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Biomedical subjects

Masataka Ihara

Publications and source records attributed to Masataka Ihara.

At least 19 recordsLinked to original sources
PubMed2006

Synthesis of three classes of rhodacyanine dyes and evaluation of their in vitro and in vivo antimalarial activity.

Selected members of three classes of rhodacyanine dyes, [0,0]-, [1,0]-, and [0,0,0]-rhodacyanines, were synthesized and their in vitro antimalarial activities against Plasmodium falciparum K1 (chloroquine-resistant strain) as well as their in vivo activities against P. berghei in mice were determined. The novel [0,0,0]-rhodacynines, 3e and 3h, possessing a benzothiazole moiety, were shown to have highly promising antimalarial activities in vivo. Moreover, the [0,0,0]-rhodacyanines were found to be orally bioavailable.

Animals↗
PubMed2006

Convergent total synthesis of (+)-mycalamide A.

The details of a convergent total synthesis of (+)-mycalamide A are described. Yb(OTf)3-TMSCl-catalyzed cross-aldol reaction conditions are used to synthesize the right segment of mycalamide A. In this reaction, an acid-sensitive aldehyde reacts with methyl trimethylsilyl dimethylketene acetal without epimerization to provide the desired aldol adduct. Additionally, a tetrahydropyran ring, which is the left segment of mycalamide A, is prepared using a novel one-pot delta-lactone formation methodology. Both segments are constructed from a common starting material, d-mannitol. These segments are then coupled in the presence of BuLi, and the functional groups are transformed to complete the synthesis of (+)-mycalamide A.

Aldehydes↗
PubMed2006

Synthesis and antimalarial efficacy of aza-fused rhodacyanines in vitro and in the P. berghei mouse model.

Several aza-fused rhodacyanines were synthesized and assessed for their in vitro and in vivo antimalarial activities against Plasmodium falciparum K1 and P. berghei. All synthetic compounds showed strong selective antimalarial in vitro activity. Class II azarhodacyanines, 3, consisting of four heterocyclic units, were found to display good parasitemia suppression and low acute toxicity in vivo. Among them, 3c appeared to be the most effective at a dose of 20-25 mg kg(-1) day(-1) (ip).

Animals↗
PubMed2006

Total synthesis of (+)-mycalamide A.

A convergent total synthesis of (+)-mycalamide A is described. A Yb(OTf)3-TMSCl catalytic system is used to synthesize a trioxadecalin ring system, which contains the right segment of mycalamide A. In addition, a tetrahydropyran ring, which is the left segment, is constructed with use of a novel one-pot delta-lactonization protocol. Both segments are prepared from a common starting material, d-mannitol. These segments are then coupled and the functional groups are transformed to synthesize (+)-mycalamide A.

Animals↗
PubMed2006

Syntheses of biologically active natural products and leading compounds for new pharmaceuticals employing effective construction of a polycyclic skeleton.

Cascade reactions are useful methods for the construction of polycyclic skeletons, which are important cores for biological activities. A variety of cascade reactions carried out under multiple reaction conditions, such as pericyclic, polar, radical, and transition metal-catalyzed reaction conditions, have been investigated. Culmorin, pentalenene, pentalenic acid, deoxypentalenic acid, longiborneol, cedrandiol, 8,14-cedranoxide, atisirene, atisine, and estrane-type steroids were synthesized via the intramolecular double Michael reaction. Aza double Michael reaction was applied to the syntheses of tylophorine, epilupinine, tacamonine, and paroxetine. Furthermore, sequential Michael and aldol reactions were performed in both intramolecular and intermolecular manners, leading to the formation of polycyclic compounds fused to a four-membered ring. Synthesis of paesslerin A utilizing a multicomponent cascade reaction revealed an error in the proposed structure. Unique cascade reactions carried out under radical and transition metal-catalyzed reaction conditions were also investigated. With the combination of several cascade reactions, serofendic acids and methyl 7beta-hydroxykaurenoate, both of which have neuroprotective activity, were synthesized in a selective manner.

Alkaloids↗
PubMed2005

Total synthesis of serofendic acids A and B employing tin-free homoallyl-homoallyl radical rearrangement.

Total syntheses of serofendic acids A (1a) and B (1b) are described. The key strategic element of the approach involves the novel tin-free homoallyl-homoallyl radical rearrangement of 5 for the construction of bicyclo[2.2.2]octane ring system 4. In addition, the conversion of methyl atisirenoate 2 to serofendic acids A (1a) and B (1b) was achieved on the basis of the Michael reaction of sodium thiomethoxide.[reaction: see text]

Catalysis↗
PubMed2005

Convenient synthesis of substituted piperidinones from alpha,beta-unsaturated amides: formal synthesis of deplancheine, tacamonine, and paroxetine.

[reaction: see text] An intermolecular aza-double Michael reaction leading to functionalized piperidin-2-ones from simple starting materials has been developed. The method allows alpha,beta-unsaturated amides to be used as a synthon of the piperidine nucleus. In addition, the utility of this methodology is demonstrated by its application to a formal synthesis of the indolo[2,3-a]quinolizidine alkaloids, (+/-)-deplancheine, (+/-)-tacamonine, and the antidepressant paroxetine.

Amides↗
PubMed2005

A practical catalytic method for preparing highly substituted cyclobutanes and cyclobutenes.

Tf2NH, an organic acid, efficiently catalyzes (2 + 2) cycloaddition reactions of silyl enol ethers with acrylates or propiolate. The process affords highly substituted cyclobutanes in high yield with high stereoselectivity under practical and environmentally benign conditions. Application for the formation of terpene skeletons and multigram synthesis of four-membered carbocycles were demonstrated.

Catalysis↗
PubMed2005

Synthesis and evaluation of beta-carbolinium cations as new antimalarial agents based on pi-delocalized lipophilic cation (DLC) hypothesis.

Several beta-carbolines including naturally occurring substances and their corresponding cationic derivatives were synthesized and evaluated for antimalarial (antiplasmodial) activity in vitro and in vivo. A tetracyclic carbolinium salt was elucidated for antileishmanial and antitrypanosomal activities in vitro as well as antiplasmodial activity. Quarternary carbolinium cations showed much higher potencies in vitro than electronically neutral beta-carbolines and a good correlation was observed between pi-delocalized lipophilic cationic (DLC) structure and antimalarial efficacy. beta-Carbolinium compounds exhibit medium suppressive activity in vivo against rodent malaria.

Animals↗
PubMed2004

Palladium-catalysed cascade ring expansion reaction of cyclobutanols that have a propargylic moiety with nucleophiles.

Cascade ring rearrangement of four-membered ring systems containing various propargylic components by a palladium catalyst is described. The reactions of cyclobutanols that have a propargylic carbonate moiety with phenols as nucleophiles produce phenoxy-induced cyclopentanones in high yields. The reactions proceed in a regio- and diastereoselective manner to afford the substituted cyclopentanones with high selectivities. Imides also act as nucleophiles to produce the imidyl-induced products. Propargylic bromide successfully reacts with sodium alkoxides to produce the corresponding products in good yields.

Journal Article↗
PubMed2004

Novel methodologies for the synthesis of cyclic carbonates.

Cyclic carbonates are valuable compounds that have applications in a variety of chemical fields. Methodologies for the synthesis of cyclic carbonates are well investigated in recent years, and the most successful and popular procedure is the utilization of CO(2). This paper presents recent progress in the synthesis of cyclic carbonates by a CO(2)-fixation process, which involves novel palladium-catalyzed CO(2)-recycling reactions.

Journal Article↗
PubMed2004

Palladium-catalyzed ring expansion reaction of (Z)-1-(1,3-butadienyl)cyclobutanols with aryl iodides. stereospecific synthesis of (Z)-2-(3-aryl-1-propenyl)cyclopentanones.

[reaction: see text] A novel type of cascade ring expansion process has been developed by the palladium-catalyzed reaction of (Z)-1-(1,3-butadienyl)cyclobutanols with aryl iodides. The reaction proceeds in a stereospecific manner to produce (Z)-2-(3-aryl-1-propenyl)cyclopentanones. It has also been found that regioselective alpha-arylation of alkenyl cyclopentanones proceeds to afford the alpha-arylated cyclopentanones.

Butanols↗
PubMed2004

Pi-delocalized beta-carbolinium cations as potential antimalarials.

Several beta-carboline compounds including natural products and their corresponding salts were synthesized and evaluated for antimalarial activity and cytotoxicity levels. Quaternary carbolinium cations showed much higher potencies than neutral beta-carbolines and a good correlation was observed between pi-delocalized lipophilic cationic structure and antimalarial efficacy.

Animals↗
PubMed2004

Palladium-catalyzed carbon dioxide elimination-fixation reaction of 4-methoxycarbonyloxy-2-buten-1-ols.

A new type of palladium-catalyzed CO(2) recycling reaction using allylic carbonates is described. Reaction of trans-4-methoxycarbonyloxy-2-buten-1-ols in the presence of a palladium catalyst produces cyclic carbonates having a vinyl group via a CO(2) elimination-fixation process. A variety of allylic carbonates participate in the reaction giving cyclic carbonates with high efficiencies. Stereoselective construction of trans-cyclic carbonates is achieved by using nonsymmetric substrates. An enantiospecific reaction proceeds to give chiral cyclic carbonate when a chiral methyl-substituted substrate is subjected to the reaction conditions.

Journal Article↗
PubMed2004

Rapid assembly of polycyclic substances by a multicomponent cascade (4 + 2)-(2 + 2) cycloadditions: total synthesis of the proposed structure of paesslerin A.

A versatile method for stereoselective formation of multisubstituted bicyclo[4.2.0]octane framework has been developed by means of catalytic (4 + 2)-(2 + 2) cycloaddition reactions. Its application to the synthesis of a substance reported to be the cytotoxic sesquiterpene, paesslerin A, is described, and it has been made clear that a revision of the structure of natural paesslerin A is required.

Bridged-Ring Compounds↗
PubMed2004

Catalytic (2 + 2)-cycloaddition reactions of silyl enol ethers. A convenient and stereoselective method for cyclobutane ring formation.

An efficient catalytic (2 + 2)-cycloaddition reaction leading to the formation of cyclobutane rings has been devised. The process transforms silyl enol ethers and alpha,beta-unsaturated esters into polysubstituted cyclobutanes with a high degree of trans-stereoselectivity. Both the rate and stereoselectivity of the process can be controlled by the choice of the ester group and silyl substituents. The results of stereochemical studies show that the cycloaddition step in this reaction proceeds in a nonstereospecific manner and, thus, by a pathway involving sequential nucleophilic additions via a short-lived zwitterionic intermediate.

Journal Article↗