Stereoselective synthesis of unnatural α-amino acid derivatives through photoredox catalysis

A protocol for stereoselective C-radical addition to a chiral glyoxylate-derived N-sulfinyl imine was developed through visible light-promoted photoredox catalysis, providing a convenient method for the synthesis of unnatural α-amino acids. The developed protocol allows the use of ubiquitous carboxylic acids as radical precursors without prior derivatization. The protocol utilizes near-stoichiometric amounts of the imine and the acid radical precursor in combination with a catalytic amount of an organic acridinium-based photocatalyst. Alternative mechanisms for the developed transformation are discussed and corroborated by experimental and computational studies.

A protocol for stereoselective C-radical addition to a chiral glyoxylate-derived N-sulfinyl imine was developed through visible light-promoted photoredox catalysis, providing a convenient method for the synthesis of unnatural α-amino acids.     

Modelling and mutation studies on the histamine H1-receptor agonist binding site reveal different binding modes for H1-agonists: Asp116 (TM3) has a constitutive role in receptor stimulation

Summary A modelling study has been carried out, investigating the binding of histamine (Hist), 2-methylhistamine (2-MeHist) and 2-phenylhistamine (2-PhHist) at two postulated agonistic binding sites on transmembrane domain 5 (TM5) of the histamine H₁-receptor. For this purpose a conformational analysis study was performed on three particular residues of TM5, i.e., Lys²⁰⁰, Thr²⁰³ and Asn²⁰⁷, for which a functional role in binding has been proposed. The most favourable results were obtained for the interaction between Hist and the Lys²⁰⁰/Asn²⁰⁷ pair. Therefore, Lys²⁰⁰ was subsequently mutated and converted to an alanine, resulting in a 50-fold decrease of H₁-receptor stimulation by histamine. Altogether, the data suggest that the Lys²⁰⁰/Asn²⁰⁷ pair is important for activation of the H₁-receptor by histamine. In contrast, analogues of 2-PhHist seem to belong to a distinct subclass of histamine agonists and an alternative mode of binding is proposed in which the 2-phenyl ring binds to the same receptor location as one of the aromatic rings of classical histamine H₁-antagonists. Subsequently, the binding modes of the agonists Hist, 2-MeHist and 2-PhHist and the H₁-antagonist cyproheptadine were evaluated in three different seven--helical models of the H₁-receptor built in homology with bacteriorhodopsin, but using three different alignments. Our findings suggest that the position of the carboxylate group of Asp¹¹⁶ (TM3) within the receptor pocket depends on whether an agonist or an antagonist binds to the protein; a conformational change of this aspartate residue upon agonist binding is expected to play an essential role in receptor stimulation.Abbreviations 2-MeHist 2-methylhistamine - 2-PEA 2-pyridyl-ethylamine - 2-PhHist 2-phenylhistamine - CHO Chinese hamster ovary - E_int interaction energy - E_str strain energy - GES global energy structure - gpH₁R guinea pig H₁-receptor - GPCR G-protein coupled receptor - Hist histamine - N proximal nitrogen - N tele nitrogen - TM transmembrane domain - WT wild type     

A new approach for the synthesis of fused pyrroles. The synthesis of acyl substituted pyrrolo[1,2-x]azines

N-Acetonyl- and N-phenacyl quaternary salts of α-methyl substituted heterocycles 16, 17, 21, 23 and 26 were converted with DMFDMA into the corresponding 3-acylpyrrolo[1,2-a]pyridine 18 , 7-benzoylpyrrolo-[1,2-c]pyrimidine 22 , and 6-benzoylpyrrolo[1,2-a]pyrazine derivatives 24 and 27 . A concurrent reaction produced methyl and phenyl substituted pyrrolo[1,2-x]azines 19, 20, 25 and 28 .     

Acidité dans le nitrométhane: III. Détermination électrochimique de la basicité du nitrométhane — Corrélation Dn/Eo(Hs+/H2/

The use of the complex acid HAlCl₄ (HCl+AlCl₃) permits the detemrination of the standard potential of the hydrogen electrode in nitromethane. The result (E₀(H_s⁺/H₂)=0.5 V vs. Fc/Fc⁺, Fc=ferrocene) shows that nitromethane is very weakly basic. This measurement is confirmed by showing that the standard potential of the hydrogen electrode in various solvents is linked to Gutmann's donor numbers of these solvents. The E₀(H_s⁺/H₂) value obtained in nitromethane belongs to the correlation line.     

Carbon-13 spectra of some tetrahydropyridines. The structure of the tetrahydropyridines from 3,5-lutidine 1-oxide and mercaptans in acetic anhydride

The reaction of 3,5-lutidine 1-oxide ( 1 ) with t-butyl mereaptan in acetic anhydride, with or without triethylamine, was reinvestigated. There was obtained 2-t-butylthio-3,.5-lutidine as the major product, a small quantity of 3-(t-bulylthio)methyl-5-picoline, 1-acetyl-2,3-diacetoxy-3,5-dirnethyl-6-t-butylthio-1,2,3,6-tetrahydropyridine (which represents a structure revision) and l-acetyl-2,6-dihydroxy-3-t-butylthio-3,5-dimethyl-1,2,3,6-tetrahydropyridine. A similar reaction of 1 with 1-adamantyl mercaptan furnished 2-(l-adamantylthio)-3,5-lutidine and 1-acetyl-2,3-diacetoxy-3,5-dimethyl-6-(1-adamantylthio)-1,2,3,6-tetrahydropyridine. The structures of these new tetrahydropyridines were established primarily by carbon-13 nmr spectra.     

Negatively charged hyperbranched polyether-based polyelectrolytes

The preparation of carboxylated hyperbranched polyglycerols of narrow polydispersity was achieved by modification (78–90%) of the hydroxyl end groups via Michael addition of acrylonitrile, followed by hydrolysis. High conversion could only be achieved for low molecular weight starting materials (520 and 1,030 g mol⁻¹). The solution properties of the resulting materials were investigated by dynamic light scattering (DLS), showing the formation of large aggregates with size depending on the pH value. After deposition on a negatively charged mica surface, the structures observed by atomic force microscope (AFM) show the coexistence of aggregates and single macromolecules. Most interesting, in the case of the lower molecular weight sample (PG 520 g mol⁻¹), extended and ordered terrace structures were formed, which are unprecedented for hyperbranched polymers and are of interest for surface modification in general.     

v---v pumping in H2: estimate of induced dissociation at 300°K

By means of the stimulated Raman effect one may produce in H₂, D₂, and in several other gases, a substantial population in the ν = 1 state. Subsequent to the pulse excitation v---v energy transfers rapidly generate a vibrational distribution which is approximately equivalent to (3–4) × 10³°K. Then, in H₂ + D₂ mixtures metathetic reactions occur. Here we report on a computer simulation of an experiment described elsewhere, designed to estimate whether a measurable fraction of the hydrogen molecules reach the upper vibrational level and dissociate. Solutions of the coupled differential equations show that the anticipated hydrogen atom concentrations are too low by a factor of 10⁷-10⁸ to account for the observed H/D exchanges. These calculations also show that the conventional phenomenological rate equation for dissociation does not apply to this highly non-thermal distribution.     

Über die Konstitution eines Nebenalkaloides aus Adhatoda vasica Nees

Zusammenfassung Das in der vorangehenden Mitt. vonE. Späth undF. Gandini-Kesztler beschriebene Nebenalkaloid wird auf synthetischem Wege mit dem 6-Hydroxy-peganin identifiziert. Die phenolische OH-Gruppe steht also, bezogen auf Formel III, nicht an der Stelle, welche dem CH₃O des Harmins entspricht.     

LETTUCE SEED GERMINATION: EFFECTS OF HIGH TEMPERATURE AND OF REPEATED FAR-RED TREATMENT IN RELATION TO PHYTOCHROME

Abstract— At 37°C the active form of phytochrome in lettuce seed cannot function to promote subsequent germination. This effect of high temperature is distinct from thermal acceleration of dark reversion from the active form of phytochrome to the inactive form, and may be due to reversible denaturation of phytochrome.
Repeated brief irradiations with far-red light inhibit subsequent germination in the whole seed, whereas a similar irradiation regime results in a strong enhancement of the development of growth potential (ability to expand against an externally-imposed osmotic restraint) in the excised axial portion of the seed. A possible explanation for these two opposing results, in volving two different pigment systems with effective loci in different parts of the seed, is suggested.     

Umsetzung von Metall- und Metalloidverbindungen mit mehrfunktionellen Molekülen,XIX. Synthese von Amidoborazinen

Reaction of Metal and Metalloid Compounds with Polyfunctional Molecules. XIX. Synthesis of Amidoborazines By reaction of 2-chloro-1,3,4,5,6-pentamethylborazin with silylated carbonic acid amides and thioamides resp. the corresponding amidoborazines are obtained. By reaction of lithiated hexamethyldisilazane with 2-chloro-1,3,4,5,6-pentamethylborazine, the 2-hexamethyldisilazanyl-1,3,4,5,6-pentamethylborazine is formed. ¹H, ¹¹B, and ¹⁹F n.m.r. spectra, mass spectra and characteristic i.r. group frequencies are reported.