Fluorinated Vinylsilanes from the Copper-Catalyzed Defluorosilylation of Fluoroalkene Feedstocks.

Herein, a copper-catalyzed C-F bond defluorosilylation reaction of tetrafluoroethylene and other polyfluoroalkenes is described. Mechanistic studies, based on a series of stoichiometric reactions with copper complexes, revealed that the key steps of this defluorosilylation reaction are 1) the 1,2-addition of a silylcopper intermediate to the polyfluoroalkene and 2) a subsequent selective ß-fluorine elimination, which generates a Cu-F species. The ß-fluorine elimination is facilitated by Lewis acidic F-Bpin, which is generated in situ during the defluorosilylation.

Copper-Catalyzed Regioselective Monodefluoroborylation of Polyfluoroalkenes en Route to Diverse Fluoroalkenes.

Monodefluoroborylation of polyfluoroalkenes has been achieved in a regioselective manner under mild conditions via copper catalysis. The method has shown an extremely broad scope of substrates, including (difluorovinyl)arenes, tetrafluoroethylene (TFE), (trifluorovinyl)arenes, and trifluoromethylated monofluoroalkenes. The choice of boron source was important for the efficient transformation of (difluorovinyl)arenes; (Bpin)2 was suitable for substrates with an electron-deficient aryl group and (Bnep)2 for those with an electron-rich aryl group. Derivatization of the (fluoroalkenyl)boronic acid esters to the corresponding potassium trifluoroborate salts has rendered the products easily isolable, which greatly improved the synthetic practicality of the monodefluoroborylation reaction. Stoichiometric experiments indicate that the fate of the regioselectivity depends on the mode of ß-fluorine elimination, which depends on the substrate. Further transformation of the boryl group has allowed facile preparation of fluoroalkene derivatives as exemplified by the synthesis of a fluoroalkene mimic of atorvastatin, which potently inhibited the enzyme activity of HMG-CoA reductase.

Pentacoordinated carboxylate π-allyl nickel complexes as key intermediates for the Ni-catalyzed direct amination of allylic alcohols.

Direct amination of allylic alcohols with primary and secondary amines catalyzed by a system made of [Ni(1,5-cyclooctadiene)2 ] and 1,1'-bis(diphenylphosphino)ferrocene was effectively enhanced by adding nBu4 NOAc and molecular sieves, affording the corresponding allyl amines in high yield with high monoallylation selectivity for primary amines and high regioselectivity for monosubstituted allylic alcohols. Such remarkable additive effects of nBu4 NOAc were elucidated by isolating and characterizing some nickel complexes, manifesting the key role of a charge neutral pentacoordinated η(3) -allyl acetate complex in the present system, in contrast to usual cationic tetracoordinated complexes earlier reported in allylic substitution reactions.

DPSK signal regeneration using a fiber-based amplitude regenerator.

An experiment of an all-optical DPSK-signal regeneration is reported. In the regenerator, incoming DPSK signals are first demodulated to on-off-keying signals, then amplitude-regenerated by a 2R regenerator, and subsequently used as control pulses for phase remodulation of clock pulses in an all-optical phase modulator. Penalty-free operation with reduced amplitude noise is demonstrated by the use of a two-stage fiberbased cascaded 2R amplitude regenerator in bidirectional configuration.

Differential expression of glutamate receptors in avian neural pathways for learned vocalization.

Learned vocalization, the substrate for human language, is a rare trait. It is found in three distantly related groups of birds-parrots, hummingbirds, and songbirds. These three groups contain cerebral vocal nuclei for learned vocalization not found in their more closely related vocal nonlearning relatives. Here, we cloned 21 receptor subunits/subtypes of all four glutamate receptor families (AMPA, kainate, NMDA, and metabotropic) and examined their expression in vocal nuclei of songbirds. We also examined expression of a subset of these receptors in vocal nuclei of hummingbirds and parrots, as well as in the brains of dove species as examples of close vocal nonlearning relatives. Among the 21 subunits/subtypes, 19 showed higher and/or lower prominent differential expression in songbird vocal nuclei relative to the surrounding brain subdivisions in which the vocal nuclei are located. This included relatively lower levels of all four AMPA subunits in lMAN, strikingly higher levels of the kainite subunit GluR5 in the robust nucleus of the arcopallium (RA), higher and lower levels respectively of the NMDA subunits NR2A and NR2B in most vocal nuclei and lower levels of the metabotropic group I subtypes (mGluR1 and -5) in most vocal nuclei and the group II subtype (mGluR2), showing a unique expression pattern of very low levels in RA and very high levels in HVC. The splice variants of AMPA subunits showed further differential expression in vocal nuclei. Some of the receptor subunits/subtypes also showed differential expression in hummingbird and parrot vocal nuclei. The magnitude of differential expression in vocal nuclei of all three vocal learners was unique compared with the smaller magnitude of differences found for nonvocal areas of vocal learners and vocal nonlearners. Our results suggest that evolution of vocal learning was accompanied by differential expression of a conserved gene family for synaptic transmission and plasticity in vocal nuclei. They also suggest that neural activity and signal transduction in vocal nuclei of vocal learners will be different relative to the surrounding brain areas.

Effect of social factors on the development of PKC expression in songbird brain.

Vocal learning by songbirds is affected by a song template and social factors. Normal male zebra finches with a song template and social interactions with other birds showed a transient increase of protein kinase C (PKC)-like immunoreactivity in the song control nuclei during a sensitive period of song learning. However, auditory isolation, which prevents the development of a song template induced an abnormal PKC development, which depended on the social interactions with other birds. In conclusion, social experience during an early sensitive period of song learning in the zebra finch is essential for the normal development of PKC expression in the robust nucleus of the arcopallium (RA), a premotor nucleus related to vocal plasticity.

Activation of protein kinase C by the error signal from a basal ganglia-forebrain circuit in the zebra finch song control nuclei.

An error signal from the anterior forebrain pathway (AFP) in the songbird brain is necessary for juvenile song learning and adult song maintenance. It induces the expression of protein kinase C (PKC) which is related to the plasticity in the robust nucleus of the archistriatum (RA), one of the song control nuclei in the forebrain. The glutamatergic inputs from the AFP activate mainly the NMDA receptors of the RA neurons. In order to clarify the molecular mechanism of error signal-induced PKC activation, two experiments were carried out. First, Ca2+ concentration was measured in a brain slice preparation from zebra finches using the fluorescent Ca2+ indicator Fura 2-AM. Glutamate increased the intracellular Ca2+ concentration ([Ca2+](i)) in RA neurons. This increase was inhibited by the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (AP5). Second, we examined the expression of PKC in the RA slice preparation after stimulation with glutamate for 10 min using PKCbeta1 fluorescence immunohistochemistry. Glutamate induced the activation of PKC as the translocation from the cytosol to the cell membrane, and the translocation was inhibited by AP5. These results indicate that the translocation of the PKC caused by the [Ca2+](i) elevation through NMDA receptors is concerned with the initial stage of error signal-induced plasticity in the RA.

Expression of protein kinase C in song control nuclei of deafened adult male Bengalese finches.

Auditory feedback is necessary to maintain singing in the adult male Bengalese finch (songbirds/oscines). Their song patterns are altered within a month following cochlear removal-induced deafness. Stabilization of song patterns occurs thereafter. To clarify what kind of changes appear in the brain of deafened birds, we examined immunohistochemically the expression of protein kinase C (PKC), considered a molecular marker for synaptic plasticity, in the robust nucleus of the archistriatum (RA), one of the song control nuclei in the forebrain of finches. Two weeks after cochlear removal, immunoreactive fibers and terminals in the RA transiently increased, and thereafter tended to decrease gradually. Moreover, the degree of song alteration and stability paralleled these changes in the RA. The immunoreactivity of the RA remained unchanged in intact birds. These results indicate that surgical deafening increases the expression of PKC in the RA. These changes in the RA are related to the alteration of song patterns in the deafened adult Bengalese finch.

Lesions of an avian forebrain nucleus prevent changes in protein kinase C levels associated with deafening-induced vocal plasticity in adult songbirds.

We investigated the participation of protein kinase C (PKC) in the regulation of vocal plasticity in songbirds. Deafening of adult Bengalese finches causes initial song alteration, followed by stabilization. In parallel, the expression of PKC beta1 increases transiently 2 weeks after deafening, and then decreases gradually in the robust nucleus of the arcopallium (RA) of Bengalese finches, similar to the pattern observed during developmental song learning. First, we showed that in adult zebra finches, whose songs change more gradually after auditory deprivation than those of Bengalese finches, PKC in RA also increased to an equal degree 2 weeks after deafening, despite the species difference. Second, double-labeling with an anterograde tracer and PKC immunofluorescence revealed that PKC immunoreactivity in RA was detected on the synaptic terminals from a high premotor vocal nucleus (HVC), but not from the lateral magnocellular nucleus of the anterior nidopallium (LMAN). To determine what causes deafening-induced PKC increases, we blocked signals from LMAN, the final output nucleus to RA in the anterior forebrain pathway (AFP), by a unilateral LMAN lesion prior to auditory deprivation of adult Bengalese finches. The PKC immunoreactivity increased in RA of the intact hemisphere; however, in RA on the lesioned side, it was less intense than that of the unlesioned side. Thus, the deafening-induced PKC expression was suppressed by lesioning of LMAN. These results suggest that an output signal from the AFP via LMAN induces the increase in PKC activity on HVC-RA synapses that may regulate song plasticity.

A molecular neuroethological approach for identifying and characterizing a cascade of behaviorally regulated genes.

Songbirds have one of the most accessible neural systems for the study of brain mechanisms of behavior. However, neuroethological studies in songbirds have been limited by the lack of high-throughput molecular resources and gene-manipulation tools. To overcome these limitations, we constructed 21 regular, normalized, and subtracted full-length cDNA libraries from brains of zebra finches in 57 developmental and behavioral conditions in an attempt to clone as much of the brain transcriptome as possible. From these libraries, approximately 14,000 transcripts were isolated, representing an estimated 4,738 genes. With the cDNAs, we created a hierarchically organized transcriptome database and a large-scale songbird brain cDNA microarray. We used the arrays to reveal a set of 33 genes that are regulated in forebrain vocal nuclei by singing behavior. These genes clustered into four anatomical and six temporal expression patterns. Their functions spanned a large range of cellular and molecular categories, from signal transduction, trafficking, and structural, to synaptically released molecules. With the full-length cDNAs and a lentiviral vector system, we were able to overexpress, in vocal nuclei, proteins of representative singing-regulated genes in the absence of singing. This publicly accessible resource http://songbirdtranscriptome.net can now be used to study molecular neuroethological mechanisms of behavior.