New Nitrilotriacetic Acid and Ethylenediaminetetraacetic Acid Nitro Derivatives for the Synthesis of Bifunctional and Trifunctional Chelating Agents

Dehydration of serine derivatives into didehydroamino acids and subsequent conjugate addition of nitromethane led to novel nitro derivatives of nitrilotriacetic acid and ethylenediaminetetraacetic acid. Straightforward transformations of these compounds allowed the synthesis of bifunctional and trifunctional metal‐chelating agents via an Henry reaction.     

In-line and real-time prediction of recombinant antibody titer by in situ Raman spectroscopy

The Food and Drug Administration's (FDA) process analytical technology (PAT) framework has been initiated to encourage drug manufacturers to develop innovative techniques in order to better understand their processes and institute high level quality control which allows action at any point in the manufacturing process. While Raman spectroscopy and chemometrics have been successfully used to predict concentration of conventional metabolites in cell cultures, it is really not the case for active substances. Thus, we propose, for the first time, an in-line and real-time prediction of recombinant antibody titer using an immersion probe link to a spectrometer without the tacking of samples. A good robustness of the method is observed on different culture batches and the contamination risk is drastically reduced which is an important issue in biotechnology manufacturing processes.     

Highly efficient and mild copper-catalyzed N- and C-arylations with aryl bromides and iodides

Mild, efficient, copper-catalyzed N-arylation procedures for nitrogen heterocycles, amides, carbamates, and C-arylation procedures for malonic acid derivatives have been developed that afford high yields of arylated products with excellent selectivity. The N-arylation of imidazole with aryl bromides or iodides was found to be greatly accelerated by inexpensive, air-stable catalyst systems, combining catalytic copper salts or oxides with a set of structurally simple chelating ligands. The reaction was shown to be compatible with a broad range of aryl halides, encompassing sterically hindered, electron-poor, and electron-rich ones, providing the arylated products under particularly mild conditions (50-82 degrees C). The lower limit in ligand and catalyst loading and the scope of Ullmann-type condensations catalyzed by complexes bearing those ligands with respect to the nucleophile class have also been investigated. Chelating Schiff base Chxn-Py-Al (1c) generates a remarkably general copper catalyst for N-arylation of pyrrole, indole, 1,2,4-triazole, amides, and carbamates; and C-arylation of diethyl malonate, ethyl cyanoacetate, and malononitrile with aryl iodides under mild conditions (50-82 degrees C). The new method reported here is the most successful to date with regard to Ullmann-type arylation of some of these nucleophiles.     

Total synthesis of mauritines A, B, C, and F: cyclopeptide alkaloids with a 14-membered paracyclophane unit

A unified strategy for the synthesis of mauritines A (5), B (6), C (7), and F (10) has been developed based on a key intramolecular nucleophilic aromatic substitution reaction (S(N)Ar) for the formation of the strained 14-membered paracyclophane. It was demonstrated that the outcome of the cycloetherification is independent of the stereochemistry of the peptide backbone and that both (1R)-16 and (1S)-16 cyclized smoothly to provide the corresponding macrocycle. On the other hand, dehydration of the secondary benzylic alcohol, via the phenylselenide intermediate, is configuration dependent. (1R)-25 underwent the two-step syn-elimination much more easily than (1S)-22. A modified reductive deamination procedure via the diazonium intermediate was developed. A complete assignment of proton and carbon NMR spectroscopy signals for these natural products is reported for the first time.     

A general and mild Ullmann-type synthesis of diaryl ethers

[reaction: see text] An efficient method for the synthesis of diaryl ethers under particularly mild conditions is described. Inexpensive ligands were found to greatly accelerate the Ullmann-type coupling of aryl bromides or iodides with phenols. A series of diaryl ethers were obtained with excellent yields in acetonitrile in the presence of Cs(2)CO(3) and catalytic copper(I) oxide. The reaction tolerates substrates with unfavorable substitution patterns, such as sterically hindered coupling partners or electron-rich aryl halides.     

Synthesis, reactivity and stereochemistry of new phosphorus heterocycles with 5- or 6-membered rings

Syntheses of novel phosphorus heterocycles containing α-amino or α-hydroxyphosphonic or phosphinic acids motifs are developed. 2,3-dihydro-1,3-oxaphospholes (1) and 1,4,2-oxazaphosphinanes (2) exhibit a reactive part, respectively the enolether moiety and the P-H bond, which allows various structural modifications: (i) for 1a, by introduction of amino substituents, (ii) for 2a, by hydroxy- or aminoalkylation, by Michael addition or by P-arylation. These reactions present generally a good or even an excellent kinetic diastereoselectivity which can often be predicted by molecular models of the transition states.     

Triphenylphosphine catalyzed formation of functionalized 2‐aminothiophenes

Triphenylphosphine was used as a nucleophilic catalyst in the addition–cyclization reaction of phenyl isothiocyanate with electron‐deficient allenes. This strategy offers a new approach for the synthesis of 2‐aminothiophenes under neutral conditions. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:312–315, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20300     

A New Way for Potential Aminophosphonic Acids Precursors

Abstract

New five membered-ring 3,3-dihydro-1,4,2-oxazaphospholenes 1, potential precursors of aminophosphonic acids, have been synthesized and characterized by ¹H, ¹³C and ³¹P NMR.     

Chiral δ-Hydroxyalkyl Wittig Reagents: Synthesis and Reactivity

Abstract

enantioselective reduction of ketophosphonium salts give chiral synthons used in WITTIG reactions to prepare opticaly active ethylenic alcohols.