Synthesis of 5‐ and 8‐Deoxytetrodotoxin

Tetrodotoxin, a toxic principle of puffer fish intoxication, is one of the most famous marine natural products owing to its complex structure and potent biological activity, which leads to fatal poisoning. Continuous synthetic studies on tetrodotoxin and its analogues to elucidate biologically interesting issues associated with tetrodotoxin have led to the development of versatile routes for a variety of tetrodotoxin derivatives. With the aim of investigating the structure–activity relationship of tetrodotoxin with voltage‐gated sodium channels, this study describes the first total syntheses of 5‐deoxytetrodotoxin, a natural analogue of tetrodotoxin, and 8‐deoxytetrodotoxin, an unnatural analogue, from a newly designed, versatile intermediate in an efficient manner. An estimation of the biological activities of these compounds reveals the importance of the hydroxy groups at the C‐5 and C‐8 positions on the inhibition of voltage‐gated sodium channels.     

Determining an Effective UV Radiation Exposure Time for Vitamin D Synthesis in the Skin Without Risk to Health: Simplified Estimations from UV Observations

UV radiation contains erythemally weighted UV, as well as UV that synthesizes vitamin D₃. Here, we attempted to determine the relationship between these factors by numerical simulation of atmospheric parameters, such as total ozone, using a simplified “SMART2” model for radiative transfer. Both forms of UV were almost linearly correlated with each other for a comparably large UV radiation exposure, larger than UV Index ~1.6. If erythemally weighted UV, which carries a risk of sunburn, is known, the amount of UV exposure needed for vitamin D synthesis in the epidermis can be estimated using this relationship. The production of 10 μg (400 IU) of vitamin D per day takes approximately 1/3 of the time needed to reach the minimal erythemal dose (MED) for an effective skin area of 600 cm² for skin phototype III. For an area of 1200 cm², 1/6 of that exposure time suffices. From a UV Index that is commonly used, the risks and benefits can be evaluated using this linear relationship, which will enable people to effectively manage their UV exposure and consider the risks and benefits to optimize health outcomes.     

Efficient stereoselective synthesis of gamma-N-glycosyl asparagines by N-glycosylation of primary amide groups

The efficient and elegant synthesis of N-glycosides by N-glycosylation of asparagine-containing peptides is described. Glycosylation of primary amides with glycosyl N-phenyltrifluoroimidates in the presence of a catalytic amount of TMSOTf in nitromethane smoothly proceeded to provide the corresponding N-glycosyl amino acids in excellent yields. This coupling method was adaptable to the coupling of various glycosyl donors with amino acids and peptides.     

Material coefficients of multiphase thermoporoelasticity for anisotropic micro-heterogeneous porous media

Constitutive equations of thermoporoelasticity for two-phase fluid system derived by Coussy (2007) are extended to those for multiphase system with anisotropic micro-heterogeneous porous media. All the material coefficients are found to be expressed by coefficients common to saturated thermoporoelasticity and saturation-dependent effective stress coefficients. Experimental conditions to evaluate thermal pore expansivity and saturation dependent effective stress coefficients are also presented. Material coefficients for orthotropy and transverse isotropy, which are often seen in actual porous media, are explicitly listed to facilitate application.     

THEORETICAL STUDY OF PENTAVALENT HALOSILICONATES: STRUCTURE AND CHARGE DELOCALIZATION

Journal of Structural Chemistry - This study is performed to detect the pentavalent silicon center in the structure of pentavalent-halosiliconate R–O–Si(CH3)3X– and...     

Stereocontrolled Total Synthesis of Polygalolide A

The total synthesis of polygalolide A, a secondary metabolite that was isolated from a Chinese medicinal plant, is reported. A key issue in this synthesis was construction of an oxabicyclo[3.2.1] skeleton, which was solved by the development of an intramolecular Ferrier‐type C‐glycosylation of a glucal with siloxyfuran as an internal nucleophile. The substrate was prepared from D ‐glucal by the introduction of trimethylsilylacetylene and siloxyfuran groups. Although C‐glycosylation did not occur under the conditions found from model experiments, further examination revealed that the combination of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and 2,4,6‐collidine successfully afforded the desired product as a single diastereomer. The siloxy group at the C3 position played a crucial role in the stereocontrol of this reaction. The product was further transformed into a tetracyclic compound as follows: The vinyl ether and acetylenic moieties were reduced and the siloxy group was removed with a Barton–McCombie reaction. The construction of the six‐membered ether and the γ‐lactone provided the tetracyclic compound. Finally, a phenolic moiety was introduced by using a Mukaiyama aldol reaction to furnish polygalolide A.     

Total Synthesis of Chiriquitoxin,an Analogue of Tetrodotoxin Isolated from the Skin of a Dart Frog

The first total synthesis of chiriquitoxin, the most structurally complex analogue of tetrodotoxin isolated from a Costa Rican dart frog, has been accomplished from a newly designed intermediate for a variety of tetrodotoxin derivatives. The synthesis includes the third total synthesis of tetrodotoxin in this laboratory, and its intermediate was transformed into chiriquitoxin by a stereocontrolled aldol reaction with a D ‐camphor‐derived lactone for installation of the unique side chain, and a new deprotection of methylthiomethyl (MTM) ether by using a Pummerer rearrangement.     

Atomic simulations to evaluate effects of stacking fault energy on interactions between edge dislocation and spherical void in face-centred cubic metals

In this study, molecular dynamics simulations were performed to elucidate the effects of stacking fault energy (SFE) on the physical interactions between an edge dislocation and a spherical void in the crystal structure of face-centred cubic metals at various temperatures and for different void sizes. Four different types of interaction morphologies were observed, in which (1) two partial dislocations detached from the void separately, and the maximum stress corresponded to the detachment of the trailing partial; (2) two partial dislocations detached from the void separately, and the maximum stress corresponded to the detachment of the leading partial; (3) the partial dislocations detached from the void almost simultaneously without jog formation; and (4) the partial dislocations detached from the void almost simultaneously with jog formation. With an increase in void size or SFE, the interaction morphology changed in the above-mentioned order. It was observed that the magnitude of the critical resolved shear stress (CRSS) and its dependence on the SFE were determined by these interaction morphologies. The value of the CRSS in the case of interaction morphology (1) is almost equal to an analytical one based on the linear elasticity by employing the Burgers vector of a single partial dislocation. The maximum value of the CRSS is also obtained by the analytical model with the Burgers vector of the two partial dislocations.