De Mesmaeker Alain

Syngenta · Crop Protection Research

Strigolactones (SLs) are signaling molecules involved in plant development and governing interactions with soil microorganisms in the rhizosphere as well as the germination of parasitic weeds. Developing their use in Crop Protection is a promising approach to a sustainable agriculture by mitigating biotic and abiotic stresses. Recently, a new class...

Maize (Zea mays) is a major staple crop in Africa, where its yield and the livelihood of millions are compromised by the parasitic witchweed Striga. Germination of Striga is induced by strigolactones exuded from maize roots into the rhizosphere. In a maize germplasm collection, we identified two strigolactones, zealactol and zealactonoic acid, whic...

We describe herein a high yielding and metal‐free methodology to access 9‐aminophenanthrene derivatives and heterocyclic analogues starting from biaryl acetamides. The conversion of the substrates to their corresponding keteniminium salts triggers a spontaneous electrocyclization occurring at room temperature within a few minutes. DFT Calculations...

Keteniminium salts (KIs) are versatile intermediates in synthetic organic chemistry. Elucidation of the mechanistic aspects of KI formation reactions facilitates the design of KI intermediates that give access to complex compounds. In this study, in order to provide a comprehensive understanding of KI formation, various mechanisms were investigated...

Herein we described a novel 3-step synthesis of pyrrolizidinone derivatives with good overall yield. This sequence relies on first a [2+2] cycloaddition between a keteniminium salt intermediate, bearing an alkyl chloride side chain, and an alkene partner furnishing the corresponding cyclobutanone after hydrolysis of the resulting cyclobutaniminium....

Purpose Arbuscular mycorrhizal fungi (AMF) play important roles in agriculture because of their ability to improve plant resilience against abiotic and biotic stresses. AMF as a technology to promote a more sustainable agriculture holds great potential, yet many factors affect the efficiency of this plant-microbe symbiosis leading to inconsistency...

p class="Helv‐Abstract" style="margin:0cm;margin‐bottom:.0001pt"> Herein, we describe an effective one‐pot sequence for the regio‐ and stereoselective synthesis of highly substituted cyclobutanones. This process relies on first a [2+2] cycloaddition involving a keteniminium salt intermediate with an alkene followed by isomerization of the resulting...

Strigolactones are a family of plant secondary metabolites whose first member strigol was isolated in 1966 from the root exudates of cotton and identified as the germination inducer for the parasitic weeds of Striga and Orobanche species. Since 2008 the role of strigolactones as a new class of phytohormones has emerged and their role in controlling...

Strigolactones are plant hormones, which play pivotal roles in plant growth and development with potential application in sustainable agriculture. Recently, zealactone 1a/b has been identified as the major strigolactone from the root exudates of corn. Although zealactone is a promising molecule affecting signaling in the rhizosphere as well as in p...

Strigolactones (SLs) represent a class of plant hormones that regulate developmental processes and play a role in the response of plants to various biotic and abiotic stresses. Both in planta hormonal roles and ex planta signalling effects of SLs are potentially interesting agricultural targets. In this review, we explore various aspects of SL func...

A predictive computational study was conducted in order to assess the efficiency of electrocyclization reactions of keteniminium salts, in an effort to form a variety of heterocyclic systems, namely, 3-amino(benzo)thiophenes, 3-amino(benzo)furans, 3-aminopyrroles as well as 3-aminoindoles. A density functional theory (DFT) approach was utilized and...

Strigolactones are phytohormones, which affect diverse aspects of plant growth and development with potential application in modern agriculture. Recently, heliolactone has been isolated as a non‐canonical type of strigolactone from the root exudates of sunflower, and it could be involved in signaling in the rhizosphere as well as in planta. However...

Herein, we describe a high yielding approach towards the synthesis of 3‐amino‐indoles and –benzofurans via 6p‐electrocylization. This was made possible by taking advantage of the high reactivity of keteniminium salts, formed in‐situ by treating with triflic anhydride and 2‐fluoropyridine amides bearing at the alpha position either an aniline or a p...

Strigolactones have been known as signaling molecules in the rhizosphere of plants since more than 50 years. However, their roles as phytohormone have been only recognized since 2008. We describe here a very efficient synthetic access to representative canonical strigolactones displaying the A-B-C-D tetracyclic structure and to non-canonical strigo...

Herein, we describe a very straightforward and metal free method for the synthesis of benzazepinones via an intramolecular cyclization. This involves an ortho‐vinyl‐anilino‐amide as starting material which is converted to a keteniminium intermediate that spontaneously cyclize to form a 7‐membered ring iminium. Under slightly basic hydrolysis condit...

Ein ergiebiges Feld: Die vor einigen Jahren entdeckte Pflanzenhormonklasse der Strigolactone zeigt beispiellose biologische Aktivität. Deren Nutzung ist jedoch nicht ohne Hürden: Die Strigolactonsynthese und das Design der gewünschten Aktivität sind anspruchsvoll. Dieser Kurzaufsatz beschreibt den aktuellen Stand des Wissens über die Strigolactone...

Almost 80 years after the discovery of the first plant hormone, auxin, a few years ago a new plant hormone, the strigolactones, was discovered. These molecules have unprecedented biological activity in a number of highly important biological processes in plants but also outside the plant in the rhizosphere, the layer of soil surrounding the roots o...

Herein, we describe a facile approach towards the synthesis of diversely substituted 3‐aminothiophenes. A wide range of functional groups can be incorporated at the C‐2, C‐4 and C‐5 positions of the thiophenes and this route is also suitable for the synthesis of fused bicyclic heterocycles such as 3‐aminotetrahydrobenzothiophenes. This methodology...

Karrikin (KAR1) also named “karrikinolide” was isolated in 2004 from smoke water and identified as a very potent germination stimulant as well as controlling early seedling development for a large variety of plant species. We reported herein an unprecedented and scalable synthesis of Karrikin KAR1 based on an elegant and efficient 6‐endo‐dig cyclis...

We described a general approach to 3-aminobenzothiophenes and 3-aminothiophenes fused to 5-membered heteroaromatic rings as thiophenes, furans and pyrroles through a 6π-elctrocyclization reaction of keteniminium salts. We investigated various substituents not only on the aromatic rings, but also at C-2 and on the nitrogen atom of the keteniminium s...

γ-Lactams are important building blocks for the synthesis of biologically active molecules and can easily be accessed via Beckmann rearrangement of cyclobutanones. However, Beckmann fragmentation is often a competing reaction for these strained ketones. We found that performing the Beckmann rearrangement with Tamura’s reagent in the presence of aqu...

Strigolactones are plant hormones regulating essential stages of a plants development. Their low natural abundance combined with a low chemical stability significantly hampered the detailed investigation of their biological activity. Non-canonical strigolactones lack the fused tricyclic ABC-ring system commonly present in canonical-type strigolacto...

A flow chemistry process for the synthesis of 2-substituted cyclobutanones, via [2 + 2] cycloaddition of keteneiminium salts and ethylene gas, is reported. Our approach uses rapid and mild reaction conditions to access a diverse array of products with good to excellent yield, alongside a good level of functional group compatibility.

We have developed a very straightforward method for the synthesis of 4-membered ring alkaloid analogues via intramolecular [2+2] cycloadditions. This involves the cyclization of a keteniminium salt in which an alkene is linked by the nitrogen atom, and where, the resulting cyclobutane iminium is reduced in a diastereoselective manner. Competition r...

A flow chemistry process for the synthesis of 2-substituted cyclobutanones, via [2+2] cycloaddition of keteneiminium salts and ethylene gas, is reported. Our approach uses rapid and mild reaction conditions to access a diverse array of products with good to excellent yield, alongside a good level of functional group compatibility.

A systematic investigation of structural modifications of brassinosteroids is presented. We describe in detail their synthetic preparation, which includes significant improvements of previously reported protocols as well as access to new analogs with functional modifications of the steroid skeleton and of the C(17)-attached side chain. We report th...

In the root exudate and root extracts of maize hybrid cv NK Falkone seven putative strigolactones were detected using UPLC-TQ-MS-MS. All seven compounds displayed MS-MS-fragmentation common for strigolactones and particularly the presence of a fragment of m/z 97 Da, which may indicate the presence of the so-called D-ring, suggests they are strigola...

N,N-disubstituted amides of cyclobutanoic or phenylacetic acids and alkenes

Ketene iminium salts, generated by treatment of amides with Tf2O undergo a [2 + 2] cycloaddition with alkenes to form unstable cyclobuteneiminium salts which are reduced to give aminocyclobutanes (III) and (VIII).

We describe the first [2+2] cycloaddition between a keteniminium salt and an alkene followed by a nucleophilic addition on the in-situ generated cyclobuteniminium salts. This one-pot sequence enable the formation of quaternary centers with high level of stereoselectivity and is largely applicable to the synthesis of highly strained intermediates as...

We describe an efficient method for the synthesis of aminocyclobutanes via a [2+2] cycloaddition between a keteniminium salt and an alkene, followed by a reduction step. The use of easily removable N-allyl moieties as protecting groups increases the potential of this method to access, in a few steps, highly functionalized cyclobutaneamines-containi...

Background: Strigolactones play an important role in the rhizosphere as signaling molecules stimulating the seed germination of parasitic weed seeds and hyphal branching of arbuscular micorrhiza and also act as hormones in plant roots and shoots. Strigolactone derivatives e.g. strigolactams could be used as suicidal germination inducers in the abs...

New technologies able to mitigate the main abiotic stresses (i.e., drought, salinity, cold and heat) represent a substantial opportunity to contribute to a sustainable increase of agricultural production. In this context, the recently discovered phytohormone strigolactone is an important area of study which can underpin the quest for new anti-stres...

We describe a very efficient access to 3-aminobenzothiophenes using substituted phenylthioacetamides via a 6π-electrocylization of the corresponding keteniminium intermediates. The ease of this electrocyclization allows the use of N-allyl and N-diallyl protecting groups leading to the corresponding primary or secondary amines after mild deprotectio...

Very recently, strigolactones have been conclusively identified as phytohormones. The progresses achieved in this field are culminating in the identification of the molecular receptors involved in the signal transduction mechanism. The exact mechanism of the mode of action of strigolactones still remains to be fully elucidated and we were intereste...

A new efficient access to β-substituted cyclobutanones via Michael addition using cyclobuteniminium salts is described. Competition reactions have been performed in order to demonstrate the higher reactivity of cyclobuteniminium salts compared to their cyclobutenone analogues and the results have been rationalized by DFT calculation. Michael adduct...

The present invention provides a compound of formula (I) wherein R4 is of sub-formula (a) or (b) and wherein the other substituents are as defined in the specification. The compounds of formula (I) are potentially useful as herbicides.

The present invention relates to novel strigolactam derivatives of formula (I) to processes and intermediates for preparing them, to plant growth regulator compositions comprising them and to methods of using them for controlling the growth of plants and/or promoting the germination of seeds.

The synthesis of broad scope of novel monosubstituted cyclobuteniminium salts derived from aldo-keteniminium salts and acetylene or 1-propyne is described. The reactivity of cyclobuteniminium salts in Diels–Alder reactions has been studied in detail by DFT calculations and by performing competition reaction with cyclobutenone derivatives.

Two approaches to the strigolactone tricyclic lactone skeleton 2 were investigated using ketene/ketene-iminium cycloaddition to olefins. Finally, the first enantioselective access to the four stereoisomers of 5-deoxystrigol 1 is reported using an intramolecular [2+2] cycloaddition of homochiral ketene-iminium salts 5. Very high asymmetric control w...

An efficient access to cyclobutanone derivatives has been developed via a 'one-pot' [2+2]/[4+2] sequence involving keteniminium and cyclobuteniminium salts as key intermediates. A broad range of novel cyclobuteniminium salts have been prepared via [2+2] cycloaddition of keteniminium salts and alkynes. The resulting [2+2] adducts were then further t...

NOVELTY - Non-steroidal brassinosteroid mimetic derivatives (I) are new. USE - (I) are useful: in a plant growth regulator or seed germination promoting composition; for regulating the growth of plants at a locus; for promoting the germination of seeds; and for controlling weeds (all claimed). The ability of (I) to improve the growth of the plants...

Seed germination and early seedling development are essential events in the plant life cycle that are controlled largely by the interplay and cross-talk between several plant hormones. Recently, major progress has been achieved in the elucidation at the molecular level of the signalling of these phytohormones. In this review, we summarise the data...

A series of triketones 2 and 3 featuring novel fused bicyclic aryl ethers have been prepared. The syntheses utilized ring-closing olefin metathesis (compounds 2), or oxidative cyclization of allylphenols as the key steps. The herbicidal activity of the targeted triketones 2 and 3 on various grasses and broad-leaved weeds was determined and compared...

NOVELTY - Substituted 2-aminopyridine derivative (I), its salt and/or N-oxide is new. USE - As a plant growth regulator or a seed germination promoter; for regulating the growth of plants at a locus; for promoting the germination of seeds; and for controlling weeds (claimed). ADVANTAGE - The compound result in improved plant growth properties, su...

NOVELTY - Substituted amino azole derivatives (I) are new. USE - (I) including the excluded compounds are useful for regulating the growth of plants at a locus, germination of seeds and controlling weeds (all claimed), where the plants are e.g. wheat, barley, rye, oats, sugar beet, apples, pears, plums, peaches, cherries, strawberries, raspberries...

An intramolecular 6 phi/10 pi-electrocyclization from ketene-iminium salts was developed for the preparation of naphthylamines. Various substituents on the nitrogen, on the aromatic ring, and on the olefin were studied. Tricyclic skeletons were obtained in few steps and good overall yields. The electrocyclization of ketene-iminium salts has been co...

Strigolactones have been the latest identified phytohormones. Among the strigolactones analogues described recently, GR-24 remains the most studied derivative which is used as standard in this field. In order to improve several properties of GR-24 for potential agronomical applications, we investigated the effect of substituents on the B and C-ring...

NOVELTY - Substituted pyrrolidine containing heterocyclic compounds (I) are new. USE - (I) are useful as plant growth regulators or seed germination promoters and for controlling weeds (claimed) in e.g. cereals (wheat, barley, rye and oats), beet (sugar beet or fodder beet), fruits (pomes, apples, pears, plums, peaches, almonds, cherries, strawber...

NOVELTY - A non-steroidal brassinosteroid mimetic pyridine derivative (I), or its salt or N-oxide, is new. USE - As a plant growth regulator or seed germination promoting composition; for regulating the growth of plants at a locus; for controlling weeds; and for promoting the germination of seeds (claimed). The plant includes crops such as cereals...

NOVELTY - Substituted 2-amino-pyridine compounds (I) are new. USE - (I) are useful for regulating the growth of plants at a locus, promoting the germination of seeds, and controlling weeds (all claimed). The ability of (I) to regulate plant growth was tested on French beans (Phaseolus vulgaris) by measuring the length of the petiole of the second...

NOVELTY - Non-steroidal brassinosteroid mimetic derivatives (I) are new. USE - (I) are useful for: regulating the growth of plants at a locus; promoting the germination of seeds; and controlling weeds (all claimed). ADVANTAGE - (I) provides improved plant growth properties, such as faster growth, faster germination, earlier germination, and/or re...

Herein we report a very efficient access to a variety of bicyclic 1,3-diones as key intermediates to be incorporated into very potent HPPD inhibitors. In particular, we have developed a one-pot process for the synthesis of the bicyclo[3.2.1]octane-2,4-dione, the parent dione of Bicyclopyrone.

An intramolecular [2+2] cycloaddition of ketenes and ketene-iminium was developed for the preparation of GR-24, a synthetic analogue of the family of strigolactone plant hormones. Excellent levels of regioselectivity and of chiral induction were obtained using a bulky chiral amine for the formation of the cyclobutanone and a subsequent regioselecti...

We report here the use of the readily accessible ethyl-2-(2-chloroethyl)acrylate as a new very versatile α-cyclopropylester cation synthon, which reacts efficiently and selectively with carbon-, nitrogen-, sulfur- or phosphorus-centered nucleophiles through Michael addition followed by intramolecular capture of the incipient ester enolate to afford...

Eleven different types of backbone replacements have been investigated. The thermodynamic stability of the duplexes formed between these modified oligonucleotides and their RNA complements are summarized. Among these backbone replacements, we identified two amide derivatives which display improved properties for their application to the antisense s...

We report the design and the efficient synthesis of novel spirocyclopropyl cyclohexane-1,3-dione and -1,3,5-trione units to be incorporated into potent HPPD inhibitors. New routes involving original combinations of synthetic equivalents of α-cyclopropyl ketone-α-anion and α-cyclopropyl ester-β-cation are described.

Isocyanide-based multicomponent reactions of the Ugi- and Passerini-type have been valuable tools for the rapid exploration of the novel fungicidal compound classes of phenylglycinamides and mandelamides. Mandipropamid (6), which was discovered during this derivatisation, displays excellent activity against the economically important phytopathogens...

Thermodynamic and structural properties of a chemically modified DNA-RNA hybrid in which a phosphodiester linkage is replaced by a neutral amide-3 linkage (3'-CH(2)-CONH-5') were investigated using UV melting experiments, molecular dynamics simulations in explicit water, and continuum solvent models. van't Hoff analysis of the experimental UV melti...

Novel types of oomycete fungicides have been designed and prepared. The synthetic approach to these N-sulfonyl amino acid amides is outlined. Bioassays demonstrate their high efficacy against important plant diseases like Phytophthora infestans (tomato and potato late blight) and Plasmopara viticola (grape downy mildew). Structure–activity relation...

A short, efficient synthesis of 5′-amino-5′-(S)-methyl-2′,5′-dideoxynucleosides 1 has been developed through the diastereoselective addition of methylmagnesium bromide or methyllithium to an intermediate tert-butylsulfinimide.

A short, efficient synthesis of 5'-amino-5'-(S)-methyl-2',5'-dideoxynucleosides 1 has been developed through the diastereoselective addition of methylmagnesium bromide or methyllithium to an intermediate tert-butylsulfinimide.

In this paper we summarize our efforts toward optimizing key reactions on the solid phase which tolerate a variety of functional groups. These groups were sequentially modified, allowing the production of novel and diverse compound libraries on the solid phase.

In this paper we summarize our efforts toward optimizing key reactions on the solid phase which tolerate a variety of functional groups. These groups were sequentially modified, allowing the production of novel and diverse compound libraries on the solid phase.

Radical cyclization reactions involving precursors derived from cyclohexadiene diols were investigated, both, in solution and on the solid phase. A straightforward sequence was established in solution to obtain bicyclic compounds with potential for diversity. Optimized reaction procedures were applied to solid phase synthesis.

2′-Deoxyribo polyamide nucleic acids (2′-deoxyribo-PNAs) 3 are a new class of DNA analogs with a 2′,3′-dideoxyribose-polyamide backbone structure. 2′-Deoxyribo-PNAs as well as chimeric oligonucleotide analogs with a mixed DNA / 2′-deoxyribo-PNA structure bind to single stranded complementary nucleic acids with similar affinities as natural DNA.

Levoglucosan was decorated with a variety of substituents at various sites while being bound to a solid support.

Radical cyclization of aryl iodides bound to polystyrene is described together with the trapping of the resulting radical, prior to its reduction, by allyltributyl tin.

A highly efficient sequence for the synthesis of complex, chiral and highly functionalized molecules on solid phase is reported. Solid phase bound cyclohexadiene-diols were derivatized through epoxidation, nucleophilic ring opening, Pd(O) cross-couplings and Diels-Alder reactions.

The scope and limitations of Pd(0)-mediated coupling reactions between aromatic halides linked to a polystyrene resin and boronic acid derivatives (Suzuki coupling), aromatic and vinylic tin compounds (Stille coupling), as well as thiols are reported. For all reactions, conditions were optimized and evaluated with various reagents. In many cases, u...

In this paper we report the scope and limitations of Pd(0)-mediated coupling reactions between aromatic iodides linked to a polystyrene resin and terminal acetylenes and olefins (Heck reactions). Optimized reaction conditions were evaluated with a number of different reagents. The optimized reaction conditions were frequently found to be superior t...

The amide backbone modification C3′-CH2-CONH-C5′ has been further modified by introducing a methyl at C5′, either in R or in S configuration. Only the S stereoisomer can adopt the required geometry to fit into a duplex with complementary RNA. Additional O-methyl groups at C2′ of the furanose generate antisense oligonucleotides with considerably imp...

The synthesis of the amide dimers 3-5 carrying a potential intercalating substituent on the nitrogen atom of the backbone is presented, together with the incorporation of these modifications into oligonucleotides, the resulting melting temperatures (T-m's) of the corresponding duplexes with RNA- and DNA- complements and a summary of molecular model...

Eighteen different types of backbone replacements have been investigated. The thermodynamic stability of the duplexes formed between these modified oligonucleotides and their RNA complements are summarized. Among these backbone replacements, we identified two amide derivatives which display improved properties fort their application to the antisens...

Five dimers containing amide linkages instead of the natural phosphodiester linkage were synthesized and incorporated into oligonucleotides. The length of the amide backbone was varied. The hybridization properties of the modified oligonucleotides with RNA complements and their conformational analysis are described and compared to previously report...

An increased stability of duplexes between amide-modified oligonucleotides (depicted on the right) and RNA was achieved by the introduction of 2′-OMe groups. Since the modified oligonucleotides display a very high affinity for their RNA complement and are more stable towards nucleases, they can be considered as promising antisense agents. X = H, OH...

The incorporation of hydrophobic substituents on the amide functionality of modified oligonucleotides drastically influences the thermal stability of the corresponding duplexes with the RNA complement.

Four acetylene-containing dimers were synthesized and incorporated into oligonucleotides. The hybridization properties of the modified oligonucleotides to RNA complements and their conformational analysis are reported. Copyright (C) 1996 Elsevier Science Ltd

The two olefinic backbone replacements III and IV were synthesized and incorporated into oligonucleotides. The hybridization properties of the modified oligonucleotides to DNA and RNA complements and conformational analyses of III and TV are compared to the corresponding amide modifications I and II.

In the past year major advances have been made in the design, synthesis and characterization of two classes of modified oligonucleotides. In the first class, the phosphodiester backbone of 2'-deoxyribo-oligonucleotides has been replaced in several different ways. The second group represents a completely different type of oligonucleotide modificatio...

The effect of the replacement of the natural phosphodiester linkage -C3'-O-PO2-O-CH2-C4'- in the DNA strand of RNA.DNA hybrid duplexes by either of the two amide linkages -C3'-CH2-CO-NH-CH2-C4'- or -C3'-CH2-NH-CO-CH2-C4' has been investigated by molecular mechanics (MM) and molecular dynamics (MD) simulations. Conformational analysis has been used...

Oligodeoxyribonucleotides incorporating 2′- or 6′-alkoxy substituted carbocyclic nucleotide units are shown to bind to complementary RNA with lower affinity than their unmodified parent compounds, while the presence of stretches of contiguous 6′-hydroxy substituted building blocks enhances RNA-binding affinity. 6′-substituted carbocyclic nucleotide...

A variant form of a group I ribozyme, optimized by in vitro evolution for its ability to catalyze magnesium-dependent phosphoester transfer reactions involving DNA substrates, also catalyzes the cleavage of an unactivated alkyl amide when that linkage is presented in the context of an oligodeoxynucleotide analog. Substrates containing an amide bond...

The synthesis of a thymidine dimer containing a thiocarbamate moiety as internucleosidic linkage replacement is described. This new dimer was incorporated in oligodeoxyribonucleotides and the melting temperatures (Tm’s) of the DNA/RNA duplexes were determined.