Epoxide ring-opening reactions for abundant production of mugineic acids and nicotianamine probes.

A succinct synthetic approach to mugineic acids and 2'-hydroxynicotianamine was established. Unlike all other synthetic methods, this approach utilized epoxide ring-opening reactions to form two C-N bonds and is characterized by the absence of redox reactions. Mugineic acid was synthesized from three readily available fragments on a gram scale in 6 steps. The protected 2'-hydroxynicotianamine was also synthesized in 4 steps, and the dansyl group, serving as a fluorophore, was introduced through a click reaction after propargylation of the 2'-hydroxy group. The dansyl-labeled nicotianamine (NA) iron complexes were internalized by oocytes overexpressing ZmYS1 (from maize) or PAT1 (from human) transporters, indicating successful transport of the synthesized NA-probe through these transporters.


Development of 1,3a,6a-triazapentalene derivatives as practical erasable fluorescent cell staining reagents.


Inactivation of siderophore iron-chelating moieties by the fungal wheat root symbiont Pyrenophore biseptata

We investigated the ability of four plant and soil-associated fungi to modify or degrade siderophore structures leading to reduced siderophore iron-affinity in iron-limited and iron-replete cultures. Pyrenophora biseptata, a melanized fungus from wheat roots, was effective in inactivating siderophore iron-chelating moieties. In the supernatant solution, the tris-hydroxamate siderophore desferrioxamine B (DFOB) underwent a stepwise reduction of the three hydroxamate groups in DFOB to amides leading to a progressive loss in iron affinity. A mechanism is suggested based on the formation of transient ferrous iron followed by reduction of the siderophore hydroxamate groups during fungal high-affinity reductive iron uptake. P. biseptata also produced its own tris-hydroxamate siderophores (neocoprogen I and II, coprogen and dimerum acid) in iron-limited media and we observed loss of hydroxamate chelating groups during incubation in a manner analogous to DFOB. A redox-based reaction was also involved with the tris-catecholate siderophore protochelin in which oxidation of the catechol groups to quinones was observed. The new siderophore inactivating activity of the wheat symbiont P. biseptata is potentially widespread among fungi with implications for the availability of iron to plants and the surrounding microbiome in siderophore-rich environments.


A Simple and Powerful tert-Butylation of Carboxylic Acids and Alcohols


A suitable stereoisomer of vibrioferrin probes for iron uptake of Vibrio parahaemolyticus


1,3a,6a-Triazapentalene derivatives as photo-induced cytotoxic small fluorescent dyes

1,3a,6a-Triazapentalene (TAP) is a compact fluorescent chromophore whose fluorescence properties vary greatly depending on the substituents on the TAP ring. This study investigated the photo-induced cytotoxicities of various TAP derivatives. Among the derivatives, 2-p-nitrophenyl-TAP showed significant cytotoxicity to HeLa cells under UV irradiation but no cytotoxicity without UV. In addition, the photo-induced cytotoxicity of 2-p-nitirophenyl-TAP was found to be cancer cell selective and effective against HeLa cells and HCT 116 cells. Under UV irradiation, 2-p-nitrophenyl-TAP generated reactive oxygen species (ROS) that induced an apoptosis and ferroptosis in cancer cells. Therefore, it was revealed that 2-p-nitrophenyl-TAP is the most compact dye that can generate ROS by photoirradiation.


Uptake mechanism of iron-phytosiderophore from the soil based on the structure of yellow stripe transporter

Calcareous soils cover one-third of all land and cause severe growth defects in plants due to the poor water solubility of iron at high pH. Poaceae species use a unique chelation strategy, whereby plants secrete a high-affinity metal chelator, known as phytosiderophores (mugineic acids), and reabsorb the iron-phytosiderophore complex by the yellow stripe 1/yellow stripe 1-like (YS1/YSL) transporter for efficient uptake of iron from the soil. Here, we present three cryo-electron microscopy structures of barley YS1 (HvYS1) in the apo state, in complex with an iron-phytosiderophore complex, Fe(III)-deoxymugineic acid (Fe(III)-DMA), and in complex with the iron-bound synthetic DMA analog (Fe(III)-PDMA). The structures reveal a homodimeric assembly mediated through an anti-parallel β-sheet interaction with cholesterol hemisuccinate. Each protomer adopts an outward open conformation, and Fe(III)-DMA is bound near the extracellular space in the central cavity. Fe(III)-PDMA occupies the same binding site as Fe(III)-DMA, demonstrating that PDMA can function as a potent fertilizer in an essentially identical manner to DMA. Our results provide a structural framework for iron-phytosiderophore recognition and transport by YS1/YSL transporters, which will enable the rational design of new, high-potency fertilizers.


Total synthesis of proposed structures of 4,10-dihydroxy 8,12-guaianolides

The first total syntheses of two 4,10-dihydroxy-8,12-guaianolides that were reported to be natural products were achieved. Toward the syntheses of a collection of related guaianolides, the typical 5,7-fused system of 8,12-guaianolides was constructed by a ring expansion reaction of a hydroxylated coronafacic acid analogue that can be practically synthesized and optically resolved. The total syntheses of these compounds revealed that the previously reported structures of both natural products were incorrect.


A heterogeneous bifunctional silica-supported Ag2O/Im+Cl- catalyst for efficient CO2 conversion


Efficient construction of the hexacyclic ring core of palau'amine: the pKa concept for proceeding with unfavorable equilibrium reactions


Development of a novel antioxidant based on a dimeric dihydroisocoumarin derivative


Iron uptake mediated by the plant-derived chelator nicotianamine in the small intestine

Iron is an essential metal for all living organisms that is absorbed in the intestinal cells as a heme-chelated or free form. It is unclear how important plant-derived chelators, such as nicotianamine (NA), an organic small molecule that is ubiquitous in crops, vegetables, and various other foods, contribute to iron bioavailability in mammals. We performed electrophysiological assays with Xenopus laevis oocytes and radioactive tracer experiments with Caco-2 cells. The findings revealed that the proton-coupled amino acid transporter SLC36A1 (PAT1) transports iron in the form of NA-Fe (II) complex in vitro. Decreased expression of hPAT1 by RNA interference in Caco-2 cells reduced the uptake of NA-Fe (II) complex. The uptake of inorganic Fe (II) was relatively unaffected. These results imply that PAT1 transports iron as a NA-Fe (II) complex. The rate of Fe absorption in the spleen, liver, and kidney was higher when mice were orally administered NA-Fe (II) compared with free Fe (II). The profile of site-specific PAT1 expression in the mouse intestine coincided with those of NA and iron contents, which were the highest in the proximal jejunum. Orally administered NA-Fe (II) complex in mice was detected in the proximal jejunum by thin layer chromatography. In contrast, much less Fe (or NA) was detected in the duodenum, where the divalent metal transporter SLC11A2 (DMT1) absorbs free Fe (II). The collective results revealed the role of PAT1 in NA-Fe (II) absorption in the intestine and potential implication of NA in iron uptake in mammals.


Total Synthesis of Epilupinine: Synthetic Strategy of Fused Bicyclic Skeleton Containing Nitrogen


Synthesis and evaluation of 1,1,7,7-tetramethyl-9-azajulolidine (TMAJ) as a highly active derivative of N,N-dimethylaminopyridine


Development of a 1,3a,6a-triazapentalene derivatives as a compact and thiol-specific fluorescent labeling reagent


Synthesis and Antimicrobial Evaluation of Side-Chain Derivatives based on Eurotiumide A


Asymmetric Total Syntheses and Structure Elucidations of (+)-Eurotiumide F and (+)-Eurotiumide G

Asymmetric total syntheses of dihydropyran containing natural products, (+)-eurotiumide F and (+)-eurotiumide G have been described. These total syntheses revealed the absolute configuration of eurotiumide F and G, and confirmed the reported structure of eurotiumide F and revised the reported structure of eurotiumide G. Highlight of these syntheses is thermal rearrangement with 4-methoxyisochroman-1-one derivative having propargyl ether on phenolic ether under thermal condition to construct dihydropyran ring. X-Ray crystallographic analysis of (+)-eurotiumide G clarified the stereochemistry at the C1-position.


Organic Chemistry Research on the Mechanistic Elucidation of Iron Acquisition in Barley

An organic chemistry approach to the mechanistic elucidation of iron acquisition in graminaceous plants is introduced here. To elucidate this detailed mechanism using phytosiderophores, the efficient synthesis of 2'-deoxymugineic acid (DMA), a phytosiderophore of rice, was established. The synthetic DMA was confirmed to have similar iron transport activity to that of natural mugineic acid (MA). It was also revealed that the addition of synthetic DMA, along with iron, to a rice hydroponic solution enabled the rice to grow well even under an alkaline condition, and DMA clearly showed its high potential as a fertilizer to improve food production. On the other hand, the 2'-hydroxy group of MA was confirmed to serve as a point of introduction for labeling, allowing the synthesis of various mugineic acid derivatives as molecular probes. The incorporation of fluorescent mugineic acid into cells allowed them to be clearly observed by fluorescence confocal analysis, and this provided the first direct experimental evidence of transporter-mediated internalization of mugineic acid into cells.


Synthesis and Evaluation of 1,3a,6a-triazapentalene (TAP)-bonded system

A method of synthesizing a directly connected 1,3a,6a-triazapentalene (TAP) ring system as a linearly bonded aromatic system with a planar form was established. Various TAP-dimers and a 2-alkyl-TAP-trimer were synthesized and their fluorescence properties were evaluated. Although the direct connection of the TAP ring with other TAP rings did not affect the fluorescence properties in diluted solvent, TAP-dimers showed unique fluorescence properties derived from the aggregation state under highly concentrated conditions. In particular, TAP-dimer 5 f showed aggregation-induced emission in highly concentrated solution, and 5 b showed typical mechanochromic fluorescence in the solid state despite their compact molecular size.


Quantitation of sevourane in whole blood and aqueous solutions byvolatile organic compound sensing

Journal of Pharmacological and Toxicological Methods


Highly active and reusable hydrotalcite-supported Pd(0) catalyst for Suzuki coupling reactions of aryl bromides and chlorides


Development of 1,3a,6a-triazapentalene-labeled enterobactin as a fluorescence quenching sensor of iron ion


Synthesis of 2,6-Disubstituted-1,3a,6a-Triazapentalenes and Their Fluorescence Properties


Syntheses of 2-vinyl-2,3-dihydropyrroles and 3-methylene-1,2,3,4-tetrahydropyridines by palladium-catalyzed cyclization of N-tosyl imines with allylic diesters


The helical propensity of the extracellular loop is responsible for the substrate specificity of Fe(III)-phytosiderophore transporters.

Hordeum vulgare L. yellow stripe 1 (HvYS1) is a selective transporter of Fe(III)-phytosiderophores in barley that is responsible for iron acquisition from the soil. In contrast, maize Zea mays, yellow stripe 1 (ZmYS1) possesses broad substrate specificity. In this study, a quantitative evaluation of the transport activities of HvYS1 and ZmYS1 chimera proteins revealed that the seventh extracellular membrane loop is essential for substrate specificity. The loop peptides of both transporters were prepared and analysed by circular dichroism and NMR. The spectra revealed a higher propensity for α-helical conformation of the HvYS1 loop peptide and a largely disordered structure for that of ZmYS1. These structural differences are potentially responsible for the substrate specificities of the transporters.


Functional 1,3a,6a-triazapentalene scaffold: Design of fluorescent probes for kinesin spindle protein (KSP)

1,3a,6a-Triazapentalene is a compact fluorescent chromophore. In this study, triazapentalene was used to modify a series of biphenyl-type inhibitors of kinesin spindle protein (KSP) to develop fluorescent probes for the intracellular visualization of this protein. Microscopic studies demonstrated that these novel triazapentalene-labeled compounds exhibited inhibitory activity towards KSP in cultured cells and provided important information concerning the intracellular distribution.

Bioorganic & Medicinal Chemistry Letters


Effective Cellular Morphology Analysis for Differentiation Processes by a Fluorescent 1,3a,6a-Triazapentalene Derivative Probe in Live Cells

Nuclear and cytoplasmic morphological changes provide important information about cell differentiation processes, cell functions, and signal responses. There is a strong desire to develop a rapid and simple method for visualizing cytoplasmic and nuclear morphology. Here, we developed a novel and rapid method for probing cellular morphological changes of live cell differentiation process by a fluorescent probe, TAP-4PH, a 1,3a,6a-triazapentalene derivative. TAP-4PH showed high fluorescence in cytoplasmic area, and visualized cytoplasmic and nuclear morphological changes of live cells during differentiation. We demonstrated that TAP-4PH visualized dendritic axon and spine formation in neuronal differentiation, and nuclear structural changes during neutrophilic differentiation. We also showed that the utility of TAP-4PH for visualization of cytoplasmic and nuclear morphologies of various type of live cells. Our visualizing method has no toxicity and no influence on the cellular differentiation and function. The cell morphology can be rapidly observed after addition of TAP-4PH and can continue to be observed in the presence of TAP-4PH in cell culture medium. Moreover, TAP-4PH can be easily removed after observation by washing for subsequent biological assay. Taken together, these results demonstrate that our visualization method is a powerful tool to probe differentiation processes before subsequent biological assay in live cells.


Direct cyclization of 1,3-diaryl propargylic alcohols with dicarbonyl compounds by palladium-boric acid dual-catalyst system


Facile Guanidine Formation under Mild Acidic Conditions


Synthesis of functionalized 2,3-dihydropyrroles by oxidative radical cyclization of N-Sulfonyl β-enamino esters with alkenes


Palau'amine has received a great deal of attention in the past two decades as an attractive synthetic target by virtue of its intriguing molecular architecture and significant immunosuppressive activity. Here we report the total synthesis of palau'amine characterized by the construction of an ABDE tetracyclic ring core including a trans-bicylo[3.3.0]octane skeleton at a middle stage of total synthesis. The ABDE tetracyclic ring core is constructed by a cascade reaction of a cleavage of the N-N bond, including simultaneous formation of imine, the addition of amide anion to the resulting imine (D-ring formation) and the condensation of pyrrole with methyl ester (B-ring formation) in a single step. The synthetic palau'amine is confirmed to exhibit excellent immunosuppressive activity. The present synthetic route has the potential to help elucidate a pharmacophore as well as the mechanistic details of immunosuppressive activity.


Acid-catalyzed [4+3] cycloaddition reaction of N-nosyl pyrroles


Transgenic Petunia with the Iron(III)-Phytosiderophore Transporter Gene Acquires Tolerance to Iron Deficiency in Alkaline Environments

Iron is an essential nutrient for all plants. However, terrestrial plants often suffer from iron deficiency in alkaline soil due to its extremely low solubility. Alkaline soil accounts for about 30% of all cultivated ground in the world. Plants have evolved two distinct strategies, I and II, for iron uptake from the soil. Dicots and non-graminaceous monocots use Strategy I, which is primarily based on the reduction of iron(III) to iron(II) and the uptake of iron(II) by the iron-regulated transporter, IRT1. In contrast, graminaceous plants use Strategy II to efficiently acquire insoluble iron(III). Strategy II comprises the synthesis and secretion of iron-chelating phytosiderophores, such as mugineic acids and the Yellow Stripe 1 transporter proteins of the iron(III)-phytosiderophore complex. Barley, which exhibits the highest tolerance to iron deficiency in alkaline soil among graminaceous plants, utilizes mugineic acids and the specific iron(III)-mugineic acids transporter, HvYS1. In this study, we established the transgenic plant Petunia hybrida, which originally had only Strategy I, by introducing the HvYS1 transporter gene derived from barley. When the transgenic plants were grown hydroponically in media containing the iron(III)-2'-deoxymugineic acid complex, free 2'-deoxymugineic acid and its iron(III) complex were detected in the root extract of the transgenic plant by electrospray ionization-Fourier transform-ion cyclotron resonance mass spectrometry. The growth of the transgenic petunia was significantly better than that of the control host in alkaline conditions. Consequently, the transgenic plant acquired a significantly enhanced tolerance to alkaline hydroponic media in the presence of the iron(III)-2'-deoxymugineic acid complex. Furthermore, the flower color of the transgenic plant deepened. The results showed that iron-phytosiderophore complexes and their transporters can potentially be utilized to overcome the worldwide iron uptake problems to diverse plant species that are found in areas with alkaline conditions.


Synthesis of Yellow and Red Fluorescent 1,3a,6a-Triazapentalenes and the Theoretical Investigation of Their Optical Properties.


2'-Deoxymugineic acid promotes growth of rice (Oryza sativa L.) by orchestrating iron and nitrate uptake processes under high pH conditions

Poaceae plants release 2'-deoxymugineic acid (DMA) and related phytosiderophores to chelate iron (Fe), which often exists as insoluble Fe(III) in the rhizosphere, especially under high pH conditions. Although the molecular mechanisms behind the biosynthesis and secretion of DMA have been studied extensively, little information is known about whether DMA has biological roles other than chelating Fe in vivo. Here, we demonstrate that hydroponic cultures of rice (Oryza sativa) seedlings show almost complete restoration in shoot height and soil-plant analysis development (SPAD) values after treatment with 3-30 μm DMA at high pH (pH 8.0), compared with untreated control seedlings at normal pH (pH 5.8). These changes were accompanied by selective accumulation of Fe over other metals. While this enhanced growth was evident under high pH conditions, DMA application also enhanced seedling growth under normal pH conditions in which Fe was fairly accessible. Microarray and qRT-PCR analyses revealed that exogenous DMA application attenuated the increased expression levels of various genes related to Fe transport and accumulation. Surprisingly, despite the preferential utilization of ammonium over nitrate as a nitrogen source by rice, DMA application also increased nitrate reductase activity and the expression of genes encoding high-affinity nitrate transporters and nitrate reductases, all of which were otherwise considerably lower under high pH conditions. These data suggest that exogenous DMA not only plays an important role in facilitating the uptake of environmental Fe, but also orchestrates Fe and nitrate assimilation for optimal growth under high pH conditions.

The Plant Journal : for Cell and Molecular Biology


One-pot synthesis of tri- and tetrasubstituted pyridines by sequential ring-opening-cyclization-oxidation reaction of N-arylmethyl 3-aziridinylpropiolate esters

A novel strategy for the one-pot synthesis of substituted pyridines from N-arylmethyl 3-aziridinylpropiolate esters is described. The method employs a three-step procedure including the formation of allenyl imines, phosphine-catalyzed cyclization, and subsequent oxidation of the dihydropyridines. Depending on the reaction conditions of the final oxidation step, tri- and tetrasubstituted pyridines can be selectively produced.


N-Acyl-N-tosylhydrazine as a Synthon To Construct Tetrasubstituted Carbon Centers Possessing a Nitrogen Group


Synthesis of functionalized 2-vinyl-2,3-dihydropyrroles and 3-methylene-1,2,3,4-tetrahydropyridines by palladium-catalyzed cyclization of ß-enaminocarbonyl compounds with allylic bisacetates

The N-Heterocyclic carbene-catalysed oxidative carboxylation of arylaldehydes with water successfully proceeded when a sulfoxylalkyl-substituted imidazolium salt was used as the catalyst. The reactions can be run in the absence of oxidant, and a variety of arylaldehydes having an electron-withdrawing group were converted to the corresponding carboxylic acids.


Synthesis of substituted tetrahydrocyclobuta[b]benzofurans by palladium-catalyzed domino substitution-[2+2] cycloaddition of propargylic carbonates with 2-vinylphenols

Radical methods: The title reaction proceeds in the presence of a palladium catalyst to deliver substituted tetrahydrocyclobuta[b]benzofurans in a stereoselective manner. A radical mechanism is discussed.


Transformations of 1-(Oxiranylmethyl)-1,2,3-triazoles into 2-(Oxiranylmethyl)-1,2,3-triazoles and Alkanenitriles.


Total Synthesis of Manzacidins. An Overview and Perspective


Concise [4+3] cycloaddition reaction of pyrroles leading to tropinone derivatives

A concise [4+3] cycloaddition reaction of pyrroles with 2-(silyloxy)allyl cations has been developed. The oxyallyl cations stabilized with a methylthio group or geminal methyl groups were generated from the corresponding allylic alcohols under the influence of a Brönsted acid (Tf2NH), respectively. The use of N-nosyl-protected pyrroles as the four-carbon unit was found to give tropinone derivatives in high yield.


One-pot Synthesis of Highly Fluorescent 2,5-Disubstituted-1,3a,6a-triazapentalene.

A one-pot synthetic method was established for the preparation of 2,5-disubstituted-1,3a,6a-triazapentalenes. The fluorescence observation of the synthetic 2,5-disubstituted-1,3a,6a-triazapentalenes revealed that the introduction of a substituent at the C5 position allowed a substantial change in the fluorescence quantum yield with little effect on the fluorescence wavelength.


Hg(OTf)2-Catalyzed Vinylogous Semi-Pinacol Rearrangement Leading to 1,4-Dihydroquinolines.

An efficient method for the construction of dihydroquinoline derivatives possessing a quaternary carbon center is developed by an application of Hg(OTf)(2)-catalyzed vinylogous semi-pinacol-type rearrangement. The reaction was found to be specifically catalyzed by mercury salt and to proceed via a bicyclic aminal.


Carbon-Nitrogen Bond Formation Between Allyl Silyl Ether and Hydrazide Promoted by Mercuric Triflate Catalyst.


Direct Synthesis of Fluorescent 1,3a,6a-Triazazapentalene Derivatives via Click-Cyclization-Aromatization Cascade Reaction.

An efficient and versatile method was established for the preparation of 1,3a,6a-triazapentalenes. The 1,3a,6a-triazapentalene skeleton without an additional fused ring system was discovered to be a compact and highly fluorescent chromophore, which exhibited various interesting fluorescent properties such as a noteworthy correlation of luminescent wavelength with the Hammett ς(p) value and a strongly positive solvatofluorochromism.

Journal of the American Chemical Society


Mugineic acid derivatives as molecular probes for the mechanistic elucidation of iron acquisition in barley.


Synthetic Studies on Palauamine. Construction of the Cyclopentane Core via an Asymmetric [1,3]-Dipolar Cycloaddition.

The cyclopentane core of palau'amine has been constructed in optically pure form through the use of an asymmetric azomethine ylid [1,3]-dipolar cycloaddition reaction.


Development of Practical Synthetic Method toward Mechanistic Elucidation of Biologically Active Natural Products

生物活性天然有機化合物の機能解明を指向した実践的合成手法の開発

The limited supplies of biologically active natural products from natural source have been a severe bottleneck for their application to medical care or mechanistic study of their functions. Synthetic organic chemistry may become a best possible solution of this supply problem by the development of practical synthetic methods suited to the intended molecules. For right-half of halichondrin B, we established a new catalytic cycle of Cr-mediated coupling reaction, new asymmetric Ni/Cr-mediated coupling reaction, surprisingly efficient catalytic Cr-mediated coupling reaction, catalytic Ni/Cr-mediated macrocyclization without use of high-dilution techniques, and effective device for forming polycyclic ring system of halichondrin B. For mugineic acid, we established the practical synthesis of 2'-deoxy mugineic acid with minimal requirements for workup and purification procedure, efficient synthesis of mugineic acid, and synthesis of mugineic acid derivatives as molecular probes. For E-ring of palau'amine, we established Hg(OTf)2-catalyzed olefin cyclization reactions, and its application to the construction of tetra-substituted carbon center possessing nitrogen that corresponds to C16 position of palau'amine.

Journal of Synthetic Organic Chemistry, Japan


Hg(OTf)2-BINAPHANE-Catalyzed Enantioselective Anilino Sulfonamide Allyl Alcohol Cyclization.


Hg(OTf)2-Catalyzed Cycloisomerization of Aryl- and Hetero- Substituted 1,3-Dienes.


Toward Mechanistic Elucidation of Iron Acquisition in Barley: Efficient Synthesis of Mugineic Acids and Their Transport Activities.

Iron acquisition of graminaceous plants is characterized by the synthesis and secretion of iron-chelating compounds, mugineic acids (MAs), and by a specific uptake system for MAs-iron(III) complexes. We identified a transporter, HvYS1 (Hordeum vulgare L. yellow stripe 1), that is highly specific for MAs-iron(III) in barley roots. In this article we outline the characterization of HvYS1, and our recent work on the practical syntheses of MAs and investigations into the molecular basis of the specific transport of their iron(III) complexes by HvYS1. 2'-Deoxymugineic acid (DMA) was synthesized in a good overall yield from commercially available Boc-l-allylglycine using a minimal number of short simple operations with minimal protecting groups and work-up/purification procedures. The same strategy was also successfully applied to beta-hydroxy-l-allylglycine, which was obtained by an allylic oxidation of l-allylglycine derivatives, to give MA and 2'-epi-MA efficiently. HvYS1 transported the iron(III) complexes of all three synthetic specimens with efficiency similar to that of a natural mugineic acid complex. With sufficient quantities of MAs in hand, we analyzed the function of HvYS1 and revealed by preparing chimeric transporters that the sixth outer membrane loop of the transporter plays a vital role in substrate specificity.


4-Aminopyridines-Catalyzed Direct and Regioselective Acylation of N-Tosylhydrazide

An efficient and simple method for selective acylation of either one of two nitrogen atoms of tosylhydrazide was developed. The selectivity was drastically controlled by a catalytic amount of 4-aminopyridine or 4-(dimethylamino)pyridine with common acylating agents. The nitrogen atom masked with a tosyl group was acylated in the presence of 4-aminopyridine, whereas the primary nitrogen atom was acylated in the absence of 4-aminopyridine.


Toward Palauamine; Hg(OTf)2-Catalyzed Synthesis of Cyclopentane Core.


Attempts to Improve the Overall Stereoselectivity of Ireland-Claisen Rearrangement

With focus on the steric effects present in the transition states for the [3,3]-sigmatropic rearrangement, the substrate 5 has been designed to improve the overall stereoselectivity of the Ireland-Claisen rearrangement. Experimentally, it has been found that (1) only Z-6 rearranges to 7 at 80 degrees C and (2) E-6 isomerizes to Z-6 at 80 degrees C, thereby allowing the transformation of 5 into 7 in an almost quantitative yield. To illustrate the usefulness of this approach, two additional examples are given.


Hg(OTf)2-Catalyzed Instantaneous Hydration of β- and δ-Hydroxy Internal Alkynes with Complete Regioselectivity


Silaphenylmercuric Triflate-Catalyzed Reactions: The First Solid Supported Mercuric Salt Catalyst.

Let it flow, let it flow: A procedure to generate the first solid-supported mercuric salt, silaphenylmercuric triflate, is described. Silaphenylmercuric triflate showed remarkable catalytic activity for an indole synthesis, furanoyne cyclization, arylyne cyclization, and tandem carbocyclizations. An efficient flow reaction system for indole synthesis and arylyne cyclization is also described (see figure).


Novel Hg(OTf) 2-catalyzed arylene cyclization was achieved with highly efficient catalytic turnover (up to 200 times). The reaction takes place via protonation of allylic hydroxyl group by in situ formed TfOH of an organomercuric intermediate to generate a cationic species. Subsequent smooth demercuration regenerates the catalyst.


Efficient Glycosylation Using ODS Adsorption Method Based on the Affinity of Long Alkoxybenzyl Glycoside.


Hg(OTf)2-Catalyzed Cyclization of N-Tosylanilinoallylic Alcohols to 2-Vinylindolines


A specific transporter for iron (III)-phytosiderophore complex involved iron acquisition by bareley roots.


Virtually Complete E-Selective -Unsaturated Ester Synthesis by Hg(OTf)2-Catalyzed Hydration of sec-Ethoxyalkynyl Acetate.

The reaction of alkyl-substituted sec-ethoxyalkynyl acetates with water catalyzed by Hg(OTf)2 afforded alpha,beta-unsaturated esters in excellent yield with high catalytic turnover up to 1000 times under very mild reaction conditions with virtually complete E-selectivity, superior even to that of the HWE reaction.


Catalytic Activation of the Leaving Group in the SN2 Reaction.

A novel catalytic activation of the leaving group in the S(N)2 reaction is achieved as an extension of our mercuric triflate-catalyzed reactions. Derivatives of anilinoethyl 4-pentynoate reacted smoothly with catalytic amounts of Hg(OTf)(2) to give indoline derivatives in excellent yield with efficient catalytic turnovers under very mild conditions. The reaction of optically pure secondary alcohol derivatives resulted in inversion of stereochemistry, which is a definitive feature of the S(N)2 reaction. The procedure is applicable for benzoazepine synthesis.


Structural element responsible for the Fe(III)-specific transport as phytosiderophore complex by HvYS1 transporter of barley.

Hordeum vulgare L. yellow stripe 1 (HvYS1) is a selective transporter for Fe(III)-phytosiderophores, involved in primary iron acquisition from soils in barley roots. In contrast, Zea mays yellow stripe 1 (ZmYS1) in maize possesses broad substrate specificity, despite a high homology with HvYS1. Here we revealed, by assessing the transport activity of a series of HvYS1-ZmYS1 chimeras, that the outer membrane loop between the sixth and seventh transmembrane regions is essential for substrate specificity. Circular dichroism spectra indicated that a synthetic peptide corresponding to the loop of HvYS1 forms an alpha-helix in solution, whereas that of ZmYS1 is flexible. We propose that the structural difference at this particular loop determines the substrate specificity of the HvYS1 transporter.


Synthesis and Absolute Structure of Manzacidin B

[reaction: see text] Four possible stereoisomers of manzacidin B were synthesized using stereochemically defined synthetic routes via the azide 7 and oxazoline 11 starting with the (R)-alpha-methyl Garner aldehyde 5. Comparisons of the spectroscopic data of the synthetic isomers 4a-d with those of the natural manzacidin B revised the proposed structure 3 to (4S,5S,6R)-4d.


A Practical Synthesis of a Phytosiderophore 2-Deoxymugineic Acid. A Key to the Mechanistic Study of Iron Acquisition by Graminaceous Plants


Total synthesis and morphogenesis-inducing activity of (±)-thallusin and its analogues.


On the Stereoselectivity of Asymmetric Strecker Synthesis in a Cyclohexane System: Synthesis of Optically Active Cis- and Trans-1-amino-2-hydroxycyclohexane-1-carboxylic Acids.

Bulletin of the Chemical Society of Japan


Surprisingly Efficient Catalytic Cr-Mediated Coupling Reactions.

[reaction: see text] With use of 1 mol % of Cr catalyst 5, surprisingly efficient Cr-mediated couplings of aldehydes with various types of nucleophiles have been realized. The catalyst set of Cr catalyst 5 and Ni catalyst 4 is used for alkenylation, alkynylation, and arylation, whereas the catalyst set of Cr catalyst 5 and CoPc (cobalt phthalocyanine) is used for 2-haloallylation, alkylation, and propargylation. Only the Cr catalyst 5 is required for allylation. The reaction rates in DME and THF have been found significantly faster than that in MeCN.


A New Method for Translating the Asymmetric Ni/Cr-Mediated Coupling Reactions from Stoichiometric to Catalytic.

[reaction: see text] A new method has been developed for effectively translating the degree of asymmetric induction and the chemical yield achieved in the stoichiometric asymmetric Ni/Cr-mediated coupling to a catalytic asymmetric process via a chiral sulfonamide ligand. It has also been shown that the Ni catalyst plays a central role. Among a number of the Ni catalysts, the 2,9-dimethylphenanthroline/NiCl(2) complex (7) has been found to be the most effective.


Catalytic Ni/Cr-Mediated Macrocyclization without Use of High-Dilution Techniques.

The feasibility of catalytic Ni/Cr-mediated macrocyclization was demonstrated for the two substrates chosen from the halichondrin area. With 5 mol % of Ni and Cr catalysts, the macrocyclization was realized without use of high-dilution techniques. The reported method has a number of appealing features, including user-friendliness, easy workup, apparent scalability, and cost-effectiveness. In addition, all the required reagents are commercially available or obtainable in one or two steps from commercially available chemicals.

Journal of the American Chemical Society


New Catalytic Cycle for Couplings of Aldehydes with Organochromium Reagents.

[reaction: see text] A new catalytic cycle has been developed to effect all three subgroups of Cr-mediated couplings, i.e., (1) Ni/Cr-mediated alkenylation, alkynylation, and arylation, (2) Co/Cr-mediated 2-haloallylation, alkylation, and propargylation, and (3) Cr-mediated allylation. In the presence of chiral sulfonamide ligands, good asymmetric inductions can be achieved for some of the Ni/Cr-mediated alkenylation, Co/Cr-mediated 2-haloallylation and propargylation, and Cr-mediated allylation.


A Simple but Remarkably Effective Device for Forming the C8-C14 Polycyclic Ring System of Halichondrin B.

A simple device consisting of two ion-exchange columns, two alumina-based filters, and a pump (Figure 1) was assembled to form the C8-C14 polycyclic ring system present in the halichondrin B class of marine natural products. The effectiveness of this device was tested for three substrates. In each case, the desired polycyclic ketal 3, 5, or 7 was obtained almost quantitatively in a single operation.


Stereocontrolled Synthesis of a Potent Agonist of Group II Metaabolropic Glutamate Receptors, (+)-LY354740, and its Related derivatives.


Efficient Synthesis of Optically Active α-Substituted Glutamate Analogs Possessing α-Hydroxymethyl and α-Alkoxymethyl Groups.


Efficient Synthesis of EDO-S,S-DMEDT-TTF, a Potent Organic-Donor for Syntheti Metals.


Novel and Efficient Transformation of -Amino Nitrile to -Imino and -Amide Nitriles in Asymmetric Strecker Synthesis.


Total Synthesis and Absolute Structure of Manzacidin A and C.


Asymmetric synthesis of 5- and 6-Membered Carbocyclic Serine Analogs via an Intramolecular Strecker Synthesis.