Asymmetric total synthesis of (-)-callystatin A employing the SAMP/RAMP hydrazone alkylation methodology

[structure: see text] The asymmetric total synthesis of (-)-callystatin A has been achieved. The key steps generating the stereogenic centers rely on the asymmetric alpha-alkylation of aldehydes or ketones exploiting the SAMP/RAMP hydrazone alkylation methodology, as well as an enzymatic enantioselective reduction of a 3,5-dioxocarboxylate. For the construction of the alkene moieties, highly selective Wittig or Horner-Wadsworth-Emmons reactions were employed.     

A three-component Mannich-type reaction for selective tyrosine bioconjugation

A new selective bioconjugation reaction is described for the modification of tyrosine residues on protein substrates. The reaction uses imines formed in situ from aldehydes and electron-rich anilines to modify phenolic side chains through a Mannich-type electrophilic aromatic substitution pathway. The reaction takes place under mild pH and temperature conditions and can modify protein substrates at concentrations as low as 20 muM. Using an efficient fluorescence-based assay, we demonstrated the reaction using a number of aldehydes and protein targets. Importantly, proteins lacking surface-accessible tyrosines remained unmodified. It was also demonstrated that enzymatic activity is preserved under the mild reaction conditions. This strategy represents one of the first carbon-carbon bond-forming reactions for protein modification and provides an important complement to more commonly used lysine- and cysteine-based methods.     

2-D solid-state assay platform: a tool for screening aldehyde-releasing enzyme activity in colonies

A micro colony chip-based platform for high-throughput screening of proton releasing or oxygen consuming enzyme reactions was introduced recently. Here we present a new assay platform which allows screening for the release of aromatic and aliphatic aldehydes by enzymatic activity. The assay platform consists of 4-hydrazino-7-nitrobenzofurazane (NBD-H) as an indicator embedded in a soft, hydrophobic polymer matrix. NBD-H forms highly fluorescent products with aldehydes via hydrazone formation. The assay was characterized for various aliphatic and aromatic aldehydes and tested with two enzymatic reactions to show its potential. A transesterification reaction under water-free conditions with two esterase mutants and vinyl acetate as acyl donor leads to acetaldehyde as detectable product and a reaction under aqueous conditions with threonine aldolases. The substrates used are phenylserine, which forms benzaldehyde, and threonine, which forms acetaldehyde.     

Enzymatic Electrosynthesis of Alkanes by Bioelectrocatalytic Decarbonylation of Fatty Aldehydes

An enzymatic electrosynthesis system was created by combining an aldehyde deformylating oxygenase (ADO) from cyanobacteria that catalyzes the decarbonylation of fatty aldehydes to alkanes and formic acid with an electrochemical interface. This system is able to produce a range of alkanes (octane to propane) from aldehydes and alcohols. The combination of this bioelectrochemical system with a hydrogenase bioanode yields a H₂/heptanal enzymatic fuel cell (EFC) able to simultaneously generate electrical energy with a maximum current density of 25 μA cm^?2 at 0.6 V and produce hexane with a faradaic efficiency of 24 %.     

Intermolecular Cross-Acyloin Reactions by Fluoride-Promoted Additions of O-Silyl Thiazolium Carbinols

The addition of acyl anion equivalents to aliphatic aldehydes (crossed-acyloin reaction) has been developed. Cesium fluoride with isopropanol as solvent promotes the addition of O-silyl thiazolium carbinols to various aliphatic aldehydes in moderate to good yields. These reactions represent a general procedure for the selective coupling of aliphatic aldehydes by an acyl anion reaction which have been problematic until now.     

Lanthanoids in organic syntheses 7. selective reductions of carbonyl groups in aqueous ethanol solution.

Trivalent lanthanoid ions were shown to permit the selective reductions of conjugated aldehydes in the presence of non-conjugated ones. CrCl₃ is also effective in selective ketone reduction in the presence of aldehydes.     

N-Hydroxy-o-benzenedisulfonimide: A Misunderstood Selective Oxidizing Agent

N-Hydroxy-o-benzenedisulfonimide (now an easily accessible reagent) is a useful selective oxidizing agent; this is contrary to what was previously believed. The oxidation reactions of aldehydes to acids, benzyl alcohols to aldehydes, thiols to disulfides, and sulfides to sulfoxides were investigated (18 examples).     

Carbon-Nanotube-Appended PAMAM Dendrimers Bearing Iron(II) α-Keto Acid Complexes: Catalytic Non-Heme Oxygenase Models

Poly(amidoamine) dendrimers grafted on carbon nanotubes have been appended with iron(II)-α-keto acid (benzoylformate) complex of polypyridyl ligand to design artificial non-heme oxygenase model. This nano-enzyme was applied for selective catalytic oxidation of organic molecules. Although the carbon nanotubes serve as a robust heterogeneous platform, the amine terminals of dendrimers provide catalysts binding sites and the amide bonds provide a necessary second coordination sphere similar to the enzymatic polypeptide chains. Such a hybrid design prevented the deactivation of the primary active sites leading to 8 times faster oxidative decarboxylation rates than those of its homogeneous analogue. An electrophilic iron(IV)-oxo intermediate has been intercepted, which catalyzes the selective oxidation of alcohols to aldehydes and incorporates single oxygen atoms into sulfides and olefins by using aerial oxygen with multiple turnover numbers. The catalyst was consecutively regenerated three times by mild chemical treatment and showed negligible loss of activity.     

High-throughput synthesis and analysis of acylated cyanohydrins

The yields and optical purities of products obtained from chiral Lewis acid/Lewis base-catalysed additions of alpha-ketonitriles to prochiral aldehydes could be accurately determined by an enzymatic method. The amount of remaining aldehyde was determined after its reduction to an alcohol, whilst the two product enantiomers were analysed after subsequent hydrolysis first by the (S)-selective Candida antarctica lipase B and then by the unselective pig liver esterase. The method could be used for analysis of products obtained from a number of aromatic aldehydes and aliphatic ketonitriles. Microreactor technology was successfully combined with high-throughput analysis for efficient catalyst optimization.     

Fluoroalkyl alpha,beta-unsaturated imines. Valuable synthetic intermediates from primary fluorinated enamine phosphonates

[reaction: see text] A simple method for the preparation of fluoroalkyl allylamines or alpha,beta-unsaturated ketones by an olefination reaction of primary enamine phosphonates and aldehydes, followed by selective reduction with hydrides or hydrolysis, is reported. Fluorinated beta-amino nitriles are also obtained by an olefination reaction of primary enamine phosphonates with aldehydes and subsequent addition of metalated acetonitrile.     

Direct Observation of Radical Intermediates While Investigating the Redox Behavior of Thiamin Coenzyme Models

The redox behavior of “active aldehydes” 1 ⁻ derived from 3-benzylthiazolium salts and simple aldehydes in the presence of a base has been examined with low-temperature cyclic voltammetry and EPR spectroscopy. The highly negative oxidation potentials of 1 ⁻ and the spin distribution of the intermediate radicals 1 ^. indicate that the active aldehyde can act as an efficient electron mediator in thiamin-dependent enzymatic redox systems.     

Supported aqueous-phase enzymatic catalysis in organic media

The use of partially hydrated porous silica particles has been studied as a support for cofactor-dependent enzymatic catalysis in organic solvents. At an optimal pore hydration corresponding to 70% pore volume, horse liver alcohol dehydrogenase catalyzes the oxidation and reduction of alcohols and aldehydes, respectively, with rates sixfold higher than with nonporous glass beads as the enzymatic support and with cofactor recycling numbers in excess of 10⁵. Thus, supported aqueous-phase enzymatic catalysis makes highly effective use of the enzyme and cofactor by coimmobilization and by providing a high interfacial area for reactions in organic media.     

Iridium‐Catalyzed Formyl‐Selective Deuteration of Aldehydes

We report the first direct catalytic method for formyl‐selective deuterium labeling of aromatic aldehydes under mild conditions, using an iridium‐based catalyst designed to favor formyl over aromatic C−H activation. A good range of aromatic aldehydes is selectively labeled, and a one‐pot labeling/olefination method is also described. Computational studies support kinetic product control over competing aromatic labeling and decarbonylation pathways.     

Highly Selective Barbier‐Type Propargylations and Allenylations Catalyzed by Titanocene(III)

The alkyne functional group is found in many bioactive natural products and is the key to many important chemical transformations developed over recent years. Moreover, allenes have recently gained relevance as versatile reagents in organic synthesis. Mild, catalytic methods to enable the selective introduction of either alkyne or allene motifs into organic molecules are very valuable but, as yet, quite scarce. We describe an extremely mild and selective method for either the propargylation or allenylation of carbonyl compounds catalyzed by the abundant, safe, and inexpensive metal titanium. These reactions can selectively provide homopropargylic alcohols from aldehydes and ketones or α‐hydroxy‐allenes from aldehydes. The mechanisms involved were also investigated.     

PHOSPHORUS PENTOXIDE-MONTMORILLONITE K-10 AS CATALYST FOR THE PREPARATION OF 1,1-DIACETATES UNDER SOLVENT-FREE CONDITIONS

A facile and efficient method for the preparation of 1,1-diacetates of aldehydes is improved. P₂O₅/montmorillonite K10 catalyzed 1,1-diacetates formation from aldehydes in dry media. Both aromatic and aliphatic aldehydes gave high yields (70–95%) of the corresponding 1,1-diacetates. Advantages of this method are the use of an inexpensive and selective catalyst, with high yields in simple operation and short reaction time under solvent-free conditions.     

Pyridinium bromochromate: a new and efficient reagent for bromination of hydroxy aromatics

Pyridinium bromochromate (PBC) has been used as an efficient and selective nuclear brominating agent for bromination of various substituted hydroxy-acetophenones, aldehydes and phenols.     

Alumina as an versatile catalyst for the selective acetalization of aldehydes

Alumina was found to be an effective and convenient catalyst for acetalization of aldehydes to the corresponding 1,3-dioxoranes and 1,3-dioxanes. It can be used for selective protection of only formyl group of ketoaldehydes.     

Bis(trimethylsilyl)chromate catalyzed oxidations of alcohols to aldehydes and ketones with periodic acid

A facile, selective and high yielding bis(trimethylsilyl) chromate (BTSC) catalyzed selective oxidation of alcohols to aldehydes and ketones with periodic acid is reported.     

Selective oxoammonium salt oxidations of alcohols to aldehydes and aldehydes to carboxylic acids

The oxidation of alcohols to aldehydes using stoichiometric 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in CH(2)Cl(2) at room temperature is a highly selective process favoring reaction at the carbinol center best able to accommodate a positive charge. The oxidation of aldehydes to carboxylic acids by 1 in wet acetonitrile is also selective; the rate of the process correlates with the concentration of aldehyde hydrate. A convenient and high yield method for oxidation of alcohols directly to carboxylic acids has been developed.     

Synthesis of triphenylmethylphosphonium chlorochoromate as a mild and selective reagent for oxidation of alcohols

Triphenylmethylphosphonium chlorochoromate was synthesized from triphenylmethyl bromide and chromium(VI) oxide in HCl 6 N and used as an efficient and selective reagent for oxidation of alcohols to their corresponding aldehydes or ketones derivatives in refluxing acetonitrile in good to excellent yields.