Tatsunori Iwamura

The Chalcogeno-Baylis-Hillman Reaction : A New Preparation of Allylic Alcohols from Aldehydes and Electron-deficient Alkenes.

Abstract The chalcogeno-Baylis-Hillman reaction catalyzed by sulfides and selenides, the group 16 element compounds, in the presence of Lewis acids was developed. The reactions proceeded smoothly by the use of 1 equiv of TiCl4 to give the coupling products in moderate to good yields. Bis-chalcogenides and related compounds were investigated as a catalyst, and 1,5-diselenocyclooctane gave the best result owing to stabilization of a cationic intermediate by the transannular interaction.

Reexamination of Products and the Reaction Mechanism of the Chalcogeno-Baylis–Hillman Reaction: Chalcogenide–TiCl4-mediated Reactions of Electron-Deficient Alkenes with Aldehydes

Abstract Reactions of p -nitrobenzaldehyde ( 4 ) with methyl vinyl ketone ( 5 ) were conducted in the presence of TiCl 4 and dimethyl sulfide ( 3 ) or selenopyranone 6 . When the raw product was purified by column chromatography on silica gel, α-chloromethyl aldol 8 was obtained as a mixture of diastereoisomers 8a and 8b . In contrast, purification of the raw product by preparative TLC on silica gel gave α-methylene aldol 7 . The mechanism for the formation of α-chloromethyl aldol 8 and diasteroselection for the syn -isomer 8a and anti -isomer 8b are discussed.

Synthesis and antimalarial activity of calothrixins A and B, and their N-alkyl derivatives.

We synthesized calothrixin B using our developed biomimetic method and derived N-alkyl-calothrixins A and B. The in vitro antimalarial activity of the calothrixin derivatives, including calothrixins A and B, against the Plasmodium falciparum FCR-3 strain was evaluated. All test compounds exhibited antimalarial activity over a concentration range of 6.4×10(-6)-1.2×10(-7) M.

REACTIONS OF ALKYNYLSELENONIUM SALTS WITH SODIUM BENZENESULFINATE

Abstract Alkynylselenonium salts 2 and 5 were synthesized and treated with benzenesulfinic acid or its sodium salt in an alcohol. The reactions with sodium benzenesulfinate gave (Z)-β-alkoxyvinylsulfones 6 as main products, while the reactions with benzenesulfinic acid afforded the β-sulfonylvinylselenonium salts 11 and 12 in good yields.

Effects of MDMA on Extracellular Dopamine and Serotonin Levels in Mice Lacking Dopamine and/or Serotonin Transporters

3,4-Methylendioxymethamphetamine (MDMA) has both stimulatory and hallucinogenic properties which make its psychoactive effects unique and different from those of typical psychostimulant and hallucinogenic agents. The present study investigated the effects of MDMA on extracellular dopamine (DAex) and serotonin (5-HTex) levels in the striatum and prefrontal cortex (PFC) using in vivo microdialysis techniques in mice lacking DA transporters (DAT) and/or 5-HT transporters (SERT). subcutaneous injection of MDMA (3, 10 mg/kg) significantly increased striatal DAex in wild-type mice, SERT knockout mice, and DAT knockout mice, but not in DAT/SERT double-knockout mice. The MDMA-induced increase in striatal DAex in SERT knockout mice was significantly less than in wildtype mice. In the PFC, MDMA dose-dependently increased DAex levels in wildtype, DAT knockout, SERT knockout and DAT/SERT double-knockout mice to a similar extent. In contrast, MDMA markedly increased 5-HTex in wildtype and DAT knockout mice and slightly increased 5-HTex in SERT-KO and DAT/SERT double-knockout mice. The results confirm that MDMA acts at both DAT and SERT and increases DAex and 5-HTex.

Pharmacological study of dihydroetorphine in cloned μ-, δ- and κ-opioid receptors

Abstract We investigated the binding characteristics of dihydroetorphine, 7,8-dihydro-7α-[1-(R)-hydroxyl-1-methylbutyl]-6,14-endoethano-tetrahydro-oripavine, and its effect on the inhibitory system of cyclic AMP production using cloned μ-, δ- and κ-opioid receptors expressed on Chinese hamster ovary cells. The Ki values of dihydroetrophine for the μ-, δ- and κ-opioid receptor were 4.5 × 10−10, 1.8 × 10−9 and 5.7 × 10−10 M, respectively. On the hand, those of morphine were 1.9 × 10−9, 1.4 × 10−6 and 1.3 × 10−7 M, respectively. Through all of these three types of opioid receptors, dihydroetorphine inhibited forskolin (10 μM)-stimulated cyclic AMP production via pertussis toxin-sensitive G protein(s), and the inhibitory effects were antagonized by co-application with opioid receptor antagonists. The IC50 values of dihydroetorphine for the inhibition of cyclic AMP production through the μ-, δ- and κ-opioid receptors were 4.2 × 10−11, 8.6 × 10−10 and 4.3 × 10−9 M, respectively. On the other hand, those of morphine were 2.6 × 10−8, 2.6 × 10−6 and 1.9 × 10−6 M, respectively. These results indicate that dihydroetorphine, unlike morphine which preferentially binds the μ-opioid receptor, binds not only μ- but also δ- and κ-opioid receptors with high affinity and acts as a more potent agonist than morphine for all of the three types of receptors.

Neuroleptic malignant syndrome and serotonin syndrome.

This chapter is focused on drug-induced hyperthermia with special regard to use of antipsychotics and antidepressants for the treatment of schizophrenia and major depression, respectively. Neuroleptic malignant syndrome (NMS) develops during the use of neuroleptics, whereas serotonin syndrome is caused mainly by serotoninergic antidepressants. Although both syndromes show various symptoms, hyperthermia is the main clinical manifestation. In this review we describe the historical background, clinical manifestations, diagnosis, and differential diagnosis of these two syndromes based on our observations on the experimental and clinical data.

Tandem Michael-aldol reaction via 6-endo-dig cyclization of ynone-chalcogenides: synthesis of 2-unsubstituted 3-(hydroxyalkyl)chalcogenochromen-4-ones

The reactions of 1-(2-methylchalcogenophenyl)propynone with aldehydes gave 3-(hydroxyalkyl)chalcogenochromen-4-ones via the 6-endo-dig cyclization and aldol reaction. Selenochromen-4-ones were obtained in higher yields than the thiochromen-4-ones.

Dimethyl Sulfide-Boron Trihalide-Mediated Reactions of α, β-Unsaturated Ketones with Aldehydes : One-pot Synthesis of Baylis Hillman Adducts and α-Halomethyl Enones

Abstract The reactions of aldehydes with 3-buten-2-one ( 2 ) were conducted in the presence of BBr 3 ·Me 2 S or BCl 3 ·Me 2 S and then worked up with aqueous NaHCO 3 , affording the α-methylene aldol 3 , α-halomethyl aldol 4 or 6 , and α-halomethyl enones 5 or 7 , respectively. In contrast, the reactions quenched with water gave the α-halomethyl enones 5 or 7 in high yields, while the work-up with an aqueous 10% trimethylamine gave the α-methylene aldol 3 . The phenol 15 and half-acetal 16 were obtained from the reaction of p -nitrobenzaldehyde ( 1a ) with cyclohexenone ( 10 ).

Opioid receptor interaction and adenylyl cyclase inhibition of dihydroetorphine: direct comparison with etorphine

To find out the reason of weak addiction property of dihydroetorphine, we compared the affinities of dihydroetorphine to the type selective opioid receptor and inhibition effect on the adenylyl cyclase activity with those of etorphine. Dihydroetorphine and etorphine have almost the same binding affinities to all types (mu, delta, and kappa) of opioid receptors and antagonist binding sites, and have similar inhibition activities to forskolin stimulated adenylyl cyclase. However, dihydroetorphine showed significantly smaller value of DTNB-index compared with that of etorphine. This differentiation may explain partly the high analgesic with low dependence properties of dihydroetorphine.