Christian G. Bochet

Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy

The review covers the knowledge on photoremovable protecting groups and includes all relevant chromophores studied in the time period of 2000–2012; the most relevant earlier works are also discussed.

Absolute configuration of chirally deuterated neopentane

The relationship between macroscopic chirality and chirality on the molecular level was unequivocally established in 1951 through anomalous X-ray scattering. Although this technique became the definitive method for determining the absolute configuration of a molecule, one important limitation of the approach is that the molecule must contain ‘heavy’ atoms (for example, bromine). The direct determination of absolute configurations for a wider range of molecules has recently become possible by measuring a molecule’s vibrational optical activity. Here we show that instrumental advances in Raman optical activity, combined with quantum chemical computations, make it possible to determine the absolute configuration of (R)-[2H1, 2H2, 2H3]-neopentane. This saturated hydrocarbon represents the archetype of all molecules that are chiral as a result of a dissymmetric mass distribution. It is chemically inert and cannot be derivatized to yield molecules that would reveal the absolute configuration of the parent compound. Diastereomeric interactions with other molecules, optical rotation, and electronic circular dichroism are, in contrast to the well-known case of bromochlorofluoromethane, not expected to be measurable. Vibronic effects in the vacuum ultraviolet circular dichroism might reveal that the molecule is chiral, but the presence of nine rotamers would make it extremely difficult to interpret the spectra, because the spatial arrangement of the rotamers’ nuclei resembles that of enantiomers. The unequivocal spectroscopic determination of the absolute configuration of (R)-[2H1, 2H2, 2H3]-neopentane therefore presented a major challenge, one that was at the very limit of what is possible.

Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

BACKGROUND Excitatory synapses in the CNS are highly dynamic structures that can show activity-dependent remodeling and stabilization in response to learning and memory. Synapses are enveloped with intricate processes of astrocytes known as perisynaptic astrocytic processes (PAPs). PAPs are motile structures displaying rapid actin-dependent movements and are characterized by Ca(2+) elevations in response to neuronal activity. Despite a debated implication in synaptic plasticity, the role of both Ca(2+) events in astrocytes and PAP morphological dynamics remain unclear. RESULTS In the hippocampus, we found that PAPs show extensive structural plasticity that is regulated by synaptic activity through astrocytic metabotropic glutamate receptors and intracellular calcium signaling. Synaptic activation that induces long-term potentiation caused a transient PAP motility increase leading to an enhanced astrocytic coverage of the synapse. Selective activation of calcium signals in individual PAPs using exogenous metabotropic receptor expression and two-photon uncaging reproduced these effects and enhanced spine stability. In vivo imaging in the somatosensory cortex of adult mice revealed that increased neuronal activity through whisker stimulation similarly elevates PAP movement. This in vivo PAP motility correlated with spine coverage and was predictive of spine stability. CONCLUSIONS This study identifies a novel bidirectional interaction between synapses and astrocytes, in which synaptic activity and synaptic potentiation regulate PAP structural plasticity, which in turn determines the fate of the synapse. This mechanism may represent an important contribution of astrocytes to learning and memory processes.

The ABC transporter BcatrB from Botrytis cinerea exports camalexin and is a virulence factor on Arabidopsis thaliana

Arabidopsis thaliana is known to produce the phytoalexin camalexin in response to abiotic and biotic stress. Here we studied the mechanisms of tolerance to camalexin in the fungus Botrytis cinerea, a necrotrophic pathogen of A. thaliana. Exposure of B. cinerea to camalexin induces expression of BcatrB, an ABC transporter that functions in the efflux of fungitoxic compounds. B. cinerea inoculated on wild-type A. thaliana plants yields smaller lesions than on camalexin-deficient A. thaliana mutants. A B. cinerea strain lacking functional BcatrB is more sensitive to camalexin in vitro and less virulent on wild-type plants, but is still fully virulent on camalexin-deficient mutants. Pre-treatment of A. thaliana with UV-C leads to increased camalexin accumulation and substantial resistance to B. cinerea. UV-C-induced resistance was not seen in the camalexin-deficient mutants cyp79B2/B3, cyp71A13, pad3 or pad2, and was strongly reduced in ups1. Here we demonstrate that an ABC transporter is a virulence factor that increases tolerance of the pathogen towards a phytoalexin, and the complete restoration of virulence on host plants lacking this phytoalexin.

Wavelength-Selective Caged Surfaces: How Many Functional Levels Are Possible?

The possibility of wavelength-selective cleavage of seven photolabile caging groups from different families has been studied. Amine-, thiol-, and carboxylic-terminated organosilanes were caged with o-nitrobenzyl (NVOC, NPPOC), benzoin (BNZ), (coumarin-4-yl)methyl (DEACM), 7-nitroindoline (DNI, BNI), and p-hydroxyphenacyl (pHP) derivatives. Caged surfaces modified with the different chromophores were prepared, and their photosensitivity at selected wavelengths was quantified. Different pairs, trios, and quartets of chromophore combinations with wavelength-selective photoresponse were identified. Our results show, for the first time, the possibility of generating surfaces with up to four different and independently addressable functional levels. In addition, this manuscript presents the first systematic comparison of the photolytic properties of different photolabile groups under different irradiation conditions.

Orthogonal Photolysis of Protecting Groups

The selective activation of photolabile protecting groups was made possible by the use of monochromatic light of suitable wavelength. This new approach allowed the orthogonal deprotection of a substrate containing several photosensitive groups.

Wavelength-selective cleavage of photolabile protecting groups

Abstract The selective photocleavage of protecting groups using monochromatic light is described. Some groups were found to react faster than others at 254 nm, whereas this trend was reversed at 419 nm. This behavior was preserved in solution mixtures of both groups. The selective control of which group is activated is thus achieved by using an influence external to the reaction mixture.

Diastereo- and enantioselective syntheses of (−)-coniine, (−)-solenopsin A, (−)-solenopsis fugaz venom and (−)-xenovenine via deoxygenative decarboxylation of 2-carbonylsultam-substituted n-hydroxy-piperidines and -pyrrolidines☆

Heating cyclic 2-carbonylsultam-substituted N-hydroxylamines 4 with NaH yields sultam auxiliary 8 and imines 10, which are trapped in situ either by i-Bu2AlH or organocerium reagents to give enantiomerically pure 2-mono- or trans-2,6(2,5)-disubstituted piperidines (pyrrolidines) 11 or 12.

Design of luminescent building blocks for supramolecular triple-helical lanthanide complexes

The ligand 2,6-bis(1′-ethyl-5′-methylbenzimidazol-2′-yl)pyridine (L5) reacts with lanthanide perchlorate in acetonitrile to give the mononuclear triple-helical complexes [Ln(L5)3]3+(Ln = Eu, Gd or Tb). The crystal structure of [Eu(L5)3][ClO4]3·4MeCN has been determined, which shows three unco-ordinated perchlorate anions and an [Eu(L5)3]3+ cation where the three tridentate ligands are wrapped around a pseudo-C3 axis. The co-ordination sphere around EuIII may be best described as a slightly distorted trigonal-tricapped prism where the six benzimidazole nitrogen atoms occupy the vertices of the prism and the three pyridine nitrogen atoms occupy the capping positions. A detailed geometrical analysis showed that the ethyl groups in L5 produce a slide of the strands which is responsible for the distortion of the triple-helical structure as exemplified by the low symmetry for the EuIII site in the luminescence spectra of [Eu(L5)3]3+. Proton NMR spectra in acetonitrile indicate that the triple-helical structure is maintained for [Ln(Li)3]3+{Ln = Eu or Tb; L = 2,6-bis(1′-R-benzimidazol-2′-yl)pyridine [R = Me L1, Et L2, Pr L3 or CH2C6H3(OMe)2-3,5 L4] or L5} on the NMR time-scale, but the stability of the complexes together with the structural arrangement of the ligands depend on the size of the substituents bound to the benzimidazole nitrogen atoms. Photophysical studies of [Eu(Li)3]3+ show that these steric effects affect the quantum yield in solution and that methyl groups bound to the 5 positions of the benzimidazole rings in L5 shift the π→π* transitions centred on the ligand, but do not strongly modify the emission properties of [Eu(L5)3]3+. Extended Huckel calculations give a qualitative insight into the factor controlling the π→π* transitions of the ligands and complexes.

The arene-alkene photocycloaddition

Summary In the presence of an alkene, three different modes of photocycloaddition with benzene derivatives can occur; the [2 + 2] or ortho, the [3 + 2] or meta, and the [4 + 2] or para photocycloaddition. This short review aims to demonstrate the synthetic power of these photocycloadditions.