Cinchona based squaramide catalysed enantioselective Michael addition of α-nitrophosphonates to aryl acrylates: enantioselective synthesis of quaternary α-aminophosphonates

Several cinchona based squaramide catalysts were applied to the asymmetric Michael addition of α-nitroethylphosphonates to acrylic acid aryl esters, resulting in high yields and enantioselectivities. The absolute configuration of one of the quaternary α-nitrophosphonate adducts was deduced from its experimental and calculated CD spectra. The adducts were reduced to their cyclic aminophosphonates by catalytic hydrogenation.     

Scope and Limitation for the Reaction of α,β-Unsaturated Carbonyl Compounds with Phosphorus Nucleophiles by Determination of the Half-Wave Potential

Abstract

During the formation of oxaphospholenes the phosphorus in the reagent gets oxidized and the double bond in the enones gets reduced.     

DIHALOCARBENE ADDITION TO ARYLSUBSTTTUTED VINYL PHOSPHATES UNDER PHASE TRANSFER CATALYTIC CONDITIONS

Abstract

Dihalocarbene addition to aryl-substituted vinyl phosphates was carried out both in solid-liquid and in liquid-liquid two phase systems. The dihalocyclopropane adducts of vinyl phosphates could be obtained in better yield using dihalocarbenes generated by the latter method and no hydrolysis of the vinyl phosphate and of the adduct occurred under these circumstances. Eighteen new vinyl phosphate-dihalocarbene adducts were synthetized and characterized.     

Reaction of Phosphoramides with Isocyanates in PTC Conditions - Novel Method of Synthesis of Carbodiimides

Abstract

During our attempts to prepare asymmetrically substituted carbodiimides of biochemical interest we have observed that phosphoramidate-esters react under phase-transfer conditions with isocyanates giving carbodiimides.     

Cyclopentadienyl(iron)arene-bis-(p-N,N-dimethylaminobenzylidene)-cyclopentanone Photoinitiated Polymerization of Methyl Methacrylate and Styrene

Abstract

Polymerization of methyl methacrylate and styrene can be effectively photoinitiated by a binary photoinitiator system consisting of cyclopentadienyl(iron)arene hexafluorophosphonate salt and bis(p-N, N-dimethylaminobenzylidene)cyclopentanone in the spectral range of 400–500 nm. The amine-type radical formed from the exciplex of the binary photoinitiator system is probably responsible for the radical polymerization of vinyl monomers. A probable mechanism of initiation of polymerization is discussed.     

Theoretical prediction of the protein–protein interaction between Arabidopsis thaliana COP1 and UVR8

In plants, ultraviolet-B radiation (280–315 nm) regulates gene expression and plant morphology through the UV RESPONSE LOCUS 8 (UVR8) photoreceptor. The first signaling event after quantal absorbance is the interaction of the UVR8 C-terminus with the E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1). The nature of the interaction between these two proteins is hitherto unknown. A protein homology model of the Arabidopsis thaliana COP1 seven-bladed propeller WD40 repeat domain and de novo folds of the C-terminal 27 amino acid (amino acids 397–423) peptide of Arabidopsis UVR8 (UVR8^397?423) is herein reported. Using a theoretical computational docking protocol, the interaction between COP1 and UVR8 was predicted. A core motif was identified in UVR8^397?423 comprising adjacent hydrophobic residues V410 and P411 together with a charged residue D412, homologous to corresponding motifs in other COP1-binding proteins, such as ELONGATED HYPOCOTYL 5 (HY5), cryptochrome 1 (CRY1), and salt tolerance proteins STO/STH. The protein–protein interaction between the COP1 WD40 repeat domain and UVR8^397?423 reveals binding within a region of COP1 overlapping with the binding site for HY5 and the other COP1-interacting proteins. This study provides a framework for understanding docking between UVR8 and COP1, which in turn gives clues for experimental testing of UVR8/COP1 interaction.     

A quantitative LC/MS method targeting urinary 1-methyl-4-imidazoleacetic acid for safety monitoring of the global histamine turnover in clinical studies

Anaphylaxis is a potentially life-threatening condition triggered mainly by the release of inflammatory mediators, notably histamine. In pharmaceutical research, drug discovery, and clinical evaluation, it may be necessary to accurately assess the potential of a compound, event, or disorder to promote the release of histamine. In contrast to the measurement of plasma histamine, determination of the stable metabolite 1-methyl-4-imidazoleacetic acid (tele-MIAA) in urine provides a noninvasive and more reliable methodology to monitor histamine release. This study presents a repeatable high-performance liquid chromatography coupled to electrospray mass spectrometry (LC–ESI–MS) method where tele-MIAA is baseline separated from its structural isomer 1-methyl-5-imidazoleacetic acid (pi-MIAA) and an unknown in human urine. The ion-pairing chromatography method, in reversed-phase mode, based on 0.5 mM tridecafluoroheptanoic acid demonstrated high repeatability and was applied in a clinical development program that comprised a large number of clinical samples from different cohorts. The inter- and intra-run precision of the method for tele-MIAA were 8.4 and 4.3 %, respectively, at the mean urinary concentration level, while method accuracy was between ?16.2 and 8.0 % across the linear concentration range of 22–1,111 ng mL^?1. Overall, method precision was greater than that reported in previously published methods and enabled the identification of gender differences that were independent of age or demography. The median concentration measured in female subjects was 3.0 μmol mmol^?1 of creatinine, and for male subjects, it was 2.1 μmol mmol^?1 of creatinine. The results demonstrate that the method provides unprecedented accuracy, precision, and practicality for the measurement of tele-MIAA in large clinical settings.

Neo‐Fused Hexaphyrin: A Molecular Puzzle Containing an N‐Linked Pentaphyrin

The first neo‐confused hexaphyrin(1.1.1.1.1.0) was synthesized by oxidative ring closure of a hexapyrrane bearing two terminal “confused” pyrroles. The new compound displays a folded conformation with a short interpyrrolic C???N distance of 3.102 Å, and thus it readily underwent ring fusion to afford a neo‐fused hexaphyrin with an unprecedented 5,5,5,7‐tetracyclic ring structure. Furthermore, coordination of Cu^II triggered a ring opening/contracting reaction to afford a Cu^II complex of an N‐linked pentaphyrin derivative. The roles of reactive N? C bonds in the porphyrinoid macrocycles were demonstrated.