Total Synthesis of Decahydroquinoline Poison Frog Alkaloids ent-cis-195A and cis-211A

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama

Total Synthesis of Decahydroquinoline Poison Frog Alkaloids ent-\u3ci\u3ecis\u3c/i\u3e-195A and \u3ci\u3ecis\u3c/i\u3e-211A

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama

Biological Effects of Narrow Band Pulsed Electric Fields

This paper describes the process of narrow band pulsed electric fields (NPEFs) and its effect on mammalian cells. The NPEF consists of a pulse modulated sinusoidal wave (PMSW), which allows delivery of well-defined electric fields in terms of frequency, field strength and deposition energy to the biological systems. 100 μs long sinusoidal electric fields with a frequency of 0.02, 2 or 50 MHz and field strengths of up to 2 kV/cm are applied to CHO cells with variation in the DNA density in the cells investigated by means of Acridine Orange assay. The experiments indicate that 50 MHz fields cause DNA degradation without cell membrane defects, while 0.02 MHz fields lead to an increase in membrane permeability which is similar to the effect known as electroporation. The intermediate frequency of 2 MHz influences both the membrane and DNA. It is demonstrated that the MHz range narrowband electric fields with the amplitude level of 1 kV/cm cause intracellular effects in mammalian cells

Tissue-Restricted Expression of Nrf2 and Its Target Genes in Zebrafish with Gene-Specific Variations in the Induction Profiles

The Keap1-Nrf2 system serves as a defense mechanism against oxidative stress and electrophilic toxicants by inducing more than one hundred cytoprotective proteins, including antioxidants and phase 2 detoxifying enzymes. Since induction profiles of Nrf2 target genes have been studied exclusively in cultured cells, and not in animal models, their tissue-specificity has not been well characterized. In this paper, we examined and compared the tissue-specific expression of several Nrf2 target genes in zebrafish larvae by whole-mount in situ hybridization (WISH). Seven zebrafish genes (gstp1, mgst3b, prdx1, frrs1c, fthl, gclc and hmox1a) suitable for WISH analysis were selected from candidates for Nrf2 targets identified by microarray analysis. Tissue-restricted induction was observed in the nose, gill, and/or liver for all seven genes in response to Nrf2-activating compounds, diethylmaleate (DEM) and sulforaphane. The Nrf2 gene itself was dominantly expressed in these three tissues, implying that tissue-restricted induction of Nrf2 target genes is defined by tissue-specific expression of Nrf2. Interestingly, the induction of frrs1c and gclc in liver and nose, respectively, was quite low and that of hmox1a was restricted in the liver. These results indicate the existence of gene-specific variations in the tissue specificity, which can be controlled by factors other than Nrf2