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Head-to-tail peptide macrocyclisations are significantly improved, as measured by isolated yields, reaction rates and product distribution, by substitution of one of the backbone amide C 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 O bonds with an oxetane ring., Cyclic peptides are an important source of new drugs but are challenging to produce synthetically. We show that head-to-tail peptide macrocyclisations are greatly improved, as measured by isolated yields, reaction rates and product distribution, by substitution of one of the backbone amide C 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 O bonds with an oxetane ring. The cyclisation precursors are easily made by standard solution- or solid-phase peptide synthesis techniques. Macrocyclisations across a range of challenging ring sizes (tetra-, penta- and hexapeptides) are enabled by incorporation of this turn-inducing element. Oxetane incorporation is shown to be superior to other established amino acid modifications such as N-methylation. The positional dependence of the modification on cyclisation efficiency is mapped using a cyclic peptide of sequence LAGAY. We provide the first direct experimental evidence that oxetane modification induces a turn in linear peptide backbones, through the observation of dNN (i, i + 2) and dαN (i, i + 2) NOEs, which offers an explanation for these improvements. For cyclic peptide, cLAGAY, a combination of NMR derived distance restraints and molecular dynamics simulations are used to show that this modification alters the backbone conformation in proximity to the oxetane, with the flexibility of the ring reduced and a new intramolecular H-bond established. Finally, we incorporated an oxetane into a cyclic pentapeptide inhibitor of Aminopeptidase N, a transmembrane metalloprotease overexpressed on the surface of cancer cells. The inhibitor, cCNGRC, displayed similar IC50 values in the presence or absence of an oxetane at the glycine residue, indicating that bioactivity is fully retained upon amide C 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 O bond replacement.

The first total synthesis of phyllostictine A is reported and evidence presented that the heterocyclic subunit is the key to the μM herbicidal activity., The first total synthesis of phyllostictine A (PA) is reported, which confirms the structure of this fungal metabolite and its (6S,7R,8S)-stereochemistry. Both synthetic PA and an analogue containing the 5-methylene-1,5-dihydro-2H-pyrrol-2-one nucleus exhibit μM inhibitory activity in root growth assays against Arabidopsis thaliana, indicating that this heterocyclic subunit is key to the herbicidal activity of the natural product.

To address the problem presented in this research, the purpose of this embedded mixed methods case study was to explore accounting students’ perceptions about the efficacy of using authentic assessment to determine how and to what extent experiential learning in the curriculum contributes to their preparation for certification and work in the accounting profession. The following central research question guided this investigational embedded case study: What are accounting students’ perceptions about the efficacy of using authentic assessment to determine how and to what extent experiential learning in the curriculum contributes to their preparation for certification and work in the accounting profession? To address this question and its accompanying sub-questions, the researcher followed a mixed methods, explanatory sequential data collection design, gathering data from accounting students and alumni by using a a survey and a focus group with selected participants, as well as artifacts from student participants’ classroom experiences in the Internal Revenue Service’s (IRS) Volunteer Income Tax Assistance (VITA) program., An analysis of the collected data led to numerous quantitative and explanatory qualitative findings. The data from the sources and data collection methods utilized were triangulated and coordinated to present results that ultimately addressed the central research question of the study. Further synthesis of the results led to the conclusion that experiential learning opportunities, especially when coupled with authentic assessment of such opportunities, are crucial to providing the learning and knowledge needed to prepare students for certification and work in the accounting profession. Furthermore, the results led to the conclusion that authentic assessment of the experiential learning project (ELP) known as the IRS VITA (Volunteer Income Tax Assistance) program does improve individual taxation knowledge, and especially confidence in that knowledge, but traditional classroom learning is still needed to prepare for certification and work in this area of the field. It was these final conclusions that led to implications and recommendations for practice and future research surrounding narrowing the perceived gap between accounting education and the workforce., Keywords: accounting, accounting certification, accounting curriculum, accounting education, authentic assessment, experiential learning, hands-on learning, problem-based learning, Volunteer Income Tax Assistance (VITA)

N-Arylitaconimides, accessible from maleic anhydride, anilines, and paraformaldehyde, react with arene diazonium salts in Pd-catalyzed Matsuda-Heck arylation to the pharmacologically relevant E-configured 3-arylmethylidene pyrrolidine-2,5-diones (also known as arylmethylidene succinimides) through exo-selective beta-H-elimination. The coupling proceeds at ambient temperature with the simple and easy-to-handle precatalyst Pd-II-acetate under ligandand base-free conditions. Notable features are high isolated yields, regio- and stereoselectivities, and short reaction times. In a comparative investigation, aryl iodides, bromides, and triflates were shown to be inferior coupling reagents in this reaction. The 3-arylmethylidene pyrrolidine-2,5-diones undergo second Matsuda-Heck coupling, which proceeds via endo-selective beta-H-elimination to give diarylmethyl-substituted maleimides as coupling products. These products can also be accessed in one flask by sequential addition of different arene diazonium salts to the starting itaconimide. The potential of 3-arylmethylidene succinimides as photoswitches was tested. Upon irradiation of the E-isomer at 300 nm, partial isomerization to the Z-isomer (E/Z = 65:35 in the photostationary state) was observed. The isomerization was found to be nearly completely reversible by irradiating the mixture at 400 nm.

2,5-Dicarboxy-2,5-dihydrofurans are key constituents of a number of natural products and have roles as intermediates in the formation of other such compounds of interest. Typically, these species are synthesized using toxic Pb(IV) salts. Electrochemical syntheses of 2,5-diacetoxy-2,5-dihydrofuran that do not require the use of lead have been reported, but a general lack of experimental detail has prevented these procedures from being more widely adopted. Moreover, no electrochemical study has yet reported the ratio of cis and trans isomers produced. Herein, we compare the chemical, lead-based route to 2,5-diacetoxy-2,5-dihydrofuran with a fully described electrosynthesis method. In doing so, we have discovered that the cis and trans isomers of this compound were previously incorrectly assigned in the literature, an error that we correct by obtaining the crystal structure of cis-2,5-diacetoxy-2,5-dihydrofuran. This allows the ratios of the isomers as prepared by the chemical (2 : 1 cis : trans) and electrochemical (7 : 5 cis : trans) methods to be obtained. Through experimental and computational insights, we propose a mechanism for the electrochemical synthesis of 2,5-dicarboxy-2,5-dihydrofurans and go some way towards validating this mechanism by synthesizing 2,5-dibutoxy-2,5-dihydrofuran electrochemically for the first time. We hope that these findings will provide some greater clarity to the literature surrounding the electrosynthesis and potential applications of 2,5-dicarboxy-2,5-dihydrofurans.