In many macroorganisms, the ultimate source of potent biologically active natural products has remained elusive due to an inability to identify and culture the producing symbiotic microorganisms. As a model system for developing a meta-omic approach to identify and characterize natural product pathways from invertebrate-derived microbial consortia we chose to investigate the ET-743 (Yondelis®) biosynthetic pathway. This molecule is an approved anti-cancer agent obtained in low abundance (10−4–10−5% w/w) from the tunicate Ecteinascidia turbinata, and is generated in suitable quantities for clinical use by a lengthy semi-synthetic process. Based on structural similarities to three bacterial secondary metabolites, we hypothesized that ET-743 is the product of a marine bacterial symbiont. Using metagenomic sequencing of total DNA from the tunicate/microbial consortium we targeted and assembled a 35 kb contig containing 25 genes that comprise the core of the NRPS biosynthetic pathway for this valuable anti-cancer agent. Rigorous sequence analysis based on codon usage of two large unlinked contigs suggests that Candidatus Endoecteinascidia frumentensis produces the ET-743 metabolite. Subsequent metaproteomic analysis confirmed expression of three key biosynthetic proteins. Moreover, the predicted activity of an enzyme for assembly of the tetrahydroisoquinoline core of ET-743 was verified in vitro. This work provides a foundation for direct production of the drug and new analogs through metabolic engineering. We expect that the interdisciplinary approach described is applicable to diverse host-symbiont systems that generate valuable natural products for drug discovery and development.

Inverted teaching, not to be confused with hybrid learning, is a relatively new pedagogy in which lecture is shifted outside of class and traditional homework is done in class. Though some inverted teaching (IT) designs have been published in different fields, peer-reviewed reports in university chemistry remain quite rare. To that end, herein is disclosed a sophomore organic chemistry course design in which two groups of students were each taught by one of two methods: Group 1 through traditional lecture (TL) and Group 2 through IT. Design rationale and objectives are discussed. Academic performances are compared, along with anonymous student feedback contrasting the two techniques (TL vs IT). Student attendance and viewership, instructor prep time, and total lecture time are also presented for both styles.

In synchronously-delivered, multisite classrooms, the physical separation between distance students and instructors may create a perceived divide that negatively affects learning. Building on prior experience in flipping organic chemistry in single-site face-to-face (F2F) classes, we decided to extend our approach to multisite, synchronously delivered general chemistry courses. Our thought was to narrow the perceived instructor–student divide in distance teaching by using the flexible in-class time that flipping affords to increase the number of positive teacher/distance-student interactions. In this effort, we gradually developed a technique called “bridging questions,” through which the instructor becomes more familiar with student interests and then connects those interests to chemistry topics discussed in class. Despite anticipating overall positive results, actual consequences were mixed: after flipping the class, evaluation scores and positive feedback increased slightly. However, the mean final exam scores decreased for F2F students by 26.2% but increased for distance students by 4.4% (not statistically significant). Thus, this new approach (flipping with bridging questions) may have unintentionally skewed our focus to distance students, though this conclusion is speculative. (We acknowledge statistical limitations, due to small sample sizes.) We accordingly advocate proactive efforts to balance engagement between both F2F and distance sites. In this paper we also discuss modifications we made to adapt our flipped format to multisite, synchronously delivered freshman chemistry courses, as well as the basic idea of bridging questions in general.

We recently shared our design of a two-semester flipped organic chemistry course, in which we gave students in-class quizzes to incentivize attendance and watching the lecture videos in advance. With a second iteration, we planned to make the video-watching experience more engaging. We accordingly hypothesized that if students completed short at-home quizzes while watching the videos, then attentiveness, engagement, and learning would increase. We tested this with a later section of the course, dividing the material into 13 units. For units 1-6, we gave in-class quizzes; for 7-13, quizzes were at home. Although units 1-6 and 7-13 covered different material, we were nonetheless surprised when students' average quiz scores decreased for the take-home quizzes, because they did not have a time limit and were open-book, unlike the inclass quizzes. Anonymous survey feedback showed a strong preference for quizzes in class and indications that take-home quizzes demotivated attendance and pre-class watching of the videos. Thus, for analogous flipped-course designs in chemistry, we recommend an in-class quizzing strategy over take-home quizzes to positively affect engagement, learning, and attendance. Of note, this course was synchronously-delivered to two groups of students at geographically-distinct satellite locations.

2-Acylimidazoles are alkylated under phase-transfer conditions with cinchonidinium catalysts at -40 degrees C with allyl and benzyl electrophiles in high yield with excellent enantioselectivity (79 to >99% ee). The acylimidazole substrates are made in three steps from bromoacetic acid via the N-acylmorpholine adduct. The catalyst is made in high purity allowing for S-product formation (6-20 h) under mild conditions, consistent with an ion-pair mechanism. The products are readily converted to useful ester products using methyltriflate and sodium methoxide, via a dimethylacylimidazolium intermediate without racemization. The process is efficient, direct, and amenable to other electrophiles and transformations that proceed through an enolate intermediate.