Efficient syntheses of eight key cannabinoids were established and optimized. Predominant cannabinoids such as cannabigerol (CBG-C 5 ) and cannabidiol (CBD-C 5 ) were prepared from olivetol via regioselective condensation. Further treatments of CBD led to Δ 9tetrahydrocannabinol (THC-C 5 ), Δ 8 -iso-tetrahydrocannabinol (iso-THC-C 5 ), and cannabinol (CBN-C 5 ). Alternatively, a [3 + 3] annulation between olivetol and citral yielded the minor cannabinoid cannabichromene (CBC-C 5 ), which was converted into two very rare polycycles, cannabicyclol (CBL-C 5 ) and cannabicitran (CBT-C 5 ), in a one-pot reaction. Finally, all eight syntheses were extended by utilizing resorcinol and two phenolic analogues, achieving a cannabinoid group with more than 30 compounds through a facile synthesis strategy.

Glaucoma is a blinding eye disease that affects about 70 million patients globally today. The cannabinoid receptors and the endocannabinoid system have found attention for new drug concepts. This review will analyze the potential of cannabinoids, primarily tetrahydrocannabinol, THCVS, and cannabinol, as drug candidates and the role of CB1/CB2 receptors with regard to the pathophysiology of glaucoma. The mode of action of cannabinoids as innovative drug candidates and recent formulations for topical delivery will be discussed. Cannabinoid receptors with associated TRPV channels will be evaluated for their potential as drug targets. Especially the role of the endocannabinoid system (fatty acid amide hydrolase, monoacylglycerol lipase) impacting the prostaglandin network (cyclooxygenase, PGE, PGF) and neuroprotection by inhibition of nitric oxide radical formation is in the focus of this review. Delivery systems, including recent clinical trials, will be analyzed to evaluate the potential for innovative future ophthalmological drugs.

Background: Assembly algorithm choice should be a deliberate, well-justified decision when researchers create genome assemblies for eukaryotic organisms from third-generation sequencing technologies. While third-generation sequencing by Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio) have overcome the disadvantages of short read lengths specific to next-generation sequencing (NGS), third-generation sequencers are known to produce more error-prone reads, thereby generating a new set of challenges for assembly algorithms and pipelines. Since the introduction of third-generation sequencing technologies, many tools have been developed that aim to take advantage of the longer reads, and researchers need to choose the correct assembler for their projects. Results: We benchmarked state-of-the-art long-read de novo assemblers, to help readers make a balanced choice for the assembly of eukaryotes. To this end, we used 13 real and 72 simulated datasets from different eukaryotic genomes, with different read length distributions, imitating PacBio CLR, PacBio HiFi, and ONT sequencing to evaluate the assemblers. We include five commonly used long read assemblers in our benchmark: Canu, Flye, Miniasm, Raven and Redbean. Evaluation categories address the following metrics: reference-based metrics, assembly statistics, misassembly count, BUSCO completeness, runtime, and RAM usage. Additionally, we investigated the effect of increased read length on the quality of the assemblies, and report that read length can, but does not always, positively impact assembly quality. Conclusions: Our benchmark concludes that there is no assembler that performs the best in all the evaluation categories. However, our results shows that overall Flye is the best-performing assembler, both on real and simulated data. Next, the benchmarking using longer reads shows that the increased read length improves assembly quality, but the extent to which that can be achieved depends on the size and complexity of the reference genome.

An efficient synthesis of 2,5-dihydrobenzoxepine analogues was developed without using protecting groups. Regioselective allylation was optimized through a recent method utilizing magnesium dicarboxylates. Grubbs catalysts were applied to investigate ring-closing metathesis. The scope of the present route was extended to produce four analogues, which provided novel cannabinoid-like 2,5-dihydrobenzoxepines in sufficient quantities to permit in vitro assays on recombinant CB1/CB2 receptors. In vitro assays related to CB1/CB2 receptors did not indicate any activity.