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.     

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.     

Die analytische Fortsetzung von AntennenimpedanzenZ(ν+jω) von der imaginären Achse in die positive Halbebeneν>0

A minimum principle for antenna impedances is established; contrary to a similar older variational principle, it furnishes lower limits forZ(ν) instead of upper limits. By means of these variational principles properties of the antenna impedance can be derived with little effort forp=ν>0 andp=jω. A new proof is given for a formula relating the impedance of a free radiating dipole to the impedance of the same dipole when enclosed in a distant reflecting shell.     

Selectivity of methylation of some new [1,2,3]triazolo[4,5-d]pyridazines and structure elucidation by H–N NMR spectroscopy

Alkylation of some selected [1,2,3]triazolo[4,5-d]pyridazines having five or more nitrogen atoms capable for alkylation was investigated. Pyridyl derivatives substituted also on the [1,2,3]triazole ring gave quaternary pyridinium salts, whereas in the case of the analogues compounds unsubstituted at the triazole moiety, the alkylation of the triazole ring was also observed. Unambiguous structure elucidation was provided by ¹H–¹⁵N HMBC experiments which also allowed the assignment of the ¹⁵N NMR shifts.     

Synthesis of 5H-pyridazino[4,5-b]indoles and their benzofurane analogues utilizing an intramolecular Heck-type reaction

The title ring systems were prepared from pyridazin-3(2H)-one precursors in novel, efficient pathways. 2-Methylbenzo[b]furo[2,3-d]pyridazin-1(2H)-one was synthesized via a regioselective nucleophilic substitution reaction of a 2-methyl-4,5-dihalopyridazin-3(2H)-one with phenol followed by an intramolecular Heck-type reaction. The same molecule and its 6-phenyl analogue were also prepared via reaction of 2-methyl-5-iodopyridazin-3(2H)-one or 2-methyl-5-chloro-6-phenylpyridazin-3(2H)-one, respectively, with 2-bromophenol or 2-iodophenol followed by Pd-catalyzed cyclodehydrohalogenation. Moreover, a new approach for the synthesis of 2-methyl-2,5-dihydro-1H-pyridazino[4,5-b]indol-1-ones was also elaborated utilizing a Heck-type ring closure reaction on 5-[(2-bromophenyl)amino]-2-methylpyridazin-3(2H)-ones which were obtained via Buchwald-Hartwig amination of 2-methyl-5-halopyridazin-3(2H)-ones with 2-bromoaniline.     

Über die Struktur der Acrylnitril-Guanidin-Kondensate Über Heterocyclen, 78. Mitt.

Repetition of the work ofSugino andTamaka ¹ showed that acrylonitrile and guanidine react inDMF to yield not only 3,4,6,7-tetrahydro-2H-pyrimido[1,2—a]pyrimidine-2,8(1H)-diimine (1), but a mixture (F) of1 (as a main product) and 2-amino-4-imino-1,4,5,6-tetrahydropyrimidine-1-propionitrile (7) besides one or two bases not identified so far.1 and7 were isolated as picrates. For the prove of their structures,1- and7-picrate were also prepared by an unequivocal synthesis starting from iminodipropionitrile hydrochloride8 · HCl: The latter on reaction with cyanamide gave9 which cyclized to afford a mixture of1,7 and 2-amino-4-oxo-1,4,5,6-tetrahydropyrimidine-1-propionitrile (10). The picrates of1 and7 were identical with those prepared from the acrylonitrileguanidine-condensateF. This result supports the prior proposed¹ structures of pyrimidopyrimidine1 and of4,5 and6, obtained by hydrolysis of1. Nmr-, ir-and some of the mass spectra of1,4,7–10 (and their salts) are reported.

     

Inverse gas chromatography study on partially esterified paper fiber

Paper fiber was treated in a heterogeneous esterification reaction with four different fatty acids. This fiber was used to strengthen polyethylene (PE) composites. Modified and unmodified cellulose fiber was characterized with inverse gas chromatography. In previous work, characterization was also carried with X-ray photoelectron spectroscopy (XPS), solid-state NMR, differential scanning calorimetry and thermogravimetry. Individual fibers were found to be covered with the corresponding esters (cellulose undecylenate, undecanoate, oleate, stearate) with partial degrees of substitution of the cellulose. Comparison of XPS and NMR results showed that the surface degree of substitution of the cellulose fiber was higher than for the bulk, showing that the esterification reaction was a surface phenomenon. The aim of this work was to acquire information on the surface characteristics of the fiber and to see whether it could be correlated to PE composite mechanical strength results. The conclusions are that polar probes seem to diffuse more into the fibers than the non-polar probes, as the non-polar component of the surface tension of the modified fiber is much lowered towards that of PE, while donor-acceptor characteristics are hardly changed by esterification. The ester with the lowest non-polar component of the surface energy, the oleate, also gives the composite with the best mechanical properties.