Biosynthesis of Indole Diterpene Lolitrems: Radical-Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton

Lolitrems are tremorgenic indole diterpenes that exhibit a unique 5/6 bicyclic system of the indole moiety. Although genetic analysis has indicated that the prenyltransferase LtmE and the cytochrome P450 LtmJ are involved in the construction of this unique structure, the detailed mechanism remains to be elucidated. Herein, we report the reconstitution of the biosynthetic pathway for lolitrems employing a recently established genome-editing technique for the expression host Aspergillus oryzae. Heterologous expression and bioconversion of the various intermediates revealed that LtmJ catalyzes multistep oxidation to furnish the lolitrem core. We also isolated the key reaction intermediate with an epoxyalcohol moiety. This observation allowed us to establish the mechanism of radical-induced cyclization, which was firmly supported by density functional theory calculations and a model experiment with a synthetic analogue.     

Synthesis of C12-Keto Saxitoxin Derivatives with Unusual Inhibitory Activity Against Voltage-Gated Sodium Channels

A novel series of C12-keto-type saxitoxin (STX) derivatives bearing an unusual nonhydrated form of the ketone at C12 has been synthesized, and their Na_V-inhibitory activity has been evaluated in a cell-based assay as well as whole-cell patch-clamp recording. Among these compounds, 11-benzylidene STX ( 3 a ) showed potent inhibitory activity against neuroblastoma Neuro 2A in both cell-based and electrophysiological analyses, with EC₅₀ and IC₅₀ values of 8.5 and 30.7 nm , respectively. Interestingly, the compound showed potent inhibitory activity against tetrodotoxin-resistant subtype of Na_V1.5, with an IC₅₀ value of 94.1 nm . Derivatives 3 a – d and 3 f showed low recovery rates from Na_V1.2 subtype (ca 45–79 %) compared to natural dcSTX ( 2 ), strongly suggesting an irreversible mode of interaction. We propose an interaction model for the C12-keto derivatives with Na_V in which the enone moiety in the STX derivatives 3 works as Michael acceptor for the carboxylate of Asp¹⁷¹⁷.     

Supramolecular Sensor for Astringent Procyanidin C1: Fluorescent Artificial Tongue for Wine Components

An artificial tongue that detects astringent components for a comprehensive evaluation of taste has not been established to date. Herein, we first propose fluorescent polythiophene (PT) derivatives ( S1 – S3 ) modified with 3-pyridinium boronic acid as supramolecular chemosensors for wine components including astringent procyanidin C1. After numerous attempts for the synthetic conditions, more than 95 mol % of the PT unit was modified with the pyridinium boronic acid moiety. To evaluate the PT derivatives as chemosensors of the artificial tongue, qualitative and quantitative analyses were performed with four types of wine components (i.e., sweet, sour, bitter, and astringent tastes) in combination with pattern recognition models. Notably, procyanidin C1 in the actual wine sample was successfully detected in a quantitative manner. In other words, we have established an authentic artificial tongue using PT based supramolecular chemosensors.     

Synthesis of [1]benzothieno[3,2-b][1]benzothiophene (BTBT) and its higher homologs through palladium-catalyzed intramolecular decarboxylative arylation

We report herein an effective method for the construction of 4- and 7-ring benzo-fused thieno[3,2-b]thiophenes, involving palladium-catalyzed intramolecular decarboxylative arylation as the key step.     

Fine-patterning on glass substrates by the sol-gel method

A novel process has been developed to form fine patterns on glass substrates. The process consists of the following steps: (1) coating of gel film on a substrate, (2) patterning on the gel film, and (3) heat-treatment. The key point in this process is the control of hardening of the gel films by the addition of organic polymers such as polyethylene glycol (PEG). The addition of PEG increased the viscosity of the coating solutions and delayed the gelation time, but had little effect on the optical properties of the resultant heat-treated glass films. The newly developed process is expected to be applicable to the formation of the optical devices such as diffraction gratings and pre-groovesof optical memory disks.     

Electrical transport in n-type semiconducting Ge120BixSe70−xTe10 glasses

Resistivity and thermoelectric power were measured as a function of temperature and composition for Ge₂₀Bi_xSe_70?xTe₁₀ glasses (x = 0–11). The results were compared with the case of of Ge₂₀Bi_xSe_80?x glasses to see on the electrical properties the influence of the substitution of Te for a part of Se. The glasses show n-type conduction for x ? 9, which was not affected by the substitution of Te. The resistivity was about three orders of magnitude lower for the glasses with x < 10, and remained almost the same for x ? 10, compared with the glasses not containing Te. From the composition dependence of the calculated concentration of covalent bonds in the glasses, it was proposed that the appearance of n-type conduction was closely related to the formation of a sufficient number of BiSe bonds and the disappearance of the bonds between two chalcogen atoms such as TeSe or SeSe bonds, and that the remarkably low resistivity in the present glasses with x < 10 was likely to be attributed to the formation of TeSe bonds.     

Spontaneous formation of super water-repellent fractal surfaces in mixed wax systems

Alkylketene dimers (AKDs) and triglyceride waxes form fractal surfaces spontaneously and show super water-repellent property. Spontaneous formation of fractal structures on their surfaces takes place when the meta-stable crystalline phase of the waxes transforms to the thermodynamically stable form of crystal. The triglyceride waxes form the meta-stable alpha-phase in whole specimen when solidified from their melt. In the case of AKD, on the other hand, only a small portion of the specimen solidifies in the meta-stable form of crystal. The surface of the AKD, however, becomes fractal in the whole part. We have, thus, examined the fractal structure formation in the mixed wax systems in which one wax forms fractal surfaces and the other one does not. In the stearic acid/tristearin mixed system as a typical one, the super water-repellent fractal surfaces form in the higher composition region of tristearin than that of the eutectic point in their mixture.     

Total Biosynthesis of Melleolides from Basidiomycota Fungi: Mechanistic Analysis of the Multifunctional GMC Oxidase Mld7

Mushroom terpenoids are biologically and chemically diverse fungal metabolites. Among them, melleolides are representative sesquiterpenoids with a characteristic protoilludane skeleton. In this study, we applied a recently established hot spot knock-in method to elucidate the biosynthetic pathway leading to 1α-hydroxymelleolide. The biosynthesis of the sesquiterpene core involves the cytochrome P450 catalyzing stepwise hydroxylation of the Δ⁶-protoilludene framework and a stereochemical inversion process at the C5 position catalyzed by short-chain dehydrogenase/reductase family proteins. The highlight of the biosynthesis is that the flavoprotein Mld7 catalyzes an oxidation-triggered double-bond shift accompanying dehydration and acyl-group-assisted substitution with two different nucleophiles at the C6 position to afford the Δ⁷-protoilludene derivatives, such as melleolide and armillarivin. The complex reaction mechanism was proposed by DFT calculations. Of particular importance is that product distribution is regulated by interaction with the cell membrane.     

Theoretical study on second hyperpolarizabilities of singlet diradical square planar nickel complexes involving o-semiquinonato type ligands

Hybrid density functional theory method is applied for investigating the diradical character dependence of the second hyperpolarizability (gamma) of square planar nickel complexes involving several types of bidentate ligands [o-C6H4XY, where X = Y = O, NH, S, Se, and PH as well as (X, Y) = (NH, NH2) and (S, NH2)]. It is found that, as a function of the donor atoms, the diradical character of these complexes varies from 0.0 to 0.884 and is associated with substantial variations of gamma ranging from 14 x 10(3) to 819 x 10(3) au. In particular, the largest gamma values are associated with intermediate diradical characters in good agreement with the structure-property relationship obtained for pure hydrocarbon systems. Increasing the electronegativity of the X and Y donor groups of the ligands leads to larger diradical characters as a result of the enhancement of the double bond nature of the C=X(Y) bonds, which further stabilizes the diradicals on both-end benzene rings. This demonstrates that the electronegativities of the donor atoms of the ligands become a tuning parameter of the diradical character and then of the gamma values of these complexes.     

Preparation of hollow poly(divinyl benzene) particles with multiple holes in the shell by microsuspension polymerization with the SaPSeP method

Hollow polymer particles with multiple holes in the shell were prepared by aqueous microsuspension polymerization of micrometer-sized, monodisperse divinylbenzene/n-hexadecane droplets in the presence of sodium dodecyl sulfate (SDS) at concentrations above 4 mM utilizing the Self-assembling Phase-Separated Polymer (SaPSeP) method developed by the authors. The total surface area of the holes per particle increased with an increase in the SDS concentration. At [SDS] = 10 mM, “flower-like” non-spherical particles were formed. Part CCCXV of series “Studies on Suspension and Emulsion”