Stereoselective synthesis of macrocyclic peptides via a dual olefin metathesis and ethenolysis approach

Macrocyclic compounds occupy an important chemical space between small molecules and biologics and are prevalent in many natural products and pharmaceuticals. The growing interest in macrocycles has been fueled, in part, by the design of novel synthetic methods to these compounds. One appealing strategy is ring-closing metathesis (RCM) that seeks to construct macrocycles from acyclic diene precursors using defined transition-metal alkylidene catalysts. Despite its broad utility, RCM generally gives rise to a mixture of E- and Z-olefin isomers that can hinder efforts for the large-scale production and isolation of such complex molecules. To address this issue, we aimed to develop methods that can selectively enrich macrocycles in E- or Z-olefin isomers using an RCM/ethenolysis strategy. The utility of this methodology was demonstrated in the stereoselective formation of macrocyclic peptides, a class of compounds that have gained prominence as therapeutics in drug discovery. Herein, we report an assessment of various factors that promote catalyst-directed RCM and ethenolysis on a variety of peptide substrates by varying the olefin type, peptide sequence, and placement of the olefin in macrocycle formation. These methods allow for control over olefin geometry in peptides, facilitating their isolation and characterization. The studies outlined in this report seek to expand the scope of stereoselective olefin metathesis in general RCM

Ruthenium-catalysed Z-selective cross metathesis of allylic-substituted olefins

The Z-selective cross metathesis of allylic-substituted olefins is explored with recently developed ruthenium-based metathesis catalysts. The reaction proceeds with excellent stereoselectivity for the Z-isomer (typically >95%) and yields of up to 88% for a variety of allylic substituents. This includes the first synthesis of Z-α,β-unsaturated acetals by cross metathesis and their elaboration to Z-α,β-unsaturated aldehydes. In addition, the reaction is tolerant of a variety of cross partners, varying in functionality and steric profile

A Western Range Extension for Caprella scaura (Amphipoda: Caprellidae) in the Aransas Bay Ecosystem, Texas

During March 2009, the skeleton shrimp Caprella scaura and Paracaprella tenuis (Amphipoda: Caprellidae) were collected from several locations throughout the Aransas Bay, Texas ecosystem from Texas Parks and Wildlife fishery—independent trawl and oyster dredge samples. This is a western range expansion for C. scaura; P. tenuis has been reported from this area before. Both species were exclusively associated with a bryozoan, Bugula neritina. Densities of both species ranged between 0.1–3.4 individuals per gram of attached bryozoans. A reproductive population is likely established since several sizes, including adult males and gravid females, were observed. No caprellids were observed after early April, which coincided with a reduction in bryozoan occurrence in our routine monthly samples. These collections represent the first documented occurrence of C. scaura west of Florida

Culture Wars and COVID-19 Conduct: Christian Nationalism, Religiosity, and Americans’ Behavior During the Coronavirus Pandemic

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.During the COVID‐19 pandemic, Americans’ behavioral responses were quickly politicized. Those on the left stressed precautionary behaviors, while those on the (religious) right were more likely to disregard recommended precautions. We propose the far right response was driven less by partisanship or religiosity per se, but rather by an ideology that connects disregard for scientific expertise; a conception of Americans as God's chosen and protected people; distrust for news media; and allegiance to Trump―Christian nationalism. Analyzing panel data collected in the thick of the COVID‐19 crisis, we find Christian nationalism was the leading predictor that Americans engaged in incautious behavior like eating in restaurants, visiting family/friends, or gathering with 10+ persons (though not attending church), and was the second strongest predictor that Americans took fewer precautions like wearing a mask or sanitizing/washing one's hands. Religiosity, in contrast, was the leading predictor that Americans engaged in more frequent precautionary behaviors. Findings document that Christian nationalism, not religious commitment per se, undergirded the far‐right response to COVID‐19 that disregarded precautionary recommendations, thus potentially worsening the pandemic.Data collection was supported via a research grant awarded by the Charles Koch Foundation to Joshua B. Grubbs and by the Jack Shand Research Grant from the Society for the Scientific Study of Religion awarded to Samuel L. Perry. Neither granting agency played any role whatsoever in designing the survey instrument or analyzing the results

Z-Selective Olefin Metathesis on Peptides: Investigation of Side-Chain Influence, Preorganization, and Guidelines in Substrate Selection

Olefin metathesis has emerged as a promising strategy for modulating the stability and activity of biologically relevant compounds; however, the ability to control olefin geometry in the product remains a challenge. Recent advances in the design of cyclometalated ruthenium catalysts has led to new strategies for achieving such control with high fidelity and Z selectivity, but the scope and limitations of these catalysts on substrates bearing multiple functionalities, including peptides, remained unexplored. Herein, we report an assessment of various factors that contribute to both productive and nonproductive Z-selective metathesis on peptides. The influence of sterics, side-chain identity, and preorganization through peptide secondary structure are explored by homodimerization, cross metathesis, and ring-closing metathesis. Our results indicate that the amino acid side chain and identity of the olefin profoundly influence the activity of cyclometalated ruthenium catalysts in Z-selective metathesis. The criteria set forth for achieving high conversion and Z selectivity are highlighted by cross metathesis and ring-closing metathesis on diverse peptide substrates. The principles outlined in this report are important not only for expanding the scope of Z-selective olefin metathesis to peptides but also for applying stereoselective olefin metathesis in general synthetic endeavors

About Eggs--Eggs in the Diet.

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Self-reported Addiction to Pornography in a Nationally Representative Sample: The Roles of Use Habits, Religiousness, and Moral Incongruence

BACKGROUND AND AIMS: Despite controversies regarding its existence as a legitimate mental health condition, self-reports of pornography addiction seem to occur regularly. In the United States, prior works using various sampling techniques, such as undergraduate samples and online convenience samples, have consistently demonstrated that some pornography users report feeling dysregulated or out of control in their use. Even so, there has been very little work in US nationally representative samples to examine self-reported pornography addiction. METHODS: This study sought to examine self-reported pornography addiction in a US nationally representative sample of adult Internet users (N = 2,075). RESULTS: The results indicated that most participants had viewed pornography within their lifetimes (n = 1,461), with just over half reporting some use in the past year (n = 1,056). Moreover, roughly 11% of men and 3% of women reported some agreement with the statement I am addicted to pornography. Across all participants, such feelings were most strongly associated with male gender, younger age, greater religiousness, greater moral incongruence regarding pornography use, and greater use of pornography. DISCUSSION AND CONCLUSION: Collectively, these findings are consistent with prior works that have noted that self-reported pornography addiction is a complex phenomenon that is predicted by both objective behavior and subjective moral evaluations of that behavior