Cyclizations to new azolopyridazines and related ring systems

In the course of our recent synthetic activity in the area of ring closure reactions we have found that relatively little had been published on azolopyridazines and related compounds, and this circumstance prompted us to explore novel pathways to such ring systems. In the present short review three such approaches from our laboratory leading to various fused azoles are discussed.     

VIER- UND FÜNFGLIEDRIGE PHOSPHORHETEROCYCLEN,XVI 1.3.4.2Λ3-OXADIAZAPHOSPHOLINE

Abstract

Die Kondensation von N ¹-substituierten N-Acetyl-und-Benzoyl-hydrazinen mit P[N(CH₃)₂]₃ oder CH₃P[NCH₃)₂]₂ fuhrt stets zu 3-substituierten 1.3.4.2Λ³-Oxadizaphospholinen, auch wenn der jeweilige Substituent die Bildung von anderen isomeren Fünfringen oder von Isomeren mit größerem Ring oder eine weitergehende Kondensation zuließe. Sie können in die 2.2-Dichloro- und 2-Thioxo-1.3.4.2Λ⁵-Oxadiazaphospholine übergeführt werden.

Condensation of N ¹-substituted N-acetyl and N-benzoyl hydrazines with P[N(CH₃)₂]₃ or CH₃P[N(CH₃)₂] 2 always gives 3-substituted 1.3.4.2Λ3-oxadiazaphospholines, even if the substituent would allow other isomeric five membered or larger ring phosphorus heterocycles to be formed, or the condensation to proceed further. The title compounds can be oxidized to 2.2-dichloro and 2-thioxo 1.3.4.2Λ⁵-oxadiazaphospholines.     

New approach for the synthesis of 3H-pyrrolo[2,3-c]isoquinoline derivatives

Synthesis of new 2,3-diaryl-3H-pyrrolo[2,3-c]isoquinoline derivatives has been elaborated starting from isoquinoline-3-amine. Buchwald–Hartwig arylation and subsequent iodination in position 4 afforded 3-arylamino-4-iodoisoquinolines. These compounds were subjected to Sonogashira cross-coupling reactions with some selected acetylenes, and the resulting coupled products underwent cyclization in the presence of tetrabutylammonium fluoride to give title derivatives.     

Prospects of open charm production at GSI-FAIR and J-PARC

We present a detailed phenomenological study of the prospects of open charm physics at the future p̄p and pp facilities GSI-FAIR and J-PARC, respectively. In particular, we concentrate on the differential cross sections and the charge and longitudinal double-spin asymmetries at next-to-leading order accuracy. Theoretical uncertainties for the proposed observables are estimated by varying the charm quark mass and the renormalization and factorization scales. PACS 12.38.Bx; 13.88.+e     

Synthesis and ring transformation of novel tetracyclic fused as-triazines

Summary Eight new tetracyclic fused as-triazines (4–6,8,11–13, and15) have been synthesized by conversion and subsequent ring transformation of 1,2-diaminoisoquinolinium (2) and -quinolinium salts (9) with 4-benzoyl-5-phenylfuran-2,3-dione (1). Selective alkylations of the new products revealed that these reactions are governed mainly by the electronic density of the lone pairs as well as by steric effects.Dedicated to em. Univ. Prof. Dr. E. Ziegler on the occasion of his 80th birthday     

Über einige Derivate der Aminoxyessigsäure

Zusammenfassung Es werden Derivate der Aminoxyessigsäure^*, die sich durch Abwandlung der Carboxyl- und Aminoxygruppe ergeben, beschrieben. Der Abbau der Isopropylidenaminoxyessigsäure nachCurtius ergibt das Isopropylidenaminoxy-methyl-isocyanat, das sich in üblicher Weise mit Aminen und Alkoholen umsetzen läßt Es wird gezeigt, daß Isopropyliden-aminoxyacetylchlorid zur Herstellung von längerkettigen Aminoxyverbindungen herangezogen werden kann.     

Experimental design considerations in quantification experiments by using the internal standard technique: cholesterol determination by gas chromatography as a case study

An overview on experimental design in quantification experiments using the internal standard technique is described. Particular emphasis is given to the modelling of the relationship analyte/internal standard and the estimation of the optimal amount of internal standard to be used throughout the analytical concentration range by using a uniform shell design with a minimum number of seven experiments. The described approach is demonstrated in the analysis of cholesterol in various reference materials by gas chromatography (GC), using alpha-5 cholestan as internal standard. The outlined approaches can be applied in the determination of any kind of analyte.     

Drug Design Inspired by Nature: Crystallographic Detection of an Auto‐Tailored Protease Inhibitor Template

De novo drug discovery is still a challenge in the search for potent and selective modulators of therapeutically relevant target proteins. Here, we disclose the unexpected discovery of a peptidic ligand 1 by X‐ray crystallography, which was auto‐tailored by the therapeutic target MMP‐13 through partial self‐degradation and subsequent structure‐based optimization to a highly potent and selective β‐sheet peptidomimetic inhibitor derived from the endogenous tissue inhibitors of metalloproteinases (TIMPs). The incorporation of non‐proteinogenic amino acids in combination with a cyclization strategy proved to be key for the de novo design of TIMP peptidomimetics. The optimized cyclic peptide 4 (ZHAWOC7726) is membrane permeable with an IC₅₀ of 21 nm for MMP‐13 and an attractive selectivity profile with respect to a polypharmacology approach including the anticancer targets MMP‐2 (IC₅₀: 170 nm ) and MMP‐9 (IC₅₀: 140 nm ).     

Crossover from a molecular Bose-Einstein condensate to a degenerate Fermi gas

We demonstrate a reversible conversion of a 6Li2 molecular Bose-Einstein condensate to a degenerate Fermi gas of atoms by adiabatically crossing a Feshbach resonance. By optical in situ imaging, we observe a smooth change of the cloud size in the crossover regime. On the Feshbach resonance, the ensemble is strongly interacting and the measured cloud size is 75(7)% of the one of a noninteracting zero-temperature Fermi gas. The high condensate fraction of more than 90% and the adiabatic crossover suggest our Fermi gas to be cold enough to form a superfluid.