Kazuo Tachibana

Bio: Kazuo Tachibana is an academic researcher from University of Tokyo. The author has contributed to research in topics: Ring (chemistry) & Convergent synthesis. The author has an hindex of 40, co-authored 191 publications receiving 5617 citations. Previous affiliations of Kazuo Tachibana include National Institute of Advanced Industrial Science and Technology & Tohoku University.

Stereochemical Determination of Acyclic Structures Based on Carbon−Proton Spin-Coupling Constants. A Method of Configuration Analysis for Natural Products

Abstract: A method for elucidating the relative configuration of acyclic organic compounds was developed on the basis of carbon-proton spin-coupling constants ((2,3)J(C,H)) and interproton spin-coupling constants ((3)J(H,H)). This method is based on the theory that, in acyclic systems, the conformation of adjacent asymmetric centers is represented by staggered rotamers, and their relative stereochemistry can be determined using (2,3)J(C,H) and (3)J(H,H), because the combined use of these J values enables the identification of the predominant staggered rotamer(s) out of the six possible derived from threo and erythro configurations. Detailed conformational analysis for model compounds 1-4 revealed that this method is useful in most cases for assignment of the configuration of acyclic structures occurring in natural products, in which stereogenic methine carbons are often substituted with a methyl or a hydroxy (alkoxy) group. This J-based configuration analysis was applied to the stereochemical elucidation of carboxylic acid 5 derived from zooxanthellatoxin and proven to be a practical method even for natural products with complicated structures.

Absolute configuration of amphidinol 3, the first complete structure determination from amphidinol homologues: Application of a new configuration analysis based on carbon-hydrogen spin-coupling constants

Abstract: Dinoflagellates, a type of primitive unicellular algae, are a rich source of structurally and biologically intriguing natural products; e.g., okadaic acid, brevetoxins, ciguatoxins, and maitotoxin. Among these polyether-cyclic compounds, amphidinols are unique dinoflagellate metabolites since they are primarily made up of linear polyhydroxy structures. The first member of this group was isolated from the dinoflagellate Amphidinium klebsii as a potent antifungal substance by Yasumoto’s group.1a A series of homologues1b,c has since been found in the same genus, and Kobayashi’s group reported closely related compounds, luteophanols.2 These long-chain polyhydroxy compounds may be one of the most challenging targets for stereostructural elucidation since chiral centers are scattered over a flexible acyclic structure. Thus, little is known of the nature of the stereogenic centers in amphidinols. We recently developed J-based configuration analysis,3 which has been proven to be a powerful tool for the stereochemical determination of acyclic structures.3b In this method, 1,2-diastereomeric relationships between chiral centers are determined by choosing a correct staggered rotamer among six possibilities arising from erythro and threo configurations using spin-coupling constants (JH,H and JC,H, e.g., see Figure 1c for JC,H). In this paper, we report the complete configuration of amphidinol 3 (1), a representative homologue of the amphidinol family, mainly using this J-based method. From cellular extracts of A. klebsii obtained from 440 L of culture, 12 mg of 1 was isolated together with other amphidinol homologues.1b,c To facilitate measurements of JC,H, we prepared a 13C-enriched sample of 1 (25% 13C, 8 mg) by making another culture (200 L) in the presence of 12 mM NaHCO3. The stereochemical assignment of 1 was accomplished as follows; (a) the J-based method3 was used for acyclic parts with 1,2and 1,3-chiral centers, C20-C27, C32-C34, C38-C39, C44-C45, and C50-C51; (b) NOE analysis combined with J analysis was used for two ether cycles and their linkage C39C44; (c) the modified Mosher method4 and chromatographic/NMR comparison were used for degradation products to determine the absolute stereochemistry at C2, C6, C10, C14, C23, and C39. JH,H and JC,H values of intact 1 were measured by E.COSY5

Total Synthesis of Gambierol

Abstract: The first total synthesis of (-)-gambierol (1), a marine polycyclic ether toxin, has been achieved. Key features of the successful synthesis include (1) a convergent union of the ABC and EFGH ring fragments (5 and 6, respectively) via our developed B-alkyl Suzuki-Miyaura cross-coupling strategy leading to the octacyclic polyether core 4 and (2) a late-stage introduction of the sensitive triene side chain by use of Pd(PPh(3))(4)/CuCl/LiCl-promoted Stille coupling. The ABC ring fragment 5 was synthesized in a linear manner (B --> AB --> ABC), wherein the A ring was formed by intramolecular hetero-Michael reaction and the C ring was constructed via 6-endo cyclization of hydroxy epoxide 7. An improved synthetic entry to the EFGH ring fragment 6 is also described, in which SmI(2)-induced reductive cyclization methodology was applied to the stereoselective construction of the F and H rings, leading to 6 with remarkable overall efficiency. Stereoselective hydroboration of 5 and subsequent Suzuki-Miyaura coupling with 6 provided endocyclic enol ether 45 in high yield, which was then converted to octacyclic polyether core 4. Careful choice of the global deprotection stage was a key element for the successful total synthesis. Functionalization of the H ring and global desilylation gave (Z)-vinyl bromide 2. Finally, cross-coupling of 2 with (Z)-vinyl stannane 3 under Corey's Pd(PPh(3))(4)/CuCl/LiCl-promoted Stille conditions completed the total synthesis of (-)-gambierol (1).

Melittin-Like Peptides from the Shark-Repelling Defense Secretion of the Sole Pardachirus pavoninus.

Abstract: Three ichthyotoxic peptides, pardaxins P-I to P-3, have been isolated from the defense secretion of the sole Pardachirus pavoninus. Pavoninins, the steroid glycosides with shark-repelling ability, had previously been isolated therefrom. Each pardaxin consists of 33 amino acid residues having a distinctly hydrophilic carboxyl terminal region and a predominantly hydrophobic remainder; the pardaxin is thus strongly surfactant. These peptides show marked physical and pharmacological similarities to melittin, the major active constituent of bee venom, yet they lack sequence homology. They are probably also responsible for the predator-repelling property of the sole.

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

Abstract: The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.

Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality

Abstract: The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules.

Advances in molecular quantum chemistry contained in the Q-Chem 4 program package

Abstract: A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Moller–Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr_2 dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube.

Palladium-catalyzed cross-coupling reactions in total synthesis.

Abstract: In studying the evolution of organic chemistry and grasping its essence, one comes quickly to the conclusion that no other type of reaction plays as large a role in shaping this domain of science than carbon-carbon bond-forming reactions. The Grignard, Diels-Alder, and Wittig reactions are but three prominent examples of such processes, and are among those which have undeniably exercised decisive roles in the last century in the emergence of chemical synthesis as we know it today. In the last quarter of the 20th century, a new family of carbon-carbon bond-forming reactions based on transition-metal catalysts evolved as powerful tools in synthesis. Among them, the palladium-catalyzed cross-coupling reactions are the most prominent. In this Review, highlights of a number of selected syntheses are discussed. The examples chosen demonstrate the enormous power of these processes in the art of total synthesis and underscore their future potential in chemical synthesis.