Synthesis and analysis of stable isotope-labelled N-acyl homoserine lactones

Aliphatic aldehydes were deuterated at the alpha-position via a base-catalyzed exchange reaction with D2O. These deuterated building blocks were used for the synthesis of labelled analogues of quorum sensing signal molecules belonging to the three major classes of naturally occurring N-acylated homoserine lactones (AHLs), with the label on a non-enolizable and therefore stable position. Besides the application of these stable isotope-labelled AHLs as a labelled standard for analysis via isotope dilution mass spectrometry, these compounds can be used to study the metabolic fate of the fatty acid tail of the AHL-molecule. These isotope-labelled compounds were fully characterized and used to synthesize the deuterated analogues of two commonly occurring AHL-degradation products, a tetramic acid and a ring opened N-acyl homoserine

Synthesis and biological evaluation of novel N-α-haloacylated homoserine lactones as quorum sensing modulators

Novel N-α-haloacylated homoserine lactones, in which a halogen atom was introduced at the α-position of the carbonyl function of the N-acyl chain, have been studied as quorum sensing (QS) modulators and compared with a library of natural N-acylated homoserine lactones (AHLs). The series of novel analogues consists of α-chloro, α-bromo and α-iodo AHL analogues. Furthermore, the biological QS activity of the synthetic AHL analogues compared to the natural AHLs was evaluated. Halogenated analogues demonstrated a reduced activity in the Escherichia coli JB523 bioassay, with the α-iodo lactones being the less active ones and the α-chloro AHLs the most potent QS agonists. Most of the α-haloacylated analogues did not exhibit a significant reduction when tested in the QS inhibition test. Therefore, these novel analogues could be utilized as chemical probes for QS structure–activity studies

Synthesis of novel β-aminocyclobutanecarboxylic acid derivatives by a solvent-free aza-Michael addition and subsequent ring closure

Novel beta-aminocyclobutanecarboxylic acid derivatives were prepared via a sequential solvent-free aza-Michael addition of benzophenone imine across 3-halopropylidenemalonates and base-induced ring closure. These highly substituted cyclobutanedicarboxylic acid derivatives were subjected to a reactivity study which demonstrated the tendency of these donor-acceptor substituted four-membered rings to be converted into their corresponding ring-opened products

Synthesis and reactions of 1-amino-1,5,6,10b-tetrahydroimidazo[2,1-a]isoquinolin-2(3H)-ones

1-Amino-1,5,6,10b-tetrahydroimidazo[2,1-a]isoquinolin-2(3H)-ones, as previously unknown ring-annelated isoquinolines with a 3-aminoimidazolidin-4-one scaffold, were selectively prepared upon reacting 2-carbamoylmethyl- or 2-ethoxycarbonylmethyl-3,4-dihydroisoquinolinium salts with hydrazine hydrate. Acylation of the primary amino group with benzoyl chlorides, followed by reductive ring cleavage of the annelated 4-imidazolidinone ring and final cyclodehydration of the N,N'-diacylhydrazines resulted in the synthesis of 1-methyl-2(5-aryl-[1,3,4]oxadiazol-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolines which are of interest due to their potential use as bioisosteres of biologically active N-aryl-2-(1-methyl-3,4-dihydro-1H-isoquinolin-2-yl) acetamides

A phytochemical perspective on plant defense against nematodes

Given the large yield losses attributed to plant-parasitic nematodes and the limited availability of sustainable control strategies, new plant-parasitic nematode control strategies are urgently needed. To defend themselves against nematode attack, plants possess sophisticated multi-layered immune systems. One element of plant immunity against nematodes is the production of small molecules with anti-nematode activity, either constitutively or after nematode infection. This review provides an overview of such metabolites that have been identified to date and groups them by chemical class (e.g., terpenoids, flavonoids, glucosinolates, etc.). Furthermore, this review discusses strategies that have been used to identify such metabolites and highlights the ways in which studying anti-nematode metabolites might be of use to agriculture and crop protection. Particular attention is given to emerging, high-throughput approaches for the identification of anti-nematode metabolites, in particular the use of untargeted metabolomics techniques based on nuclear magnetic resonance (NMR) and mass spectrometry (MS)

The Cu(OTf)2 catalysed microwave assisted synthesis of a new scaffold, 7-aryl-7,8-dihydropyrido[4,3-c]pyridazin-5(6H)-one

The synthesis of novel 7-aryl-7,8-dihydropyrido[4,3-c]pyridazin-5(6H)-ones is described including a one-step Mannich-type reaction followed by intramolecular ring closure of ethyl 3-methylpyridazine-4- carboxylate and aldimines, catalysed by the Lewis acid Cu(OTf)2 under microwave heating. This synthesis opens up possibilities to access this unexplored scaffold for medicinal chemistry

New general synthesis of alpha-alkoxyketones via alpha'-alkylation, alpha-alkylation and alpha,alpha'-dialkylation of alpha-alkoxyketimines

alpha-Methoxy- and alpha-ethoxyketones, as important intermediates in organic synthesis and flavor compounds in food chemistry, were synthesized by deprotonation of N-(1-alkoxy-2-propylidene)isopropylamine, prepared by condensation of the corresponding alpha-alkoxyacetone with isopropylamine, and subsequent reaction of the corresponding 1-azaallylic anions with alkyl halides to afford alpha'-alkylated, alpha-alkylated and alpha,alpha'-dialkylated ketimines. Hydrolysis of the imino function led to the desired substituted alpha-alkoxyketones. The ratio of alpha-, alpha'-, and alpha,alpha'-(di)alkylated compounds depended on the amount of base used and on the nature of the alkylating reagent

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

The asymmetric synthesis of new chiral gamma-chloro-alpha,beta-diaminocarboxylamide derivatives by highly diastereoselective Mannich-type reactions of N-(diphenylmethylene) glycinamides across chiral alpha-chloro-N-p-toluenesulfinylaldimines was developed. The resulting (S-S,2S,3S)-gamma-chloro-alpha,beta-diaminocarboxylamides were formed with the opposite enantiotopic face selectivity as compared to the (S-S,2R,3R)-gamma-chloro-alpha,beta-diaminocarboxyl esters obtained via Mannich-type addition of analogous N-(diphenylmethylene) glycine esters across a chiral alpha-chloro-N-p-toluenesulfinylaldimine. Selective deprotection under different acidic reaction conditions and ring closure of the gamma-chloro-alpha,beta-diaminocarboxylamides was optimized, which resulted in N-alpha-deprotected syn-gamma-chloro-alpha,beta-diaminocarboxylamides, N-sulfinyl-beta,gamma-aziridino-alpha-aminocarboxylamide derivatives, a trans-imidazolidine, and an N-alpha,N-beta-deprotected syn-gamma-chloro-alpha,beta-diaminocarboxylamide

Synthesis of new functionalized aziridine-2-and azetidine-3-carboxylic acid derivatives of potential interest for biological and foldameric applications

short synthesis of alkyl 2-(bromomethyl)aziridine-2-carboxylates and alkyl 3-bromoazetidine-3-carboxylates was developed involving amination, bromination, and base-induced cyclization of alkyl 2-(bromomethyl)acrylates. The aziridines are the kinetically favored cyclization products and could be transformed into 3-bromoazetidine-3-carboxylic acid derivatives via thermal isomerization. The new small-membered azaheterocyclic alpha- and beta-amino acid derivatives contain a bromo-substituted carbon center as a useful moiety for functionalization. Transformation of these functionalized azaheterocycles via nucleophilic substitution with carbon, sulfur, oxygen, and nitrogen nucleophiles and via elaboration of the amino and carboxyl group provided a broad range of new conformationally constrained aziridine-2- and azetidine-3-carboxylic acid derivatives, which are of interest from a biological point-of-view as well as for applications in the field of foldamers