Bioinspired Syntheses of Seven Macrodiolide Analogs of Aplysiatoxin by the Late-Stage Functionalization of a Dehydroaplysiatoxin Derivative.

Aplysiatoxin (ATX) is a bioactive polyketide natural product produced by cyanobacteria and characterized by macrodiolide and spiroacetal moieties. Many structurally diverse analogs of ATX have been reported but are little studied due to the minuscule quantities in which they have been isolated. We hypothesized that most of these analogs are biosynthesized from anhydroATX, a dehydrated form of ATX, and report a synthesis of the phenolic OMe ether of anhydro-deBr-ATX, as well as syntheses of seven macrodiolide ATX analogs, OTX-B1, B2, M, J, and neo-deBr-ATX-A, G, and J, according to the biosynthetic hypothesis.

A practical, biomimetic, one-pot synthesis of firefly luciferin.

The bioluminescence reaction of firefly luciferase with D-luciferin has become an indispensable imaging technique in modern biology and life science experiments, but the high cost of D-luciferin is limiting its further application. Here, we report a practical, one-pot synthesis of D-luciferin from p-benzoquinone (p-BQ), L-cysteine methyl ester and D-cysteine, with an overall yield of 46%. Our route, which is six steps in length and proceeds via 2-cyano-6-hydroxybenzothiazole, is inspired by the mechanistic study of our previously reported biomimetic, non-enzymatic, one-pot formation of L-luciferin from p-BQ and L-cysteine.

Isolation of Paraphaeoketones: A Plausible Biosynthetic Explanation for Paraphaeolactones via a Benzilic Acid Rearrangement Rather than a Favorskii Rearrangement.

Paraphaeoketones A-C (-) were isolated from the culture broth of sp. KT4192. Their structures and relative configurations were determined using spectroscopic analysis and verified through density functional theory (DFT)-based chemical shift calculations.

5, 6, 11-trideoxy tetrodotoxin attracts tiger puffer Takifugu rubripes.

Tetrodotoxin (TTX) is a potent neurotoxin that binds to voltage-gated sodium channels and blocks the passage of sodium ions. TTX is widely distributed in both terrestrial and marine organisms, and the toxic puffers are believed to accumulate TTX through the food chain. Although pufferfish was previously thought to be attracted by TTX, recent finding from electroolfactogram (EOG) studies have indicated that the olfactory epithelium of T.

Total Synthesis of 19-Nordigitoxigenin, An Antiaroside Y Aglycon.

The first total synthesis of 19-nordigitoxigenin, an aglycon of antiroside Y, has been achieved. The key steps of our synthesis are (i) construction of the 19-norsteroid ring system via a Mizoroki-Heck reaction between a bromoanisole corresponding to the A-ring and cyclic alkene incorporating the CD-rings, followed by a Friedel-Crafts-type cyclodehydration, and (ii) incorporation of the butenolide moiety at C17 via a silyl-tethered radical cyclization and subsequent ozone oxidation.

Assessing the safety and suitability of using silver vine as an olfactory enrichment for cats.

Olfactory enrichment is a strategy that can improve welfare among animals managed in captivity, such as household domestic cats. Catnip () and silver vine () that produce iridoids are used as olfactory enrichments for cats, but little is known about the safety or the best plant resources to use that maximize positive cat responses. We report physiological effects and suitable harvest and drying methods for using silver vine as olfactory enrichment.

Geographical differences in the composition of tetrodotoxin and 5,6,11-trideoxytetrodotoxin in Japanese pufferfishes and their origins.

Tetrodotoxin (TTX)-bearing fish are thought to accumulate TTXs in their bodies through a food chain that begins with marine bacteria. However, the mechanism of TTXs transfer between prey and predators in the food chain remains unclear and the reasons for regional differences in pufferfish toxicity are also unknown. To investigate these matters, we collected juveniles of four species of pufferfish, Takifugu alboplumbeus, Takifugu flavipterus, Takifugu stictonotus, and Chelonodon patoca, from various locations in the Japanese Islands, and subjected them to liquid chromatography-tandem mass spectrometry analysis for TTX and its analog 5,6,11-trideoxyTTX (TDT).

The Asymmetric Total Synthesis and Configuration Confirmation of Aplysiaenal and Nhatrangin A, Truncated Derivatives of Aplysiatoxin and Oscillatoxin.

Asymmetric total syntheses of aplysiaenal () and nhatrangin A (), truncated derivatives of the aplysiatoxin/oscillatoxin family of marine natural products, from configurationally defined intermediates are described. NMR spectra of our synthesized nhatrangin A did not match with either those obtained from authentic samples of the natural product or material obtained via two other total syntheses, but were similar to that obtained from a sample obtained in a third total synthesis. By independently synthesizing the fragments used in its total syntheses, we were able to confirm the configuration of nhatrangin A and clarified that the discrepancy in the spectroscopic data is due to salt formation of the carboxylic acid moiety.

[Epithelioid Hemangioendothelioma of the Upper Mediastinum:Report of a Case].

A 81-year-old woman was referred to our hospital for neck discomfort. Chest computed tomography (CT) showed a tumor in the upper mediastinum. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed the mild accumulation in the tumor.

Changes in Tissue Distribution of Tetrodotoxin and Its Analogues in Association with Maturation in the Toxic Flatworm, Planocera multitentaculata.

The toxic flatworm, Planocera multitentaculata, possesses highly concentrated tetrodotoxin (TTX), also known as pufferfish toxin, throughout its life cycle, including the egg and larval stages. Additionally, TTX analogues, 5,6,11-trideoxyTTX and 11-norTTX-6(S)-ol, have also been detected in the flatworm. The high concentration of TTX in the eggs and larvae appears to be for protection against predation, and 11-norTTX-6(S)-ol in the pharyngeal tissue in the adults is likely used to sedate or kill prey during predation.

[Primary Pericardial Malignant Mesothelioma:Report of a Case].

A 67-year-old woman was referred to our hospital for cough and fever. Chest computed tomography (CT) showed some masses showing slightly enhanced effect in the pericardium. FDG-PET showed the accumulation of FDG in the masses.

An almost nontoxic tetrodotoxin analog, 5,6,11-trideoxytetrodotoxin, as an odorant for the grass puffer.

Toxic puffers contain the potent neurotoxin, tetrodotoxin (TTX). Although TTX is considered to serve as a defense substance, previous behavioral studies have demonstrated that TTX acts as an attractive pheromone for some toxic puffers. To elucidate the physiological mechanism of putative pheromonal action of TTX, we examined whether grass puffers Takifugu alboplumbeus can detect TTX.

Structural verification of petromyzestrosterol by total syntheses of both C14-epimers of its 3--methyl derivative.

The structure of petromyzestrosterol, a pheromonal steroid of the sea lamprey, was verified by total syntheses of both C14-epimers of its 3--methyl derivative. The key features of our synthesis involve (1) a highly stereoselective Mizoroki-Heck reaction to unite the A- and CD-ring segments and (2) Friedel-Crafts-type cyclodehydration to construct the B-ring. Petromyzestrosterol is concluded to bear an α-configured C14 hydroxy group based on a comparison of NMR data of both the synthesized C14-epimers of the 3--methyl derivative with those of the natural petromyzestrosterol.

Domestic cat damage to plant leaves containing iridoids enhances chemical repellency to pests.

Catnip () and silver vine () produce iridoids with arthropod-repellent effects. Cats rub and roll against these plants, transferring iridoids to their fur that repels mosquitoes. Cats also lick and chew plant leaves during this response, although the benefit of this additional behavior has remained unknown.

Tetrodotoxins in the flatworm Planocera multitentaculata.

The marine polyclad flatworm Planocera multitentaculata is known to possess high levels of tetrodotoxin (TTX), but the presence of TTX analogues in the species has been unexplored. In this study, TTX and several analogues such as 5,6,11-trideoxyTTX, monodeoxyTTXs, dideoxyTTXs, and 11-norTTX-6(S)-ol were identified in three adults and egg plates of P. multitentaculata using high resolution liquid chromatography-mass spectrometry (HR-LC/MS) for the first time.

Total Syntheses of the Proposed Biosynthetic Intermediates of Tetrodotoxin Tb-210B, Tb-226, Tb-242C, and Tb-258.

The collective synthesis of the four -cyclic guanidines Tb-210B, Tb-226, Tb-242C, and Tb-258, all of which have been isolated from puffer fish and are considered possible biosynthetic intermediates of tetrodotoxin, has been achieved. Our synthesis is based on the stepwise deoxygenation or hydroxylation of a common intermediate, prepared from a known oxazoline.

Green spotted puffers detect a nontoxic TTX analog odor using crypt olfactory sensory neurons.

Toxic puffers accumulate their defense substance (tetrodotoxin; TTX) through the food chain. Although the previous study suggests that 5,6,11-trideoxyTTX, a nontoxic TTX analog detected simultaneously with TTX in toxic puffers or their prey, acts as an olfactory chemoattractant for grass puffers, it is unclear whether toxic puffers are commonly attracted to 5,6,11-trideoxyTTX, and which types of olfactory sensory neurons (OSNs) detect 5,6,11-trideoxyTTX. Here, we demonstrated that green spotted puffer, a phylogenetically distant species from the grass puffer, is attracted to 5,6,11-trideoxyTTX.

Local Differences in the Toxin Amount and Composition of Tetrodotoxin and Related Compounds in Pufferfish () and Toxic Goby () Juveniles.

Tetrodotoxin (TTX)-bearing fish ingest TTX from their preys through the food chain and accumulate TTX in their bodies. Although a wide variety of TTX-bearing organisms have been reported, the missing link in the TTX supply chain has not been elucidated completely. Here, we investigated the composition of TTX and 5,6,11-trideoxyTTX in juveniles of the pufferfish, , and toxic goby, , using LC-MS/MS, to resolve the missing link in the TTX supply chain.

Synthesis of the 8-Deoxy Analogue of 4,9-Anhydro-10-hemiketal-5-deoxy-tetrodotoxin, a Proposed Biosynthetic Precursor of Tetrodotoxin.

Despite decades of research, the biosynthesis of tetrodotoxin, also known as a puffer fish toxin, remains an unsolved mystery. We disclose a synthesis of the 8-deoxy analogue of 4,9-anhydro-10-hemiketal-5-deoxy-tetrodotoxin, a possible biosynthetic precursor of tetrodotoxin isolated from the Japanese toxic newt, by an intramolecular radical cyclization of a known starting material.

Total synthesis and biological evaluation of oscillatoxins D, E, and F.

Oscillatoxins (OTXs) and aplysiatoxins are biosynthetically related polyketides produced by marine cyanobacteria. We previously developed a synthetic route to phenolic O-methyl analogs of OTX-D and 30-methyl-OTX-D during collective synthesis of these natural products. According to our synthetic strategy, we achieved total synthesis of OTX-D, 30-methyl-OTX-D, OTX-E, and OTX-F by deprotecting the O-methyl group in an earlier intermediate, and determined their biological activities.

Total Synthesis of the Cardiotonic Steroid (+)-Cannogenol.

The total synthesis of (+)-cannogenol, an aglycon common to various biologically important cardiotonic glycosides, has been achieved. Synthesis of the versatile intermediate involves Mizoroki-Heck and intramolecular Diels-Alder reactions from the enantiomerically pure CD-ring segment, newly prepared in a multidecagram scale this time. Total synthesis by the site-selective transformations of the versatile intermediate demonstrated the applicability of our synthetic approach.

The characteristic response of domestic cats to plant iridoids allows them to gain chemical defense against mosquitoes.

Domestic cats and other felids rub their faces and heads against catnip () and silver vine () and roll on the ground as a characteristic response. While this response is well known, its biological function and underlying mechanism remain undetermined. Here, we uncover the neurophysiological mechanism and functional outcome of this feline response.