Wolfgang Holzer

Chemoselective Activation Strategies of Amidic Carbonyls towards Nucleophilic Reagents

Important advancements have been made in recent years in the development of chemoselective additions of nucleophiles to well known inert amide carbonyls in the presence of multi-electrophilic substrates. Herein, we present the most relevant results showing how carbonyl amides can be chemoselectively functionalised in the presence of electrophilic functionalities such as Weinreb amides.

Synthesis and evaluation of indole, pyrazole, chromone and pyrimidine based conjugates for tumor growth inhibitory activities - Development of highly efficacious cytotoxic agents

Based upon the lead compounds 10 and 11, a number of conjugates were synthesized by the combination of chromone-pyrimidine, chromone-indolinone, chromone-pyrazole, indole-pyrimidine, indole-indolinone and indole-pyrazole moieties. Evaluation of these compounds for tumor growth inhibitory activities over 60 human tumor cell lines provided highly efficacious compounds 15, 41, 43, 66, 69, and 72 with an average GI(50) over all the 60 human tumor cell lines as 3.2 μM, 3.1 μM, 1.7 μM, 2.6 μM, 50.1 μM and 2.0 μM, respectively.

Addition of lithium carbenoids to isocyanates: a direct access to synthetically useful N-substituted 2-haloacetamides.

The addition of lithium carbenoids to isocyanates provides a versatile access to N-substituted 2-haloacetamides: the reaction tolerates the presence of variously functionalized substituents on the nitrogen atom, including sterically demanding ones and reactive halogens. No erosion of the enantiopurity was observed in the case of optically active isocyanates. One of the substrates prepared has been employed in Charettes type chemoselective addition of a Grignard reagent to access an α-chloroketone.

An easy access to anomeric glycosyl amides and imines(Schiff bases) via transformation of glycopyranosyl trimethylphosphinimides

Abstract The preparation and application of anomeric glycosyl phosphinimides in preparative synthesis were studied. Starting from the appropriate glycosyl azides and trialkyl or triaryl phosphines, the corresponding phosphinimides were obtained by modified Staudinger reactions. The latter compounds were readily converted into 1- N -acyl-gluco- and galactopyranosyl amines with high yields by applying activated acid derivatives or simple carboxylic acids. 1- N -Alkylidene- or arylidenephosphinimines (Schiff bases) were obtained by means of aza-Wittig reactions using aliphatic or aromatic aldehydes, respectively.

Structures of Highly Twisted Amides Relevant to Amide N-C Cross-Coupling: Evidence for Ground-State Amide Destabilization.

Herein, we show that acyclic amides that have recently enabled a series of elusive transition-metal-catalyzed N-C activation/cross-coupling reactions are highly twisted around the N-C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N-glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α-carbon atom. The (15) N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground-state twist as a blueprint for activation of amides toward N-C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non-planar amide bonds.

Highly efficient chemoselective N-TBS protection of anilines under exceptional mild conditions in the eco-friendly solvent 2-methyltetrahydrofuran

A straightforward chemoselective protection of anilines as N-TBS derivatives is described by using a suitable deprotonation of the amine with methyllithium in the environmentally friendly and safer substitute of THF, 2-methyltetrahydrofuran, under exceptional mild reaction conditions (0 °C, 30 min). Interestingly, the protecting group maybe cleaved efficiently by simple treatment of N-TBS-anilines with silica gel in ethanol–water.

Pyridazines. IIIL: The configuration of novel thiosemicarbazone derivatives of pyridazinecarbaldehydes and alkyl pyridazinyl ketones

Determination de la structure et de la configuration des derives de thiosemicarbazones contenant un groupement pyridazinyl-3, pyridazinyl-4 ou pyridyl-2 par spectrometrie RMN 1 H et 13 C

Heterocyclic analogs of thioflavones: synthesis and NMR spectroscopic investigations.

The synthesis of several hitherto unknown heterocyclic ring systems derived from thioflavone is described. Coupling of various o-haloheteroarenecarbonyl chlorides with phenylacetylene gives 1-(o-haloheteroaryl)-3-phenylprop-2-yn-1-ones, which were treated with NaSH in refluxing ethanol to yield the corresponding bi- and tricyclic annelated 2-phenylthiopyran-4-ones. Detailed NMR spectroscopic investigations of the ring systems and their precursors are presented.

First Synthesis of 3-Acetyl-2-aminothiophenes Using the Gewald Reaction

Novel 3-acetyl-2-aminothiophenes were prepared from cyanoacetone and 1,4-dithianyl-2,5-diols using a modified Gewald reaction. The syntheses of the corresponding acetamides, as well as that of 3-acetyl-2-amino-5-nitrothiophene - an interesting building-block for thiophene azo dyes - are reported. Detailed spectroscopic investigations ((1)H-NMR, (13)C-NMR, MS, IR) of the obtained compounds are presented.

Convenient and rapid determination of the configuration of aldoximes and ketoximes by means of NOE difference spectroscopy

Abstract Based on a through-space connection observed between the hydroxyl proton and the iminyl proton or protons attached to the α-carbon atom in various types of oximes, homonuclear NOE difference spectroscopy utilizing d 6 -DMSO as solvent is proposed as a simple method for the elucidation of the stereochemistry.