Ring expansion of spirocyclopropanes with stabilized sulfonium ylides: highly diastereoselective synthesis of cyclobutanes.

A novel method was devised for regioselective ring expansion of Meldrum's acid-derived spirocyclopropanes to spirocyclobutanes with stabilized sulfonium ylides, affording 1,2--disubstituted 6,8-dioxaspiro[3.5]nonane-5,9-diones in up to 87% yields without the formation of any isomers. The aforementioned reaction was also applied to the barbituric acid-derived spirocyclopropane, resulting in the formation of the corresponding cyclobutanes.

8-Iodoisoquinolinone, a Conformationally Rigid Highly Reactive 2-Iodobenzamide Catalyst for the Oxidation of Alcohols by Hypervalent Iodine.

The first lactam-type 2-iodobenzamide catalysts, 8-iodoisoquinolinones 8 (IB-lactam) and 9 (MeO-IB-lactam), were developed. These catalysts have a conformationally rigid 6/6 bicyclic lactam structure and are more reactive than the previously reported catalysts 2-iodobenzamides 4 (IBamide) and 5 (MeO-IBamide) for the oxidation of alcohols. The lactam structure could form an efficient intramolecular I---O interaction, depending on the size of the lactam ring.

Boron Trifluoride-Mediated Domino Dehydration/Electrophilic Cyclization of Silylalkynols Leading to 2,3-Fused Tricyclic Benzofulvenes.

A BF-mediated domino dehydration/electrophilic cyclization of silylalkynols to form 2,3-fused tricyclic benzofulvenes was achieved. In the latter step, in situ generated BF·OH enables the electrophilic activation of alkynes. The predominant -selectivity of the reaction is also discussed.

Efficient and Environmentally Benign Oxidative Cleavage of Pyrrolidine-2-methanols to γ-Lactams Using 2-Iodobenzamide as a Catalyst and Oxone.

The oxidative cleavage reaction of pyrrolidine-2-methanols to γ-lactams has been described. In this reaction, [4-iodo-3-(isopropylcarbamoyl)phenoxy]acetic acid and powdered Oxone (2KHSO·KHSO·KSO) were employed as the catalyst and co-oxidant, respectively. The reaction is efficient and environmentally benign because it produces various lactams from readily available substrates in moderate to excellent yields using organocatalyst and inorganic non-toxic co-oxidant.

Dearomative Intramolecular Diels-Alder/Sulfur Extrusion Reaction of Thiophenes with Alkynes Using peri-Substituted Naphthalene as a Tether.

Dearomative intramolecular Diels-Alder/sulfur extrusion reaction of thiophenes with alkynes successfully afforded fluoranthenes in moderate to excellent yields. The proximity of both reactive sites fixed at the peri-position of naphthalene would play an important role in the progress of this reaction. Tri(o-tolyl)phosphine effectively suppressed the side reactions as a sulfur scavenger.

Bismuth(III)-Catalyzed Oxidative Cross-Coupling of 3-Hydroxycarbazoles with Arenols under an Oxygen Atmosphere.

A Bi(OTf)-catalyzed oxidative cross-coupling reaction of 3-hydroxycarbazoles with arenols was developed under mild conditions. Both substrates were used in a 1:1 molar ratio in the presence of a catalytic amount of Bi(OTf). The reaction was carried out under an oxygen atmosphere at 30 °C to afford -symmetric hydroxybiaryls in good yields (up to 94%) with high chemo- and regioselectivity.

Ring-Opening Cyclization of Spirocyclopropanes Using Sulfoxonium Ylides.

Ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes using dimethylsulfoxonium methylide proceeded regioselectively to produce 2,3,4,6,7,8-hexahydro-5H-1-benzopyran-5-ones in good to high yields. The reactions of cycloheptane- and cyclopentane-1,3-dione-2-spirocyclopropanes could construct [7.6]- and [5.

Protecting-Group-Free Formal Synthesis of Aspidospermidine: Ring-Opening Cyclization of Spirocyclopropane with Amine Followed by Regioselective Alkylations.

A concise formal synthesis of (±)-aspidospermidine via Stork's intermediate, which could be used as a divergent synthesis of alkaloids, was achieved by employing a ring-opening cyclization of spirocyclopropane with amine followed by a regioselective intramolecular/intermolecular alkylation sequence. Stork's intermediate was synthesized in only six steps from a simple starting material, 1,3-cyclohexanedione, and was converted into (±)-aspidospermidine. To the best of our knowledge, this synthesis of Stork's intermediate involves the least number of steps to date.

Synthesis and biological evaluation of 2-epi-jaspine B analogs as selective sphingosine kinase 1 inhibitors.

2-Epi-jaspine B is an isomer of the natural product jaspine B and shows certain selectivity for SphK1 and potent antitumor activity. Based on the crystal structure of SphK1, we transformed the structure of 2-epi-jaspine B and modified the hydrophobic side chain to obtain a series of 2-epi-jaspine B analogs. The MTT assay was used to examine the antitumor activities of these analogs.

Ring-opening cyclization of spirocyclopropanes with stabilized sulfonium ylides for the construction of a chromane skeleton.

Regioselective ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes with stabilized sulfonium ylides provided 2,3-trans-disubstituted 2,3,4,6,7,8-hexahydro-5H-1-benzopyran-5-ones in high yields without the formation of any isomers. The obtained product was readily converted into highly substituted chromane.

2-Iodo--isopropyl-5-methoxybenzamide as a highly reactive and environmentally benign catalyst for alcohol oxidation.

Several -isopropyliodobenzamides were evaluated as catalysts for the oxidation of benzhydrol to benzophenone in the presence of Oxone (2KHSO·KHSO·KSO) as a co-oxidant at room temperature. A study on the substituent effect of the benzene ring of -isopropyl-2-iodobenzamide on the oxidation revealed that its reactivity increased in the following order of substitution: 5-NO < 5-COMe, 3-OMe < 5-OAc < 5-Cl < H, 4-OMe < 5-Me < 5-OMe. The oxidation of various benzylic and aliphatic alcohols using a catalytic amount of the most reactive 5-methoxy derivative successfully resulted in moderate to excellent yields of the corresponding carbonyl compounds.

An Efficient Route to Highly Substituted Indoles via Tetrahydroindol-4(5H)-one Intermediates Produced by Ring-Opening Cyclization of Spirocyclopropanes with Amines.

An efficient route to highly substituted indoles was developed. It included regioselective functionalization of tetrahydroindol-4(5H)-ones, prepared by ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes with primary amines, and subsequent oxidation. The 6-substituted indoles were synthesized from a readily available 5-substituted cyclohexane-1,3-dione-2-spirocyclopropane.

Total Synthesis of Sphingofungin E and 4,5-Di-epi-sphingofungin E.

Total synthesis of sphingofungin E and 4,5-di-epi-sphingofungin E was achieved from an intermediate same as that of myriocin and mycestericin D via antipodal stereoselective dihydroxylations.

An Efficient Method for the Synthesis of 2',3'-Nonsubstituted Cycloalkane-1,3-dione-2-spirocyclopropanes Using (2-Bromoethyl)diphenylsulfonium Trifluoromethanesulfonate.

An efficient and practical synthesis of 2',3'-nonsubstituted cyclohexane-1,3-dione-2-spirocyclopropanes using a sulfonium salt was achieved. The reaction of 1,3-cyclohexanediones and (2-bromoethyl)diphenylsulfonium trifluoromethanesulfonate with powdered KCO in EtOAc at room temperature (r.t.

Synthetic Studies on a Pachastrissamine Sulfur Analogue: Synthesis of a 4-epi-Sulfur Analogue.

A versatile synthetic procedure for a sulfur analogue of pachastrissamine (jaspine B), which involves the tandem thiolation-cyclization of a 1,4-ditosylate to construct a tetrahydrothiophene ring, was developed. Nucleophilic amino substitution of a tetrahydrothiophene-4-sulfonate with unexpected retention of the configuration afforded the sulfur analogue of 4-epi-pachastrissamine.

Involvement of c-Myc-mediated transient receptor potential melastatin 8 expression in oxaliplatin-induced cold allodynia in mice.

Background: Oxaliplatin, a platinum-based chemotherapeutic agent, induces acute cold allodynia and dysesthesia. Cold-sensitive transient receptor potential channels (TRPM8 and TRPA1) have been implicated as candidates to mediate oxaliplatin-induced cold allodynia and hyperalgesia, but precise roles of these channels remain unclear. In this study, we investigated the role of TRPM8 in oxaliplatin-induced cold allodynia.

Practical Synthesis of Pachastrissamine (Jaspine B), 2-epi-Pachastrissamine, and the 2-epi-Pyrrolidine Analogue.

The practical syntheses of pachastrissamine (jaspine B), 2-epi-pachastrissamine, and the 2-epimer of the pyrrolidine analogue were accomplished via the stereoselective reduction of an allylketone derived from commercially available diethyl D-tartrate and the cross-metathesis of an allyltetrahydrofuran or allypyrrolidine with 1-tridecene as key steps.

Ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes with amines: rapid access to 2-substituted 4-hydroxyindole.

An efficient ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes with primary amines has been developed. The reaction proceeded at room temperature without any additives to provide 2-substituted tetrahydroindol-4-ones in good to excellent yields without the formation of the 3-substituted isomers. The obtained product was readily converted into a 2-substituted 4-hydroxyindole derivative via a synthetically useful indoline intermediate.

An efficient catalytic oxidation of p-Alkoxypenols to p-quinones using tetrabutylammonium bromide and oxone.

A catalytic oxidation of p-alkoxyphenols was developed using tetrabutylammonium bromide (TBAB) and Oxone(®). The reaction of p-alkoxyphenol (1) with a catalytic amount of TBAB in the presence of Oxone(®) as a co-oxidant in acetonitrile-water (2 : 1) gave the corresponding p-quinone (2) in excellent yield without special treatment.

Efficient synthesis of p-quinols using catalytic hypervalent iodine oxidation of 4-arylphenols with 4-iodophenoxyacetic acid and oxone.

Efficient synthesis of p-quinols (2) using catalytic hypervalent iodine oxidation of 4-arylphenols (1) with 4-iodophenoxyacetic acid (3) and Oxone was developed. Reaction of 1 with a catalytic amount of 3 in the presence of Oxone as a co-oxidant in tetrahydrofuran or 1,4-dioxane-water gave the corresponding 2 in excellent yields.

Catalytic hypervalent iodine oxidation using 4-iodophenoxyacetic acid and oxone: oxidation of p-alkoxyphenols to p-benzoquinones.

A catalytic hypervalent iodine oxidation of p-alkoxyphenols using 4-iodophenoxyacetic acid (1a) and Oxone((R)) was developed. Reaction of p-alkoxyphenol (2) with a catalytic amount of 1a in the presence of Oxone((R)) as a co-oxidant in 2,2,2-trifluoroethanol-water (1 : 2) gave the corresponding p-quinone (3) in excellent yield without special operation. The substituent effect on iodobenzene ring in the oxidation was observed; p-alkoxy is the most effective, with the series following the approximate order p-RO>p-Me, o-MeO, m-MeO>H>o-CO(2)H.

Catalytic hypervalent iodine oxidation of p-dialkoxybenzenes to p-quinones using 4-iodophenoxyacetic acid and Oxone.

A catalytic hypervalent iodine oxidation of p-dialkoxybenzenes using 4-iodophenoxyacetic acid (1) and 2KHSO5 x KHSO4 x K2SO4 (Oxone) was developed. Reaction of p-dialkoxybenzenes (2) with a catalytic amount of 1 in the presence of Oxone as a co-oxidant in 2,2,2-trifluoroethanol-water (1 : 2) gave the corresponding p-quinones (3) in excellent yields without purification. This procedure was applied to synthesis of blattellaquinone (9), the sex pheromone of the German cockroach, Blattella germanica.

Dirhodium(II)-catalyzed C-H amination reaction of (S)-3-(tert-butyldimethylsilyloxy)-2-methylpropyl carbamate: a facile preparation of optically active monoprotected 2-amino-2-methyl-1,3-propanediol.

Dirhodium(II)-catalyzed C-H amination reaction of (S)-3-(tert-butyldimethylsilyloxy)-2-methylpropyl carbamate, which was easily prepared from methyl (S)-2-methyl-3-hydroxypropanoate, proceeded more smoothly than those of their 2-(methoxycarbonyl)propyl derivative to give the corresponding oxazolidinone in excellent yield. The resulting oxazolidinone was converted efficiently into both (R)-monoprotected and (S)-monoprotected 2-amino-2-methyl-1,3-propanediols.

Enantioselective synthesis of pachastrissamine (jaspin B) using dirhodium(II)-catalyzed C-H amination and asymmetric dihydroxylation as key steps.

Enantioselective total synthesis of anhydrophytosphingosine pachastrissamine (jaspin B) was achieved using Sharpless asymmetric dihydroxylation and dirhodium(II)-catalyzed C-H amination as key steps.

Stereoselective synthesis of c3-c12 dihydropyran portion of antitumor laulimalide using copper-catalyzed oxonium ylide formation-[2,3] shift.

Copper-catalyzed oxonium ylide formation-[2,3] shift of (5S,7R)-5-allyloxy-1-diazo-8-(p-methoxybenzyloxy)-7-methyl-2-octanone (3) proceeded in tetrahydrofuran-dichloromethane (4 : 1) under reflux with an excellent stereoselectivity (97 : 3) to give (2R,6S)-2-allyl-6-[(2R)-3-(p-methoxybenzyloxy)-2-methylpropyl]-3-dihydropyranone (2) as a major isomer in 82% yield. The resultant pyranone (2) was converted to the key intermediate (1) of the Mulzer's laulimalide synthesis and its derivatives (14, 15).