One-pot Tandem Coupling Method for the Short Step Formal Synthesis of Riccardin C

One-pot reactions reduce reagent amounts and circumvent process treatments, such as work-up and purifications in multi-step reactions. In this study, we achieved the formal total synthesis of riccardin C through a one-pot reaction by simultaneously linking four units through two Sonogashira coupling reactions and one Suzuki coupling reaction, followed by reduction and deprotection. Thus, this one-pot method comprised five steps and did not require the purification of intermediate reaction mixtures, which saves resources, such as reagents and solvents, and expedites the work process.


Practical Method for Hydroxyl-Group Protection Using Strontium Metal and Readily Available Silyl Chlorides

We have found that the etherification of silyl-protected secondary alcohols proceeds smoothly in the presence of strontium metal using silyl chloride instead of the expensive, yet more reactive, and commonly used silyl triflate. The reaction occurred almost completely with various alcohols.


Chemoselective Ketone Synthesis by the Strontium-mediated Alkylation or Arylation of N,N-Dimethylamides or Urea


Three-component, one-pot tandem Sonogashira/Suzuki-Miyaura coupling reactions for the synthesis of a library of ceramide-transport protein inhibitors that were designed in silico

We have developed a onepot, tandem Sonogashira/SuzukiMiyaura coupling reaction, which is unknown synthetically, and applied it for the synthesis of a library of potential natural ligand nonmimetic inhibitors of the lipidtransfer protein, ceramidetransport protein (CERT). The characteristic feature of this reaction is that the twostep coupling reaction proceeds smoothly with only 5 mol% of palladium catalyst. Furthermore, the location of the formed carboncarbon bond would be strictly defined because of the difference in reactivity. Therefore, many derivatives could be synthesized in high yields without the formation of regioisomeric byproducts by the same procedure. We also performed a semigram scale synthesis of several derivatives to provide the bioactive assey. After synthesizing as many as 113 derivatives, we identified a nonnatural mimetic inhibitor with activity comparable to that of the known inhibitor (1R,3S)-HPA-12.


Cocrystal Structure of the Redox-active Phenylenediamine and Quinonediimine Derivatives


Methoxycarbonyl Group as a Conformational Regulator for the Benzene Ring of Triphenylamines


Aerobic oxidation of alcohols using bismuth bromide as a catalyst

We developed an environmentally friendly method for aerobic oxidation of alcohols using a commercially available, relatively benign bismuth salt as a catalyst. We found that the catalytic combination of BiBr3 with nitric acid is key for enhancing the reactivity. The reaction proceeds well under air, making the use of pure oxygen unnecessary. Each of the primary or secondary alcohols tested was oxidized to the corresponding aldehydes or ketones using this protocol.


Environmentally Benign Ritter Reaction Using Bismuth Salt as a Catalyst

We developed the environmentally benign Ritter reaction using commercially available, less harmful bismuth salt as a catalyst. The reaction proceeded smoothly even using stoichiometric amount of nitrile to alcohol without any solvents. We also succeeded in establishing a purification process without using any organic solvents.


Strontium-mediated selective protonation of unsaturated linkage of aromatic hydrocarbons and these derivatives


Cytometric analysis on cytotoxicity of 4,4 -methylenediphenyl diisocyanate, a chemical allergen, in rat thymocytes

4,4'-Methylenediphenyl diisocyanate (MDI) is a cross-linking agent. Chemical reactivity of MDI with endogenous substances such as albumin and glutathione (GSH) is assumed to be responsible for MDI toxicity. We examined the cytotoxic effect of MDI on rat thymocytes, under the condition that endogenous biological substances except for cells were nominally absent, in order to study chemico-biological interactions between MDI and cells. The treatment of 10 50 µM MDI for 3 h significantly increased the side scatter signal intensity of cytograms, without affecting forward scatter intensity. The increase in side scatter signal intensity by MDI was associated with an increase in cell lethality. The treatment of cells with 50 µM MDI for 3 h increased cell lethality without increasing the population of pre-apoptotic annexin V-positive living cells. In contrast, H2O2 at 100 µM significantly increased the population of annexin V positive living cells prior to cell death. MDI at 30 50 µM did not affect the increase in cell lethality induced by H2O2 or A23187. Simultaneous application of 50 µM GSH did not affect the cytotoxicity of 50 µM MDI. It was therefore concluded that the process of cell death induced by MDI could not be attributed to oxidative stress and intracellular Ca2+ overload, and that MDI possesses cytotoxic actions that are not significantly related to its chemical reactivity with GSH.


Superior Alkylating Agents for Bulky Esters/Ketones via Strontium-Mediated Barbier-Type Reaction


Depolymerization of Waste PET with Phosphoric Acid-Modified Silica Gel Under Microwave Irradiation


Yttrium decreases the intracellular Zn2+ concentration in rat thymocytes by attenuating a temperature-sensitive Zn2+ influx

Yttrium is used in the production of various electronic devices because the alloy it contains enhances or modifies the properties of other elements. In order to study the cytotoxic action of yttrium, the effect of yttrium chloride (YCl3) on the intracellular Zn2+ level was examined in rat thymocytes using a flow cytometer with FluoZin-3-AM and propidium iodide. The application of YCl3 significantly decreased the intensity of the FluoZin-3 fluorescence, suggesting a decrease in the intracellular Zn2+ level or quenching of the FluoZin-3 fluorescence by Y3+. However, since Y3+ did not attenuate the FluoZin-3 fluorescence under cell-free conditions, the latter suggestion was ruled out. Rat thymocytes possess a temperature-sensitive membrane pathway that carries Zn2+ into the cells. The application of YCl3 attenuated the FluoZin-3 fluorescence augmented by externally applied ZnCl2 in a concentration-dependent manner. This suggested that Y3+ inhibited the Zn2+ influx, resulting in the decrease in the intracellular Zn2+ level. Yttrium may induce dyshomeostasis of intracellular Zn2+, leading to some cytotoxic actions.

Environmental Toxicology and Pharmacology


Some characteristics of membrane Cd2+ transport in rat thymocytes: An analysis using Fluo-3

Although cadmium-induced apoptosis of lymphocytes is one of common features in the immunotoxicity of cadmium, the membrane pathway for intracellular cadmium accumulation is not fully elucidated. To characterize membrane Cd2+ transport of rat thymocytes, the change in intracellular Cd2+ concentration under various conditions was examined by the use of Fluo-3, a fluorescent probe for monitoring the change in intracellular concentration of divalent metal cations. The membrane Cd2+ transport was estimated by the augmentation of Fluo-3 fluorescence induced by bath application of CdCl2. Lowering temperature strongly suppressed the augmentation of Fluo-3 fluorescence by CdCl2, suggesting that the metabolic process can be involved in membrane Cd2+ transport. External acidification (decreasing pH) and membrane depolarization by adding KCl attenuated the augmentation, indicating the requirement of electrochemical driving force for membrane Cd2+ transport into the cells. Bath application of CaCl2 and ZnCl2 equally decreased the augmentation, suggesting their competition with Cd2+ at the membrane transport. The augmentation by CdCl2 was lesser in the cells treated with N-ethylmaleimide inducing chemical depletion of cellular thiols. The result suggests the contribution of sulfhydryl groups to membrane Cd2+ transport. Taken together, it is suggested that the cells possess a temperature-sensitive membrane Cd2+ pathway, driven by electrochemical gradient of Cd2+ and transmembrane potential, with competitive binding site. Based on the characteristics described above, it is unlikely that the membrane Cd2+ transport in rat thymocytes is attributed to a single transport system although it has characteristics that are similar to those of divalent cation transporter 1.


スチレン類二量化に有効な鉄シリカ触媒のXAFS法による構造解析

スチレン類二量化に有効な鉄シリカ触媒のXAFS法による構造解析

α-メチルスチレン二量化反応に活性を示す鉄ゾル-ゲル法にて調製した鉄シリカ触媒をX線回折およびX線吸収分光法により評価した．触媒中鉄種の存在状態は仕込みSi /Fe 比に依存し，100 以上では四面体FeOxCl4-x種，50以下ではα-Fe2O3 凝集種が主成分であり，その存在比をXANES解析により求めた．シリカマトリクスに捕捉された孤立FeOxCl4-x が活性種として機能し，固体酸性質を発現する機構について論じた．

Advances in X-Ray Chemical Analysis, Japan


The Development of the New Synthetic Methods Using Metallic Strontium

金属ストロンチウムを用いる新しい合成手法の開発

We found the interesting results that alkylation of carboxylic acids with methyl iodide using strontium metal proceeded smoothly to afford the corresponding monomethylated ketones, rather than the dimethylated alcohols, preferentially in moderate to good yields. Using the carboxylic acid sodium salt, the yield decreases slightly, but the reaction controls the over-addition of methyla-ting agent to give the dramatically improvement with high selectivities. Next, when benzoic acid reacted with metallic strontium and alkyl iodides, the unexpected reactions occurred to give p-alkylated products of the aromatic ring of benzoic acid in a trace amount. We were interested in the p-allylated product because this allylation reaction is unusual in these conditions and there are only a few reports of the p-alkylation of aromatic carbonyl compounds. As the results of various investigations, the p-alkylated products were obtained predominantly in good yields. Furthermore, it was found that the convenient bulky tert-benzylic alcohol benzoates were prepared by the dialkylation of methyl benzoate with methyl or i-butyl iodide in the presence of metallic strontium, followed by the addition of benzoyl chloride, benzoic anhydride or acetic anhydride as two portions.

Journal of Synthetic Organic Chemistry, Japan


A Highly Efficient Carbon-Carbon Bond Formation Reaction via Nucleophilic Addition to N-Alkylaldimines without Acids or Metallic Species

A nucleophilic addition reaction to N-methylaldimines without acid or metal species is described. A novel reagent, dicyanomethyl acetate, is used as a nucleophile to give alpha-(N-methyl-N-acetyl)amino acid methyl esters in excellent yield.

Journal of the American Chemical Society


Synthesis of a water-soluble molecular tweezer and a recognition study in an aqueous media


Cytometric analysis on adverse action of diphenyl ditellurde on rat thymocytes: Cell shrinkage as cytotoxic parameter

細胞萎縮を細胞毒性の指標として，有機テルル化合物の毒性評価を行った．ジフェニル·ジテルライドはサブマイクロ濃度でラット胸腺細胞の細胞内カルシウムイオン上昇させ，カスパーゼ依存性にアポトーシスを誘発することが明らかになった．よって，有機テルル化合物の使用·処分には注意を要することが示唆された．


A convenient procedure for bismuth-mediated Barbier-type allylation of aldehydes in water containing fluoride ions.

A new and convenient procedure for synthesis of homoallylic alcs. in generally good to excellent yields has been developed. The bismuth-mediated Barbier-type allylation of aldehydes (arom., aliph., alicyclic and heterocyclic) with allyl bromide has been carried out in water in the presence of fluoride ions.


Highly efficient chiral resolution and determination of absolute configuration of 2-alkanols by using a cyclopenta[b]furan derivative.

The reaction of 3a-benzhydryl-3,3a,4,5-tetrahydro-2H-cyclopenta[b]furan and various 2-alkanols in the presence of a catalytic amt. of pyridinium 4-toluenesulfonate in dichloromethane gave 3a-benzhydryl-6a-(1-methyl-alkoxy)-hexahydrocyclopenta[b]furan in more than 90% chem. yields. The resulting diastereomeric mixt. is easily separable on silica gel chromatog. because of the large Rf value (briefly 0.1). Abs. configuration of the 2-alkanols can be easily estd. by the chem. shifts of 1H and 13C NMR of methyne group of the benzhydryl moiety.


The Barbier-type alkylation of aldehydes with alkyl halides in the presence of metallic strontium.

In the presence of metallic strontium, the Barbier-type alkylation of aldehydes with alkyl iodides proceeded smoothly to afford secondary alcs., e.g., I, in moderate to good yields. The unusual addn. reaction of Et benzoate with tert-Bu iodide gave 4-tert-butylbenzoate in good yield. Using strontium isopropoxide, the Meerwein-Ponndorf-Verley-type redn. of the aldehyde proceeded smoothly under reflux conditions in 2-propanol.

Bulletin of the Chemical Society of Japan


4) A Convenient One Pot Allylation of Aldehydes with Allylic Halides Prepared in situ from Allylic Alcohols in the Presence of Metallic Bismuth


Methylmercury toxicity in rat brain neurons: modificatons by compounds possessing SH-group and comparison with dimethylmercury, N-ethylmaleimide, and ionomycin

Environmental Toxicology and Pharmacology


Effects of triphenyltin on growth and viability of K562 leukemia cells


A Grignard-Type Addition of an Allyl Unit to Carbonyl Compounds Containing a Carboxyl Group by Using BiCl3-Zn(0)-Allyl Bromide.

In the presence of BiCl3-Zn(0), nearly equimolar amts. of allyl bromide reacted with carbonyl compds. contg. a carboxyl group to afford the corresponding homoallylic alcs. having a carboxyl group or the intramol. dehydrated lactones in good yields.


Asymmetric trimethylsilylcyanation of aldehydes utilizing chiral bismuth compounds. A frontier in bismuth mediated synthetic reactions.

Bismuth(III) chloride (BiCl3) was found to work efficiently as a versatile catalyst for cyanation of aldehydes with trimethylsilyl cyanide to afford the corresponding cyanohydrins in high yields. Triphenylbismuthan (Ph3Bi) is also effective. The reaction has been applied to the asym. cyanation of a variety of aldehydes in high yields with moderate to good enantioselectivities by use of a chiral bismuth catalyst prepd. in situ from BiCl3 and (2R,3R)-(+)-diethyl tartrate.


Regioselective allylation of ketenes promoted by SmI2.

Ketenes react with various allylic halides mediated by 2 equiv SmI2 to afford allylated ketones in good yields. In the reaction with -substituted allylic halides, the regioselectivity is influenced by the olefinic geometry of allylic halides. By using -substituted (E)-allylic halides, allylation occurs predominantly at the less hindered site ( -position) of allylic groups and the tendency was enhanced by the addn. of HMPA.


Enantioselective protonation of samarium enolates by a C2-symmetric chiral diol.

High enantioselectivity (up to 97% ee) has been achieved in the protonation of samarium enolates which were generated by SmI2-mediated cross-coupling reaction between unsym. dialkylketenes and allyl iodide, using C2-sym. chiral diol (S,S)-o-C6H4(CH2OCH2CHPhOH)2 as a proton source. The stereochem. of enolate formation and of the enantioselective protonation is discussed.


Asymmetric synthesis of benzoin by samarium diiodide-mediated enantioselective protonation.

Samarium (Z)-1,2-diphenylethen-1,2-diolate, which is considered to be an intermediate of a SmI2-mediated redn. of benzil, was protonated enantioselectively by quinidine to afford (R)-benzoin in 91% ee. It was found that quenching the unreacted enediolate with oxygen was crucial to obtain high enantioselectivity. The configuration of the samarium enediolate was confirmed by isolating (Z)-O,O'-diacetyl-1,2-diphenylethen-1,2-diol.


Asymmetric reactions. XVI. Asymmetric synthesis of a piperazine alkaloid.

Piperazine alkaloid, (2S,5S)-2,5-dibenzyl-1,4-dimethylpiperazine (I) was synthesized by redn. of (3S,6S)-3,6-dibenzyl-1,4-dimethyl-2,5-piperazinedione which was prepd. by a catalytic asym. hydrogenation of the corresponding 3,6-dibenzylidene deriv.


Cytotoxic action of tri-n-butyltin hydride, a nucleaphilic triorganotin, on rat thymocytes: a flow cytometric study


Effects of organic and inorganic mercuries on growth and viability of K562 human leukemia cells


The Convenient and Useful Esterification of Bulky Tertiary Alcohols Using Strontium Compounds


Reductive Self-coupling Reaction of Imines and Aldehydes Induced by Strontium Metal


A New Synthetic Method for Para Alkylation of Benzoic Acids Using Metallic Strontium and Alkyl Iodide


A New Synthetic Method for Methyl Ketones from Carboxylic Acids Using Metallic Strontium and Methyl Iodide


The Chemistry of Alkylstrontium Halide Analogue Part 2: Barbier-Type Dialkylation of Esters with Alkyl Halides


The Chemistry of Alkylstrontium Halide Analogues: Barbier-type Alkylation of Imines with Alkyl Halides


Solvent-free Imino-Aldol Three-component Couplings on a Conveniently-prepared and Reusable Phosphoric Acid-Silica Gel Support


Water Accelerated Allylation of Aldehydes by Using Water Tolerant Grignard-Type Allylating Agents from Allylmagnesium Chloride and Various Metallic Salts

Some water-tolerant allylating agents prepared in situ from allylmagnesium chloride and bismuth trichloride, tin tetrachloride, tin dichloride, antimony trichloride, indium trichloride, or nickel dichloride reacted with aldehydes in THF-H2O to afford the desired homoallylic alcohols in good yields. The present reaction proceeded more smoothly than that under non-aqueous media.

アリルGrignard試薬と三塩化ビスマス，四塩化スズ，二塩化スズ，三塩化アンチモン，三塩化インジウム及び二塩化ニッケルから調製したアリル化試剤は水に安定であり，アルデヒドと速やかに反応し対応するホモアリリックアルコールを高収率で与える．本反応は非水条件下より，含水条件下の方が反応は速やかに反応する．


Organic Solvent-Free One-Pot Reduction of Imines Generated in situ from Aldehydes and Aniline by Tributyltin Hydride on Silica Gel

Imines generated in situ from aldehydes and aniline can be reduced using tributyltin hydride on silica gel under solvent-free conditions to provide te corresponding amines in good yields.

アルデヒドとアニリンから反応系中で調製したイミンは無溶媒中固体シリカゲル上でトリブチルスズヒドリドを用いると容易に還元でき，対応するアミンを高収率で得られることが出来る．


Bismuth Trichloride Catalyzed Efficient Reductive Etherification of Carbonyl Compounds with Alcohols: A Novel Method for Preparation of Symmetrical and Unsymmetrical Ethers

The reductive homocoupling of a carbonyl compound and heterocoupling of a carbonyl compound with a non-protected alcohol were both effected smoothly at room temperature with triethylsilane in the presence of a catalytic amount of bismuth trichloride to afford the corresponding ethers in good yields.

カルボニル化合物同士の還元的ホモカップリングやカルボニル化合物と無保護のアルコールとの還元的ヘテロカップリング反応は，触媒量の三塩化ビスマスとトリエチルシランを用いる事により，対応するエーテルを高収率で得ることが出来る．


A novel aqueous Barbier-Grignard-type allylation of aldehydes in a Mg/BiCl3 bimetallic system.

In the presence of BiCl3-Zn(0), nearly equimolar amts. of allyl bromide reacted with carbonyl compds. contg. a carboxyl group to afford the corresponding homoallylic alcs. having a carboxyl group or the intramol. dehydrated lactones in good yields.


The cross-coupling reaction of aldehydes with -diketones by the use of bismuth trichloride and metallic zinc.

In the presence of bismuth trichloride and metallic zinc, -diketones react with aldehydes in THF under reflux to afford the corresponding , -dihydroxy ketones in moderate to good yields. The reaction takes place even in aq. media.


The SmI2 mediated cross-coupling reaction of aldehydes with a-diketones in their aqueous forms.

By the use of samarium diiodide (SmI2), a cross-coupling reaction of aldehydes with -diketones smoothly proceeds in the presence of water to give the corresponding adducts in moderate to good yield. Thus, cross-coupling reaction of MeCOCHO with PhCH2CHO in THF and H2O contg. SmI2 gave 39:61 isomeric ratio of anti- and syn-PhCH2CHOHCHOHCOMe in 64% yield. In this reaction, it is possible to use the substrates such as phenylglyoxal monohydrate, aq. methylglyoxal, formalin, and aq. -chloroacetaldehyde.


A facile synthesis of 2,3-dihydroxy ketones from 1,2-diketones and aldehydes using samarium diiodide.

In the presence of samarium diiodide, 1,2-diketones R1COCOR2 react with aldehydes R3CHO in THF to afford the corresponding 2,3-dihydroxy ketones anti- and syn-R3CH(OH)CR1(OH)COR2 (e.g., R1 = R2 = Me, R3 = PhCH2CH2) in good yields with moderate diastereoselectivity (anti preferred). The reaction of unsym. 1,2-diketones with aldehydes gives the products with high regioselectivities.


Asymmetric synthesis of ketones by samarium diiodide-mediated allylation or benzylation of ketenes followed by enantioselective protonation.

SmI2-mediated allylation or benzylation of alkyl aryl ketenes followed by enantioselective protonation with (S,S)-o-[PhCH(OH)CH2OCH2]2C6H4 gave the corresponding ketones in 61-91% ee.


The addition reaction of -keto carboxylic acids to olefinic compounds by the use of Mn(III) tris(2-pyridinecarboxylate) as an oxidant.

Intermol. addn. reactions of radical species generated from -keto carboxylic acids to olefinic compds. such as a silyl enol ether, a ketene dithioacetal and an enamine proceed selectively by the use of manganese(III) tris(2-pyridinecarboxylate) (I) as an oxidant. E.g., BzCHMeCH2Bz was obtained in 70% yield from reaction of BzCHMeCO2H with PhC(:CH2)OSiMe3 in DMF in the presence of I.


Kinetic resolution of -arylcarboxylic acid derivatives by a catalytic use of a chiral titanium alkoxide.

Kinetic resoln. of racemic -aryl carboxylic acids is successfully achieved by a catalytic use of Ti(OCHMe2)4 and a chiral 1,4-diol in the reaction of the corresponding 2-pyridinethiol esters and Me2CHOH. Thus, reaction of ( )-EtCHPhCOSR (R = 2-pyridyl) with 10 mol. % Ti(OCHMe2)4, 11 mol. % diol I, and 5 equiv Me2CHOH in PhMe gave 69% (based on 1/2 equiv of the thio ester) (R)-EtCHPhCO2CHMe2.


An efficient and convenient method for the asymmetric allylation of aldehydes with allyltrimethylsilane catalyzed by diphenylboryl triflate.

Using catalytic amts. of diphenylboryl triflate, aldehydes reacted with (S)-1-phenyl-1-trimethylsilyloxyethane and Me3CSiCH2CH:CH2 to give the chiral homoallyl ethers,e.g., PhCH2O(CH2)2CH(OCHMePh)CH2CH:CH2, in good yields with high stereoselectivities.


An efficient method for the kinetic resolution of cyclic dl-dicarboxylic anhydrides catalyzed by diphenylboryl triflate.

In the presence of CF3SO3BPh2, the kinetic resoln. of cyclic d1-dicarboxylic anhydrides is effectively achieved by (R)-PhCH(OBPh2)CH2OMe as the chiral source.


A facile method for the oxidation of aldehydes to carboxylic acids via acetal-type diperoxides.

In the presence of a catalytic amt. of Ph3CClO4, RCHO [R = Ph, PhCH2CH2, PhCH2OCH2CH2, CH2:CH(CH2)8, 2-BrC6H4, 4-MeSC6H4] react with Me3SiOOCMe3 to give RCH(OOCMe3)2 (I) in good yields. Reactions of I with piperidine at 90 or with aq. CuSO4 and L-ascorbic acid at room temp. gave RCO2H in good yields.


A novel and useful method for the preparation of methyl esters from dimethyl acetals.

In the presence of a catalytic amt. of trityl perchlorate, acetal-type peroxides RCH(OMe)OOCMe3 [R = PhCH2, Ph(CH2)2, PhCHMe, octyl, nonyl, CH2:CH(CH2)8] were prepd. from di-Me acetals and Me3COOSiMe3 in 85-90% yields. The peroxides were then converted to the corresponding Me esters in 84-94% yields by pyrolysis.