyclic and carbocyclic systems. In particular, the effects on the reaction rate of modifications to the substrate, as well as the presence of the heteroatom in the cycle, have been investigated. The torquoselectivity of the electrocyclization reaction was then explored with substituted O‐heterocycles to understand the factors that control the stereochemical outcome of the process that preferentially provides 2,5‐trans‐disubstituted products. These DFT‐based results rationally explain most of the experimental observations related to the Nazarov reaction of the substrates herein investigated and could be useful in the rational interpretation, and likely in the prediction, of the outcome of Nazarov reactions involving other cyclic systems.

α,β-Unsaturated and α-phenyl acetals show different reactivity when treated with LIC-KOR superbase and trialkylboranes, in the presence of the reagent system PdL4-ArX (Suzuki−Miyaura cross-coupling conditions). In particular, unsaturated acetals yield gem-dialkylbutadienes via the formation of an intermediate π-allyl complex that facilitates an anionotropic alkyl migration; in the case of α-phenyl derivatives, the corresponding cross-coupling products are recovered. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

In this review some results are reported that allow the acetal group of α,β-unsaturated carbonyl derivatives to be considered not simply a protective function but also a synthetic tool for transforming aldehydes (and ketones) into a cheap and easily accessible starting material for the construction of various and more complex structures. The reported results can be grouped into three main sections: α,β-unsaturated as masked acyl anions, as precursor of dienophilic moieties, and as reagent in organometallic syntheses. In many reported examples the key reagents are polar organometallic reagents, and in particular, the bimetallic (lithium-potassium) mixed base LICKOR, which is also known as Schlosser's superbase. We are not acquainted with previous reviews on these topics, and in our survey we have considered the literature later than the eighties.

Molecularly imprinted polymers (MIPs) for 17β-estradiol were prepared following a multistep procedure including swelling and polymerization using polystyrene seeds, 4-vinylpyridine as the functional monomer and ethylene glycol dimethacrylate (EDMA) as crosslinker. Dibutylphthalate (DBF) and toluene were employed as swelling and porogenic compounds. All the samples showed a monomodal and very narrow diameter distribution with mean diameter values in the 2.0–4.7 μm range. The microspheres prepared in the presence of the template molecule present surface available vinyl pyridine unit content higher than those prepared without the template. The amphiphilic nature of the pre-polymerization complex between vinyl pyridine and 17β-estradiol can be claimed to be responsible for a preferential location of the vinyl pyridine units at the microsphere surface. The ability of molecular recognition depends on the accessibility of interaction sites located on surface of polymeric particles that increases when the ratios EDMA/polystyrene seed and DBF/polystyrene seed increase. TEM micrograph of sample PI4.

Treatment of the dimethyl acetals of citral (1) and farnesal (2) with the superbase “LICKOR” in THF at low temperatures induces regioselective metallation at the allylic methyl group at C(3). The metal–hydrogen exchange promotes immediate 1,4-elimination, yielding an (E)-configured conjugate alkyloxy-functionalized diene. The elimination product can be subjected to a Diels–Alder reaction, which allows further synthetic elaboration. In particular, in the case of farnesal dimethyl acetal the cycloaddition process leads to a derivative that can be transformed into a potential mimic agent of Juvenile hormones.

Irradiation of both aliphatic and aromatic thiocarbamate herbicides in an aqueous suspension of titanium dioxide leads to their efficient decomposition (maximum quantum yield up to 0.12 for the aliphatic derivatives, lower for the aromatic derivatives). The process involves the surface-adsorbed substrate, and is initiated through hydrogen abstraction by the hydroxyl radical from the N-alkyl chain (not from the S-alkyl chain unless this is a benzyl group) as indicated by the characterization of the main degradation intermediates.

Pseudoguaianolides belong to the class of sesquiterpene lactones and are characterized by the lactone ring cisor trans-anellated (in 6,7- or 7,8- position) to fused seven- and five-membered rings; they differ from guaianolides for the position of the methyl group in 5. The unusual tricyclic fused core 5/7/5 was a challenge and inspired new synthetic methodologies to install substituents with proper stereochemistry. Despite their potential of application in different fields, their exploitation is so far very limited. Because of this, with this review we wanted to give perspectives in terms of availability and resupply of the most active compounds of the class.

Iodobenzene and tetrakis(triphenylphosphine)palladium(0) [(C₆H₅)₃P]₄Pd catalyse a new synthesis of 1,1-dialkylbuta-1,3-dienes, starting from 1,1-diethoxybut-2-ene and trialkylboranes, in the presence of Schlosser’s superbase LIC–KOR.

Review: 51 refs.

Alkoxydienamides (III) are synthesized by the reaction of α,β‐unsaturated acetals (I) with isocyanates in the presence of Schlossers superbase LIC—KOR.

It provides a highly enantioselective approach to ethoxydienamines.

Review: 95 refs.

A phosphine‐free Pd‐catalyzed heteroannulation of o‐iodophenol (I) or o‐iodoaniline derivatives (V), (VIII) with alkoxyallenes (II), (IX) is presented.

Review: e.g. pyridines, pyrans, thiopyrans and pyrroles; 127 refs.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.