Approach to the Core Structure of Signermycin B.

Among the natural tetramic acids with a decalinoyl part, signermycin B is unique because it contains a cis-decalin. In this paper, we demonstrate that the cis-decalin section of signermycin B can be accessed by an anionic oxy-Cope rearrangement. The substrate, a tricyclic dienol was prepared by an intramolecular Diels-Alder reaction of a masked ortho-benzoquinone, generated by oxidation of an α-methoxyphenol in presence of cis-2-hexenol. After a superfluous bromine on the cycloadduct was removed, reaction of the tricyclic ketone with isopropenylmagnesium bromide led to the tricyclic trienol that underwent the oxy-Cope rearrangement to a cis-decalinone. While we could show, that introduction of the 4-ethyl substituent (signermycin B numbering) is possible by enolate alkylation, the 4-epi-isomer was formed.

Error-related cardiac deceleration: Functional interplay between error-related brain activity and autonomic nervous system in performance monitoring.

Coordinated interactions between the central and autonomic nervous systems are crucial for survival due to the inherent propensity for human behavior to make errors. In our ever-changing environment, when individuals make mistakes, these errors can have life-threatening consequences. In response to errors, specific reactions occur in both brain activity and heart rate to detect and correct errors. Specifically, there are two brain-related indicators of error detection and awareness known as error-related negativity and error positivity. Conversely, error-related cardiac deceleration denotes a momentary slowing of heart rate following an error, signaling an autonomic response. However, what is the connection between the brain and the heart during error processing? In this review, we discuss the functional and neuroanatomical connections between the brain and heart markers of error processing, exploring the experimental conditions in which they covary. Given the current limitations of available data, future research will continue to investigate the neurobiological factors governing the brain-heart interaction, aiming to utilize them as combined markers for assessing cognitive control in healthy and pathological conditions.

Effects of the number of competing responses on neural signatures of pre- and post-response conflict.

The optimization of human performance requires the continuous monitoring of behavioral conflicts. According to conflict monitoring theory, the dorsal anterior cingulate cortex registers response conflict which is reflected by two electrophysiological signatures, the N2 and the Ne/ERN. The theory assumes that, if a stimulus activates an incorrect response that competes with the correct response, pre-response conflict on correct trials (reflected by the N2) is enhanced but post-response conflict on error trials (reflected by the Ne/ERN) is reduced. Here, we asked whether response conflict depends on the number of competing incorrect responses activated by a stimulus, that is, whether the N2 is further enhanced and the Ne/ERN is further reduced if two incorrect responses are activated as compared to one. To this end, we used a modified flanker paradigm, in which the two flankers were associated either with the same incorrect response or with different incorrect responses. Our results indicate an increased N2 on correct trials and a reduced Ne/ERN on error trials in the latter as compared to the former condition. These results confirm central predictions of conflict monitoring theory and demonstrate that response conflict is directly related to the number of competing incorrect responses.

The role of action inhibition for behavioral control in joint action.

When two individuals share a task with a common goal, coordinating one's own and the other's actions is pivotal. Inhibition of one's own actions when it is the other's turn to act is assumed to play a crucial role in this process. For instance, in the joint Simon task, two individuals share a two-choice task such that one of them responds to one stimulus type and ignores the stimulus type to which the other responds. Because stimuli can either appear on one's own or on the other's side, stimulus location can conflict with stimulus identity, thus slowing response time. It has previously been shown that such conflict leads to a reduction of the detrimental effects of conflict on immediately upcoming trials both following own responses and even more so following the other's responses. This amplified trial-to-trial adjustment following the other's responses has been assumed to reflect the inhibition of own responses on the other's trials. The present study tested this hypothesis by comparing sequential trial-to-trial adjustments following correct responses and commission errors on which the inhibition of own responses has failed. As expected, adjustments were stronger following the other's correct responses than following own correct responses. Crucially, such amplification of sequential adjustment was not observed following own commission errors on the other's trials. This shows that amplification of sequential adjustments following the other's trials depend on successful inhibition of own responses on these trials and points to a crucial role of response inhibition for behavioral control in joint action.

Early correlates of error-related brain activity predict subjective timing of error awareness.

Humans are remarkably reliable in detecting errors in their behavior. Whereas error awareness has been assumed to emerge not until 200-400 ms after an error, the so-called early error sensations refer to the subjective feeling of having detected an error even before the erroneous response was executed. Here, we collected electroencephalogram (EEG) to track how early error sensations are reflected in neural correlates of performance monitoring. Participants first had to perform a task, and then had to indicate whether an error has occurred and whether this error was detected before or after response execution. EEG results showed that early error sensations were associated with an earlier peak of the error-related negativity (Ne/ERN), a component of error-related brain activity that occurs briefly after the error response. This demonstrates that early error-related activity influences metacognitive judgments on the time course of error awareness, and thus contributes to error awareness.

Formal Total Synthesis of Salvinorin A.

The generation of the quaternary stereocenter at the C9 position of salvinorin A precursors by the Claisen rearrangement was investigated. The required allyl alcohol was prepared from a Wieland-Miescher ketone using a known γ-hydroxylation, reduction of the enone double bond, cyanohydrin formation, and elimination, yielding an unsaturated nitrile. A two-step reduction led to the required allyl alcohol. The subsequent Johnson-Claisen rearrangement provided a mixture of two diastereomeric 1,4-unsaturated esters in a ratio of around 2.6 : 1. The major isomer could be converted to a key intermediate of the Hagiwara synthesis of salvinorin A.

LC-HRMS screening of per- and polyfluorinated alkyl substances (PFAS) in impregnated paper samples and contaminated soils.

High per- and polyfluorinated alkyl substance (PFAS) concentrations have been detected in agricultural soils in Southwest Germany. Discharges of PFAS-contaminated paper sludge and compost are suspected to be the cause of the contamination. Perfluorinated carboxylic acids (PFCAs) have been detected also in groundwater, drinking water, and plants in this area. Recently, previously unknown compounds have been identified by high-resolution mass spectrometry (HRMS). Major contaminants were polyfluorinated dialkylated phosphate esters (diPAPs) and N-ethyl perfluorooctane sulfonamide ethanol-based phosphate diester (diSAmPAP). In this study, HRMS screening for PFAS was applied to 14 soil samples from the contaminated area and 14 impregnated paper samples which were from a similar period than the contamination. The paper samples were characterized by diPAPs (from 4:2/6:2 to 12:2/12:2), fluorotelomer mercapto alkyl phosphates (FTMAPs; 6:2/6:2 to 10:2/10:2), and diSAmPAP. In soil samples, diPAPs and their transformation products (TPs) were the major contaminants, but also FTMAPs, diSAmPAP, and their TPs occurred. The distribution patterns of the carbon chain lengths of the precursor PFAS in soil samples were shown to resemble those in paper samples. This supports the hypothesis that paper sludge is a major source of contamination. The presence of major degradation products like PFCAs, FTSAs, or PFOS and their distribution of carbon chain lengths indicate the activity of biotic or abiotic degradation processes and selective leaching processes from the upper soil horizons.

Total Synthesis of the Plant Growth Promoter Auxofuran Featuring a Gold(I) Catalyzed Furan Formation.

A concise synthesis of auxofuran (1) was developed. Starting with a Sonogashira cross-coupling reaction, enynol (10) was prepared. A gold(I) catalyzed cycloisomerization led to disubstituted furan 12. Via an intramolecular Friedel-Crafts cyclization, a dihydrobenzofuranone was obtained. Functional group manipulations, including benzylic oxidation, led to the target molecule.

Cognitive modelling reveals distinct electrophysiological markers of decision confidence and error monitoring.

Is confidence in perceptual decisions generated by the same brain processes as decision itself, or does confidence require metacognitive processes following up on the decision? In a masked orientation task with varying stimulus-onset-asynchrony, we used EEG and cognitive modelling to trace the timing of the neural correlates of confidence. Confidence reported by human observers increased with stimulus-onset-asynchrony in correct and to a lesser degree in incorrect trials, a pattern incompatible with established models of confidence. Electrophysiological activity was associated with confidence in two different time periods, namely 350-500 â€‹ms after stimulus onset and 250-350 â€‹ms after the response. Cognitive modelling revealed that only the activity following on the stimulus exhibited the same statistical regularities as confidence, while the statistical pattern of the activity following the response was incompatible with confidence. It is argued that electrophysiological markers of confidence and error awareness are at least in parts distinct.

Are errors detected before they occur? Early error sensations revealed by metacognitive judgments on the timing of error awareness.

Errors in choice tasks are not only detected fast and reliably, participants often report that they knew that an error occurred already before a response was produced. These early error sensations stand in contrast with evidence suggesting that the earliest neural correlates of error awareness emerge around 300 ms after erroneous responses. The present study aimed to investigate whether anecdotal evidence for early error sensations can be corroborated in a controlled study in which participants provide metacognitive judgments on the subjective timing of error awareness. In Experiment 1, participants had to report whether they became aware of their errors before or after the response. In Experiment 2, wemeasured confidence in these metacognitive judgments. Our data show that participants report early error sensations with high confidence in the majority of error trials across paradigms and experiments. These results provide first evidence for early error sensations, informing theories of error awareness.

Error-related pupil dilation is sensitive to the evaluation of different error types.

Adjusting behavior following errors is essential for successful goal-directed performance. Error-related pupil dilation indicates increased autonomic arousal and has been shown to predict adaptive adjustments of post-error behavior. Because different types of errors may require different behavioral adjustments, we investigated whether this process is also sensitive to the evaluation of different types of errors. We used a four-choice flanker task where errors occur either by pressing a button associated with the distractors (flanker errors), or by pressing a button not associated with the stimulus at all (nonflanker errors). Flanker errors imply suboptimal selective attention to the target and are therefore of increased significance for successful performance. Pupil dilation was larger for flanker errors than nonflanker errors, and only pupil dilation on flanker errors predicted a decrease of error probability on the next trial. Moreover, the error-related negativity, an electrophysiological marker of early error monitoring in the medial frontal cortex, was larger on flanker errors anticipating the effect of error type on pupil dilation. These results show that error-related pupil dilation is sensitive to the type and significance of errors and correlates with adaptive behavioral adjustments accordingly. This suggests that mechanisms underlying error-related pupil dilation receive inputs from error evaluation mechanisms in the medial frontal cortex.

Synthesis of allyl alcohol as a method to valorise glycerol from the biodiesel production.

Reaction of triglycerides with trimethyl orthoformate in presence of camphorsulfonic acid (CSA) gave the fatty acid methyl esters (FAMEs, 4) in good yield. However, under these conditions, the protected glycerol could not be obtained. Formation of orthoesters 9 was possible in a separate reaction using very weak acidic conditions, namely catalytic amounts of pyridinium para-toluenesulfonate (PPTS). Subjecting the orthoesters 9 to thermolysis at 270 °C gave allyl alcohol (11) with good efficiency.

Total Synthesis of Biselyngbyolide B and Its C21-C22 Z-Isomer.

Investigations toward the synthesis of the 18-membered macrolactone biselyngbyolide B (2) from a C1-C13 and a C14-C23 fragment are described. As a key reaction in the synthesis of the C1-C13 fragment, we used an asymmetric propargylation of chiral vinylketene silyl N, O-acetal 12. Access to a C14-C23 fragment featuring a skipped diene and a sensitive allyl alcohol function was initially attempted via reductive fragmentation of a pyran template. However, this ring opening on iodide 32 with t-BuLi led to dienynol 33 with a 21 Z double bond. With a silyl protecting group at 3-OH and by implementing an intramolecular Stille coupling for macrolactonization, the 21 Z-isomer of biselyngbyolide B (47) was obtained. For preparation of a C14-C23 fragment with the 21 E-configuration, a cross-coupling of vinylstannane 48 with 4-bromocrotonate (49) set the configuration of the two double bonds. Biselyngbyolide B (2) was then accessed by an intramolecular Heck coupling. In preliminary biological cytotoxicity assays, 2 turned out to be active, whereas the 21 Z-isomer 47 was much less active. The 3-OMEM analogue 40 was devoid of activity. These results support the notion that the side chain with the correct configuration is relevant for binding to the Ca2+-ATPase and the biological activity.

Errors can elicit an error positivity in the absence of an error negativity: Evidence for independent systems of human error monitoring.

Errors in human behavior elicit a cascade of brain activity related to performance monitoring and error detection. Whereas the early error-related negativity (Ne/ERN) has been assumed to reflect a fast mismatch or prediction error signal in the medial frontal cortex, the later error positivity (Pe) is viewed as a correlate of conscious error processing. A still open question is whether these components represent two independent systems of error monitoring that rely on different types of information to detect an error. Here, we investigated the prediction that the Ne/ERN but not the Pe requires a representation of the correct response to emerge. To this end, we created a condition in which no information about the correct response was available while error detection was still possible. We hypothesized that a Pe, but no Ne/ERN should be obtained in this case. Participants had to classify targets but ignore flankers that were always associated with an incorrect response. Targets but not flankers were masked with varying target-masking intervals. Crucially, on some trials no target at all was presented, thus preventing the representation of a correct response and the emergence of an Ne/ERN. However, because flankers were easily visible and responses to the flankers were always incorrect, detection of these flanker errors was still possible. In line with predictions of a multiple-systems account, we observed a robust Pe in the absence of an Ne/ERN for these errors. Moreover, this Pe relied on the same neural activity as that on trials with a visible target, as revealed by multivariate pattern analysis. These findings demonstrate that the mechanisms reflected by the two components use different types of information to detect errors, providing evidence for independent systems of human error monitoring.

Rhodomyrtone (Rom) is a membrane-active compound.

Particularly in Asia medicinal plants with antimicrobial activity are used for therapeutic purpose. One such plant-derived antibiotic is rhodomyrtone (Rom) isolated from Rhodomyrtus tomentosa leaves. Rom shows high antibacterial activity against a wide range of Gram-positive bacteria, however, its mode of action is still unclear. Reporter gene assays and proteomic profiling experiments in Bacillus subtilis indicate that Rom does not address classical antibiotic targets like translation, transcription or DNA replication, but acts at the cytoplasmic membrane. In Staphylococcus aureus, Rom decreases the membrane potential within seconds and at low doses, causes release of ATP and even the excretion of cytoplasmic proteins (ECP), but does not induce pore-formation as for example nisin. Lipid staining revealed that Rom induces local membrane damage. Rom's antimicrobial activity can be antagonized in the presence of a very narrow spectrum of saturated fatty acids (C15:0, C16:0, or C18:0) that most likely contribute to counteract the membrane damage. Gram-negative bacteria are resistant to Rom, presumably due to reduced penetration through the outer membrane and its neutralization by LPS. Rom is cytotoxic for many eukaryotic cells and studies with human erythrocytes showed that Rom induces eryptosis accompanied by erythrocyte shrinkage, cell membrane blebbing, and membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Rom's distinctive interaction with the cytoplasmic membrane reminds on the amphipathic, alpha-helical peptides, the phenol-soluble modulins (PSMs), and renders Rom an important tool for the investigation of membrane physiology.

Intramolecular Diels-Alder Reactions of Tethered Enoate Substituted Furans Induced by Dialkylaluminum Chloride.

Gold(I)-catalyzed cycloisomerization of enynols 11 and 17, obtained by Sonogashira coupling, led to the tethered enoate-substituted furans 14 and 19. While attempts at thermal and several Lewis acid induced intramolecular Diels-Alder reactions remained fruitless, dialkylaluminum chloride led to the formation of hexahydroindene and octahydronaphthalene derivatives 20-23. Their formation can be explained by Lewis acid induced opening of the epoxy bridge with transfer of one alkyl group to the intermediate cycloadduct.

Neural correlates of reconfiguration failure reveal the time course of task-set reconfiguration.

The ability to actively prepare for new tasks is crucial for achieving goal-directed behavior. The task-switching paradigm is frequently used to investigate this task-set reconfiguration. In the present study, we adopted a novel approach to identify a neural signature of reconfiguration in event-related potentials. Our method was to isolate neural correlates of reconfiguration failure and to use these correlates to reveal the time course of reconfiguration in task switches and task repetitions. We employed a task-switching paradigm in which two types of errors could be distinguished: task errors (the incorrect task was applied) and response errors (an incorrect response for the correct task was provided). Because differential activity between both error types distinguishes successful and failed reconfiguration, this activity could be used as a neural signature of the reconfiguration process. We found that, whereas reconfiguration takes place on task repetitions and task switches, it occurred earlier in the former than in the latter. Single-trial analysis revealed that the same activity predicted the amplitude of error-related brain activity, providing further support that this preparatory activity reflects reconfiguration. Our results implicate that reconfiguration is not switch-specific but that task switches and task repetitions differ with respect to the time course of reconfiguration. Furthermore, this study demonstrates that considering neural correlates of failure is a promising approach to link cognitive mechanisms to specific neural processes.

A Radical-Based Synthesis of Lingzhiol.

The polycyclic natural product lingzhiol [(±)-1] was synthesized from dimethoxytetralone 8 via cyclization of an intermediate benzylic radical, generated from spiroepoxide 14, onto an alkynyl substituent generating tetracyclic compound 13 with an exocyclic double bond. After oxidative cleavage of the double bond of 13 and reduction of the keto function of 23, the correct diastereomer, 12-syn, was converted to lingzhiol (1) via known steps. In a similar manner, lingzhiol analogue 39 was synthesized from 5-methoxy-1-tetralone (27).

Working memory load impairs the evaluation of behavioral errors in the medial frontal cortex.

Early error monitoring in the medial frontal cortex enables error detection and the evaluation of error significance, which helps prioritize adaptive control. This ability has been assumed to be independent from central capacity, a limited pool of resources assumed to be involved in cognitive control. The present study investigated whether error evaluation depends on central capacity by measuring the error-related negativity (Ne/ERN) in a flanker paradigm while working memory load was varied on two levels. We used a four-choice flanker paradigm in which participants had to classify targets while ignoring flankers. Errors could be due to responding either to the flankers (flanker errors) or to none of the stimulus elements (nonflanker errors). With low load, the Ne/ERN was larger for flanker errors than for nonflanker errors-an effect that has previously been interpreted as reflecting differential significance of these error types. With high load, no such effect of error type on the Ne/ERN was observable. Our findings suggest that working memory load does not impair the generation of an Ne/ERN per se but rather impairs the evaluation of error significance. They demonstrate that error monitoring is composed of capacity-dependent and capacity-independent mechanisms.

Neural signatures of adaptive post-error adjustments in visual search.

Errors in speeded choice tasks can lead to post-error adjustments both on the behavioral and on the neural level. There is an ongoing debate whether such adjustments result from adaptive processes that serve to optimize performance or whether they reflect interference from error monitoring or attentional orientation. The present study aimed at identifying adaptive adjustments in a two-stage visual search task, in which participants had to select and subsequently identify a target stimulus presented to the left or right visual hemifield. Target selection and identification can be measured by two distinct event-related potentials, the N2pc and the SPCN. Using a decoder analysis based on multivariate pattern analysis, we were able to isolate the processing stages related to error sources and post-error adjustments. Whereas errors were linked to deviations in the N2pc and the SPCN, only for the N2pc we identified a post-error adjustment, which exhibits key features of source-specific adaptivity. While errors were associated with an increased N2pc, post-error adjustments consisted in an N2pc decrease. We interpret this as an adaptive adjustment of target selection to prevent errors due to disproportionate processing of the task-irrelevant target location. Our study thus provides evidence for adaptive post-error adjustments in visual search.