The application of (S)-1,10-binaphthyl-2,20-diol as NMR chiral solvating agent (CSA) for omeprazole, and three of its analogs (lanso-, panto-, and rabe-prazole) was investigated. The formation of diastereomeric host–guest complexes in solution between the CSA and the racemic substrates produced sufficient NMR signal splitting for the determination of enantiomeric excesses by Hor F-NMR spectroscopy. Using of hydrophobic deuterated solvents was mandatory for obtaining good enantiodiscrimination, thus suggesting the importance of intermolecular hydrogen bonds in the stabilization of the complexes. The method was applied to the fast quantification of the enantiomeric purity of in-process samples of S-omeprazole. Chirality 00:000–000, 2009. VC 2009

The assignment of absolute configuration by NMR

Tetrazine-based cycloadditions: application to pretargeted live cell imaging.

Nitric oxide has emerged as an important mammalian metabolic intermediate involved in critical physiological functions such as vasodilation, neuronal transmission, and cytostasis. Nitric oxide synthase (NOS) catalyzes the five-electron oxidation of L-arginine to citrulline and nitric oxide. Cosubstrates for the reaction include molecular oxygen and NADPH. In addition, there is a requirement for tetrahydrobiopterin. NOS also contains the coenzymes FAD and FMN and demonstrates significant amino acid sequence homology to NADPH-cytochrome P-450 reductase. Herein we report the identification of the inducible macrophage NOS as a cytochrome P-450 type hemoprotein. The pyridine hemochrome assay showed that the NOS contained a bound protoporphyrin IX heme. The reduced carbon monoxide binding spectrum shows an absorption maximum at 447 nm indicative of a cytochrome P-450 hemoprotein. A mixture of carbon monoxide and oxygen (80%/20%) potently inhibited the reaction (73-79%), showing that the heme functions directly in the oxidative conversion of L-arginine to nitric oxide and citrulline. Additionally, partially purified NOS from rat cerebellum was inhibited by CO, suggesting that this isoform may also contain a P-450-type heme. NOS is the first example of a soluble cytochrome P-450 in eukaryotes. In addition, the presence of FAD and FMN indicates that this is the first catalytically self-sufficient mammalian P-450 enzyme, containing both a reductase and a heme domain on the same polypeptide.

Nitric oxide synthase is a cytochrome P-450 type hemoprotein

Diels-Alder reactions of azadienes

Acetogenins from Annonaceae: recent progress in isolation, synthesis and mechanisms of action

Syntheses and evaluation of pyridazine and pyrimidine containing bioisosteres of (+/-)-pyrido[3.4-b]homotropane and pyrido-[3.4-b]tropane as novel nAChR ligands.

Cycloadditionsreaktionen von Oxepin (1) mit dem Tetrazin 3 oder dem Triazin 12 fuhren zum Dihydrooxepino[4,5-d]pyridazin 5 bzw. Oxepino[4,5-c]pyridin 13 via [2 + 4]-Cycloaddition und zum Phthalazin 9 bzw. Isochinolin 14 sehr wahrscheinlich via [6 + 4]-Cycloaddition. Mit 2,7-Dimethyloxepin (15) erhalt man im Gegensatz dazu lediglich die Reaktionsprodukte 16 und 20, die aus der [2 + 4]-Cycloaddition resultieren. Durch Oxidation von 16 mit Silber(I)-oxid entsteht das Oxepino[4,5-d]pyridazin 17, das in Salzsaure ebenso wie 20 umgelagert wird in das Pseudoazulen 19 bzw. 21.



[4 + 2] Cycloadditions with Inverse Electron Demand, XVII. Oxepin and 2,7-Dimethyloxepin as Dienophiles in Diels-Alder Cycloadditions with Inverse Electron Demand



The cycloaddition reactions of oxepin (1) with the tetrazine 3 and the triazine 12 yield the dihydrooxepino[4,5-d]pyridazine 5 and the oxepino[4,5-c]pyridine 13, resp., via [2 + 4] cycloaddition as well as the phthalazine 9 and the isoquinoline 14, resp., most probably via [6 + 4] cycloaddition. On the contrary, 2,7-dimethyloxepin (15) only gives the products 16 and 20, which result from [2 + 4] cycloaddition. Oxidation of 16 by silver(I) oxide leads to the oxepino[4,5-d]pyridazine 17, which as well as 20 in hydrochloric acid rearranges to the pseudoazulenes 19 and 21, resp.

[4 + 2]-Cycloadditionen mit inversem Elektronenbedarf, XVII. Oxepin und 2,7-Dimethyloxepin als Dienophile bei Diels-Alder-Cycloadditionen mit inversem Elektronenbedarf

„Inverse” Diels-Alder-Additionen, 4. Mitt.: π-Elektronenreiche, benzokondensierte Heteroaromaten als „inverse” Dienophile

15N NMR Studies of the Tautomeric Equilibrium of N-Monosubstituted Amidines and of N,N′-Diphenylguanidine



15N NMR data are reported for tautomeric N-monosubstituted amidines 1a and b and for N,N′-diphenylguanidine (6). In order to elucidate the position of the tautomeric equilibrium, the nitrogen resonances of the salts of 1a, b and 6 were also determined. For comparison, chemical shifts δ15N were measured of non-tautomeric amidines 2 – 5. The preferred tautomers for N-phenylbenzamidine (1a) and for 6 have the CN double bond conjugated with the phenyl group. Replacement of an NH proton with an alkyl group, as in 1b, has little effect on the tautomeric equilibrium of amidines.

15N‐NMR‐Studien der Tautomerie in N‐monosubstituierten Amidinen und in N,N′‐Diphenylguanidin

Die chemischen Verschiebungen δ 15N und die Kopplungskonstanten 1J(15N, 1H) mehrerer 2-Hydroxyguanidine 1 und Amidoxime 4 wurden bestimmt. Die Strukturen und der Ort der Protonierung dieser Verbindungen werden diskutiert. Die Synthese 1-monosubstituierter 2-Hydroxyguanidine wurde verbessert.



15N NMR Studies of 2-Hydroxyguanidines and Amide Oximes



Chemical shifts δ 15N and coupling constants 1J(15N, 1H) have been determined for several 2-hydroxyguanidines 1 and amide oximes 4. Structures and protonation sites of these compounds are discussed. The synthesis of 1-monosubstituted 2-hydroxyguanidines has been improved.

Thomas Kämpchen

Papers

Syntheses and evaluation of pyridazine and pyrimidine containing bioisosteres of (+/-)-pyrido[3.4-b]homotropane and pyrido-[3.4-b]tropane as novel nAChR ligands.

[4 + 2]-Cycloadditionen mit inversem Elektronenbedarf, XVII. Oxepin und 2,7-Dimethyloxepin als Dienophile bei Diels-Alder-Cycloadditionen mit inversem Elektronenbedarf

„Inverse” Diels-Alder-Additionen, 4. Mitt.: π-Elektronenreiche, benzokondensierte Heteroaromaten als „inverse” Dienophile

15N‐NMR‐Studien der Tautomerie in N‐monosubstituierten Amidinen und in N,N′‐Diphenylguanidin

15N‐NMR‐Studien an 2‐Hydroxyguanidinen und Amidoximen