The biosynthesis of the thiazole phosphate moiety of thiamin (vitamin B1): the early steps catalyzed by thiazole synthase

Thiazole synthase (ThiG) catalyzes an Amadori-type rearrangement of 1-deoxy-d-xylulose-5-phosphate (DXP) via an imine intermediate. In support of this, we have demonstrated enzyme-catalyzed exchange of the C2 carbonyl of DXP. Borohydride reduction of the enzyme DXP imine followed by top-down mass spectrometric analysis localized the imine to lysine 96. On the basis of these observations, a new mechanism for the biosynthesis of the thiazole phosphate moiety of thiamin pyrophosphate in Bacillus subtilis is proposed. This mechanism involves the generation of a ketone at C3 of DXP by an Amadori-type rearrangement of the imine followed by nucleophillic addition of the sulfur carrier protein (ThiS-thiocarboxylate) to this carbonyl group.     

The mutual influence of the imine substituents of terephthal-bis-imines concerning their reactivity towards Fe2(CO)9

The reaction of terephthal-bis-imines with Fe₂(CO)₉ proceeds via a C---H activation reaction in the ortho position with respect to one of the imine functions. The corresponding hydrogen atom is shifted towards the former imine carbon atom producing a methylene group instead. The dinuclear iron complexes formed by this reaction sequence and showing no coordination of the second imine group were isolated from reactions of bis-imines with both phenyl and cyclohexyl substituents at the imine nitrogen atoms. In addition, we observed three different reaction pathways of the second imine substituent of the starting material which is obviously thus influenced by the fact that the first one is coordinating an Fe₂(CO)₆ moiety. If the organic substituent at the imine nitrogen atoms is a phenyl group the formation of a trinuclear complex is achieved in which an additional Fe(CO)₃ group is coordinating the CN double bond and one of the carbon---carbon bonds of the central phenyl ring in an η⁴-fashion. The same reaction leads to the isolation of a tetranuclear iron---carbonyl compound in which both imine substituents were transformed via the pathway described above, each building up dinuclear subunits. In contrast to this the reaction of a bis-imine with cyclohexyl groups at the imine nitrogen and thus an enhanced nucleophilicity leads to the formation of a tetranuclear complex in which only one imine group reacts under C---H activation with subsequent hydrogen migration towards the former imine carbon atom. The second imine substituent also shows a C---H activation reaction in the ortho position with respect to the imine group but the corresponding hydrogen atom is transferred to one of the aromatic carbon atom of the central phenyl ring of the ligand. The C=N double bond remains unreacted and only coordinates the second Fe₂(CO)₆ moiety via the nitrogen lone pair.     

Fragmentation of peptides with N-terminal dimethylation and imine/methylol adduction at the tryptophan side-chain

The reaction between formaldehyde and the side-chain of tryptophan results in a methylol adduct. This methylol adduct formation also occurs during reductive methylation reactions. In the current study, we investigate the fragmentation pattern of peptides with N-terminal dimethylation and methylol adduction at the tryptophan side-chain. Once formed, the methylol group can easily undergo water loss to form an imine. The peptides with imine or methylol adduct on tryptophan exhibit similar MS/MS fragmentation patterns. We observed ions resulting from an intramolecular reaction between the dimethylamino group at the peptide N-terminus or the lysine side-chain and the imine group. This reaction reduces the imine to a methyl group. We also observed the loss of the imine adduct on tryptophan. This reaction is likely to occur through the reaction of an amino or hydroxyl group with the imine adduct followed by subsequent loss of methylenimine or formaldehyde.     

Manipulating replication processes within a dynamic covalent framework

The reaction of an amine bearing an amidopyridine recognition site and an aldehyde bearing a carboxylic acid recognition site affords an imine that is capable of directing its own formation through a dynamic covalent replication cycle. Additionally, the amine, formed by reduction of the replicating imine, is a more efficient catalyst for the formation of the replicating imine than the imine is a catalyst for its own formation.     

Electronic and steric control in regioselective addition reactions of organolithium reagents with enaldimines

A reaction mode of imines derived from naphthalene-1-carbaldehyde and acyclic alpha,beta-unsaturated aldehydes with organolitium reagents was dependent on the characteristic nature of a substituent on the imine nitrogen atom. An imine having an electron-withdrawing aryl group on the nitrogen atom behaves as a 1,2-directing imine toward organolithium reagents. In contrast, an imine bearing an alkyl or a bulky aryl group favors 1,4-addition of organolithium reagents. Electronic and steric tuning of a substituent on the imine nitrogen atom for a reaction mode was rationalized on the basis of molecular orbital calculations.     

Stereoconversion of amino acids and peptides in uryl-pendant binol schiff bases

(S)-2-Hydroxy-2'-(3-phenyluryl-benzyl)-1,1'-binaphthyl-3-carboxaldehyde (1) forms Schiff bases with a wide range of nonderivatized amino acids, including unnatural ones. Multiple hydrogen bonds, including resonance-assisted ones, fix the whole orientation of the imine and provoke structural rigidity around the imine C==N bond. Due to the structural difference and the increase in acidity of the alpha proton of the amino acid, the imine formed with an L-amino acid (1-l-aa) is converted into the imine of the D-amino acid (1-D-aa), with a D/L ratio of more than 10 for most amino acids at equilibrium. N-terminal amino acids in dipeptides are also predominantly epimerized to the D form upon imine formation with 1. Density functional theory calculations show that 1-D-Ala is more stable than 1-L-Ala by 1.64 kcal mol(-1), a value that is in qualitative agreement with the experimental result. Deuterium exchange of the alpha proton of alanine in the imine form was studied by (1)H NMR spectroscopy and the results support a stepwise mechanism in the L-into-D conversion rather than a concerted one; that is, deprotonation and protonation take place in a sequential manner. The deprotonation rate of L-Ala is approximately 16 times faster than that of D-Ala. The protonation step, however, appears to favor L-amino acid production, which prevents a much higher predominance of the D form in the imine. Receptor 1 and the predominantly D-form amino acid can be recovered from the imine by simple extraction under acidic conditions. Hence, 1 is a useful auxiliary to produce D-amino acids of industrial interest by the conversion of naturally occurring L-amino acids or relatively easily obtainable racemic amino acids.     

Oligo(ethylene imine)-grafted glycidyl methacrylate linear and star homopolymers: Odd–even correlated transfection efficiency

The present study aims to investigate an odd–even effect of the number of ethylene imine units in the side-groups of totally abiotic synthetic polymers on their efficiency in DNA transfection. A library of fifteen polymers was fabricated. Two star homopolymers and one linear homopolymer based on glycidyl methacrylate were synthesized and used as precursors to which five linear oligo(ethylene imine)s (OEI) were grafted. The number of ethylene imine groups of the OEIs was varied. Specifically, ethylene diamine, diethylene triamine, triethylene tetramine, tetraethylene pentamine, and pentaethylene hexamine were used. Each of these fifteen OEI-grafted polymers was evaluated in terms of their efficiency to transfer plasmid DNA encoding firefly luciferase in C2C12 mouse myoblast cells. The transfection efficiency displayed an odd-even pattern, with all OEI-grafted polymers with an odd number of ethylene imine repeating units exhibiting higher transfection efficiency compared with those possessing an even number of ethylene imine repeating units. The odd–even effect was more pronounced for the star polymers with longer arms (degree of polymerization, DP = 100), while in case of the linear polymers, the odd–even effect was only observed for the lowest polymer loading. The cytotoxicity of the OEI-grafted polymers also followed an odd–even pattern, with the OEI-grafted star polymers with an arm DP of 100 and the linear polymers clearly presenting an odd-even effect, while the cytotoxicity of the OEI-grafted star polymers with an arm DP of 20 slightly increased with the number of ethylene imine repeating units.     

Unveiling the Local Structure of Palladium Loaded into Imine‐Linked Layered Covalent Organic Frameworks for Cross‐Coupling Catalysis

Layered covalent organic frameworks (2D‐COFs), composed of reversible imine linkages and accessible pores, offer versatility for chemical modifications towards the development of catalytic materials. Nitrogen‐enriched COFs are good candidates for binding Pd species. Understanding the local structure of reacting Pd sites bonded to the COF pores is key to rationalize interactions between active sites and porous surfaces. By combining advanced synchrotron characterization methods with periodic computational DFT modeling, the precise atomic structure of catalytic Pd sites attached to local defects is resolved within an archetypical imine‐linked 2D‐COF. This material was synthesized using an in situ method as a gel, under which imine hydrolysis and metalation reactions are coupled. Local defects formed in situ within imine‐linked 2D‐COF materials are highly reactive towards Pd metalation, resulting in active materials for Suzuki–Miyaura cross‐coupling reactions.     

Reversible polymerization driven by folding

Bisfunctionalized m-phenylene ethynylene imine oligomers were polymerized in the polar solvent acetonitrile, resulting in high-molecular weight poly(m-phenylene ethynylene imine)s. It is hypothesized that this polymerization, which proceeds through the reversible metathesis of imine bonds, is driven by the folding of the long m-phenylene ethynylene imine chains. Upon conducting the polymerization in a series of solvents in which the m-phenylene ethynylene oligomers exhibit different folding stabilities, it was possible to correlate the molecular weight of the resulting poly(m-phenylene ethynylene imine)s with the helical stability of the corresponding oligomers. The polymerization was also demonstrated to be reversible and responsive to solvent and temperature changes.     

Enantioselective synthesis of alpha-substituted ketones by asymmetric addition of chiral zinc enamides to 1-alkenes

A zinc enamide of a chiral imine derived from a ketone and (S)-valinol or (S)-t-leucinol undergoes addition to 1-alkene to generate a gamma-zincioimine intermediate, which reacts with a carbon electrophile to give upon hydrolysis an optically active alpha-substituted ketone in good yield. The stereoselectivity of the addition reaction may reach 99% for the reaction of a cyclohexanone imine with ethylene.     

Catalytic,three-component assembly reaction for the synthesis of pyrrolidines

[reaction: see text] Copper(I) salts catalyze the three-component assembly reaction between an alpha-diazo ester, an imine, and various alkenes and alkynes to form substituted pyrrolidines with excellent to good diastereoselectivities in high yields. The transition metal-catalyzed decomposition of the alpha-diazo compound in the presence of the imine likely generates a transient azomethine ylid that undergoes addition with various dipolarophiles in a highly convergent manner.     

Ruthenium-catalyzed reductive cyclization of nitroarenes with trialkylamines leading to quinolines

Nitroarenes react with trialkylamines in the presence of a catalytic amount of a ruthenium catalyst together with tin(II) chloride dihydrate at 180 °C in an aqueous medium (toluene–H₂O) to afford the corresponding quinolines in moderate to good yields. The catalytic pathway seems to be proceeded via a sequence involving initial reduction of nitroarenes to anilines, alkyl group transfer from alkylamines to anilines to form an imine, dimerization of imine, and heterocyclization.     

Cu(II) catalyzed imine C-H functionalization leading to synthesis of 2,5-substituted 1,3,4-oxadiazoles

A direct access to symmetrical and unsymmetrical 2,5-disubstituted [1,3,4]-oxadiazoles has been accomplished through an imine C-H functionalization of N-arylidenearoylhydrazide using a catalytic quantity of Cu(OTf)(2). This is the first example of amidic oxygen functioning as a nucleophile in a Cu-catalyzed oxidative coupling of an imine C-H bond. These reactions can be performed in air atmosphere and moisture making it exceptionally practical for application in organic synthesis.     

Photodifluoramination of a series of hexafluoroacetone imines

Gas phase irradiation of N₂F₄ (NF₂) in the presence of hexafluoroacetone imine (I), N-chlorohexafluoroacetone imine (II), or N-bromohexafluoroacetone imine (III) resulted in the formation of products that correspond to either perhalogenation of the unsaturation or conversion of the substrate to a saturated halocarbon. The mechanism suggested involves the formation of an imino radical that reacts with N₂F₄(NF₂) to produce N,N-difluorohydrazone, (CF₃)₂CNNF₂. A bimolecular homolytic displacement (S_H2′) by Cl and F on the hydrazone forms an intermediate diazene which leads to the observed products. N-fluorohexafluoroacetone imine is inert to F atoms and NF₂ under the reaction conditions.     

Novel N-phosphonio imine-catalyzed epoxidation reactions

A new type of acyclic N-phosphonio imine catalyst for selective epoxidations has been synthesized. The activity of these imine catalysts can easily be modulated by varying its substituents. The substituent attached to the imine nitrogen atom is particularly important for an efficient oxygen transfer.     

Role of cyclic dithiocarbonate as a promoter in the reaction of epoxide and imine in the presence of water

It was demonstrated that the reaction of epoxide and imine as a latent initiator under highly humid conditions was accelerated by addition of 5‐phenoxymethyl‐1,3‐oxathiolane‐2‐thione ( 1 ). When 1 was added to a mixture of glycidyl phenyl ether and an imine, the reaction of the epoxide with an amine released from the imine became faster than was the case without 1 , that is, 1 worked as a promoter of the reaction. The curing rate and initial adhesive strength of epoxy resin increased compared with that without 1 . © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4276–4283, 2004     

Dynamic Ligand Reactivity in a Rhodium Pincer Complex

Ligand cooperativity provides (transition) metal complexes with new reactivities in substrate activation and catalytic reactions, but usually the ligand acts as an internal (Brønsted) base, while the metal acts as a (Lewis) acid. We describe the synthesis and stepwise activation of a new phosphane‐pyridine‐amide ligand PNN^H2 in combination with Rh^I. The ligand is susceptible to stepwise proton and hydride loss from the nitrogen arm (imine formation) and deprotonation at the pyridylphosphine arm (dearomatization), giving rise to amine complex 1 , amido species 2 , imine complex 3 and dearomatized compound 4 . Complex 4 bears a dual‐mode cooperative PNN′ ligand containing both a (nucleophilic) basic methine fragment and a reactive (electrophilic) imine moiety. The basic ligand arm enables substrate deprotonation while the imine ligand arm enables reversible “storage” of the activated (nucleophilic) form of a sulfonamide substrate at the ligand. In combination with metal‐based reactivity, this allows for the mono‐alkylation of o‐toluenesulfonamide with iodomethane. Compounds 1 , 3 and 4 are structurally characterized. We also report the first structurally characterized example of an aminal in the coordination sphere of rhodium, complex 5 , [Rh(CO)( PNN′′ )], formed by sequential N?H activation of sulfonamide by the dearomatized ligand PNN′ and follow‐up nucleophilic attack of anionic sulfonamide onto the imine fragment.     

Mécanismes de Formation d'α-Aminophosphonates

When di-n-decylphosphonate 1a or di-benzylphosphite 1b are reacted with furan imine 2a or thiophenic imine 2b , the reaction leads to an f -aminophosphonate: 3a , 3b , or 3c following an ion- or radical-based reaction.     

Origin of the relative stereoselectivity of the beta-lactam formation in the Staudinger reaction

The relative (cis, trans) stereoselectivity of the beta-lactam formation is one of the critical issues in the Staudinger reaction. Although many attempts have been made to explain and to predict the stereochemical outcomes, the origin of the stereoselectivity remains obscure. We are proposing a model that explains the relative stereoselectivity based on a kinetic analysis of the cis/trans ratios of reaction products. The results were derived from detailed Hammett analyses. Cyclic imines were employed to investigate the electronic effect of the ketene substituents, and it was found that the stereoselectivity could not be simply attributed to the torquoelectronic model. Based on our results, the origin of the relative stereoselectivity can be described as follows: (1) the stereoselectivity is generated as a result of the competition between the direct ring closure and the isomerization of the imine moiety in the zwitterionic intermediate; (2) the ring closure step is most likely an intramolecular nucleophilic addition of the enolate to the imine moiety, which is obviously affected by the electronic effect of the ketene and imine substituents; (3) electron-donating ketene substituents and electron-withdrawing imine substituents accelerate the direct ring closure, leading to a preference for cis-beta-lactam formation, while electron-withdrawing ketene substituents and electron-donating imine substituents slow the direct ring closure, leading to a preference for trans-beta-lactam formation; and (4) the electronic effect of the substituents on the isomerization is a minor factor in influencing the stereoselectivity.     

The role of imine-enamine tautomerism in effecting cross-aldol condensations

An indirect method to effect cross-aldol coupling of two nonequivalent enolizable aldehydes is reported that involves initial conversion of one aldehyde to an imine derivative possessing an N-3° alkyl substituent. In sharp contrast to the related couplings (e.g., the use of α-lithiated imines at low temperature), condensation between the imine and several representative aldehydes occurs readily at ambient temperature in the presence of a catalytic amount of cobalt(II) chloride.