HETEROCYCLES

■ Contents

■ Pyrazole Chemistry in Crop Protection

Clemens Lamberth

*Chemistry, Crop Protection Research, Syngenta AG, Schwarzwaldallee 215, CH-4058 Basel, Switzerland

Abstract

An overview is given of the significance of pyrazole derivatives in crop protection chemistry. The main herbicidally, fungicidally and insecticidally active pyrazole classes are presented, together with their synthetic routes, their modes-of-action and their biological efficacies. Indazoles and other bicyclic pyrazole derivatives are also covered.

■ The Nicotinic Acid-p-Aminophenylalanine-Hydroxybenzoic Acid Triads Induce Apoptosis in Human Leukemia U937 Cells

Mika Yamaguchi, Ryota Saito, Keiichiro Utsumi, Akira Ochiai, Norimichi Kawashima, Yoshikazu Tokuoka, and Akira Katoh*

*Department of Materials and Life Science, Faculty of Science and Technology, Seikei University, Musashino-shi, Tokyo 180-8633, Japan

Abstract

The nicotinic acid-p-aminophenylalanine-hydroxybenzoic acid triads were newly synthesized from p-aminophenylalanine methyl ester via 4 steps, and they induced apoptosis in human leukemia U937 cells. The number of hydroxyl group on benzoic acid apparently affected upon the apoptosis-inducing activity.

■ Microwave Mediated Synthesis of 3,4,4a,11a-Tetrahydro-5-phenyl/5-(4’-substituted phenyl)-2H-indeno[1,2-b]pyrano[3,2-e]pyran-6(5H)-ones

Som N. Dhawan, Mamta Sharma, Sunita Bajaj, Kusum Sharma, and Somesh Sharma*

*Department of Chemistry, Kurukshetra University, Kurukshetra-132119, Haryana, India

Abstract

Synthesis of 3,4,4a,11a-tetrahydro-5-phenyl/5-(4’-substituted phenyl)-2H-indeno[1,2-b]pyrano[3,2-e]pyran-6(5H)-ones have been reported under microwave conditions. The substrates for this being 2-benzylideneindane-1,3-dione (1) and 3,4-dihydro-2H-pyran (2); the product formation is governed by inverse Diels-Alder reaction conditions.

■ Reaction of 3-Methylenedihydro-(3H)furan-2-one with Diazoalkanes. Syntheses and Crystal Structures of Spiranic Cyclopropyl Compounds

Christophe Roussel, Kabula Ciamala,* Joël Vebrel, Michael Knorr, and Marek M. Kubicki

*Institute of UTINAM UMR CNRS 6213, Faculty of Science and Technology, University of Franche-Comté, 16 Route de Gray, F-25030 Besançon, France

Abstract

The [3+2] cycloaddition of diphenyldiazomethane (2) (1,3-dipole) with 3-methylenedihydro-(3H)furan-2-one (5) as dipolarophile leads to the spiranic cyclopropyl derivative 1,1-diphenyl-4-oxo-5-oxaspiro[2.4]heptane (8b). Compound (8b) originates from an initially formed Δ¹-pyrazoline intermediate (7’) and subsequent rearrangement after N2 extrusion. The addition of hydroquinone to the reaction medium during the synthesis has an significant effect on the [3+2] cycloaddition yield and leads to isolation of the adduct (8a), in which hydroquinone bridges two 1,1-diphenyl-4-oxo-5-oxaspiro[2.4]heptane units through hydrogen bonds. The molecular structures of (8a,b) have been ascertained by X-Ray crystallography. In contrast, the [3+2] cycloaddition of ethyl diazoacetate (6) with the dipolarophile (5) leads to the spiranic Δ²-pyrazoline compound 3’-ethoxycarbonylspiro-Δ²-pyrazolino[5’:3]dihydro-(3H)furan-2-one (10) via a prototropic rearrangement (hydrogen shift) of an initially formed Δ¹-pyrazoline intermediate (9).

■ On the Photoreaction of Some 1,2,4-Oxadiazoles in the Presence of 2,3-Dimethyl-2-butene. Synthesis of N-Imidoylaziridines

Antonio Palumbo Piccionello, Ivana Pibiri, Andrea Pace, Rosa Angela Raccuglia, Silvestre Buscemi, Nicolò Vivona,* and Gianluca Giorgi

*Dipartimento di Chimica Organica “E. Paterno”, Universita degli Studi di Palermo, Viale delle Scienze-Parco d’Orleans II, I-90128, Palermo, taly

Abstract

The photochemistry of some 3,5-disubstituted 1,2,4-oxadiazoles in the presence of 2,3-dimethyl-2-butene has been investigated. The irradiation in acetonitrile yielded differently substituted N-imidoyl-aziridines through an aziridination reaction involving an acyliminonitrene intermediate. Pyrolysis of N-imidoyl-aziridines produced the corresponding N-allylamidines through a ring opening process.

■ First Total Synthesis of (±)-Flustraminol B

Oscar R. Suárez-Castillo,* Maricruz Sánchez-Zavala, Myriam Meléndez-Rodríguez, Eliazar Aquino-Torres, Martha S. Morales-Ríos, and Pedro Joseph-Nathan

*Centro de Investigaciones Químicas, Universidad A. del Estado de Hidalgo, Apartado 1-328, Pachuca, Hidalgo, 42001, Mexico

Abstract

A first route for the synthesis of a 6-brominated marine alkaloid, flustraminol B (1), is reported using 2,6-dibromoindole (3b) as a key starting material. Bromine atoms were introduced regioselectively to 2b using NBS. The crucial selective reductive cyclization of the corresponding 6-brominated-2,3-dioxindole (7b) was successfully controlled using Red-Al^® in toluene, leading to 6-brominated pyrroloindole (8), which by selective N-methylation gave flustraminol B (1).

■ Aromatic Electrophilic Substitutions on Vindoline

Álmos Gorka-Kereskényi, Lajos Szabó, László Hazai, Miklós Lengyel, Csaba Szántay, Jr., Zsuzsanna Sánta, György Kalaus, and Csaba Szántay*

*Institute for Organic Chemistry, Budapest University of Technology and Economics, H-1111 Budapest, Gellért tér 4, Hungary

Abstract

Aromatic electrophilic substitution reactions of the monomer alkaloid vindoline resulted in new derivatives substituted on ring A. Halogene-, nitro-, amino- and acylamino derivatives of vindoline were prepared.

■ Bioactive Constituents from Chinese Natural Medicines. XXV. New Flavonol Bisdesmosides, Sarmenosides I, II, III, and IV, with Hepatoprotective Activity from Sedum sarmentosum (Crassulaceae)

Yi Zhang, Toshio Morikawa, Seikou Nakamura, Kiyofumi Ninomiya, Hisashi Matsuda, Osamu Muraoka, and Masayuki Yoshikawa*

*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan

Abstract

Four new flavonol bisdesmosides, sarmenosides I, II, III, and IV, were isolated from the whole plant of Sedum sarmentosum (Crassulaceae). Their structures were elucidated on the basis of chemical and physicochemical evidence. Among them, sarmenoside III was found to show potent hepatoprotective effect (IC₅₀ = 4.4 μM) on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes.

■ Synthesis, Characterization, and Biological Activities of New Benzofuran Derivatives

Kifah S. M. Salih, Mikdad T. Ayoub, Haythem A. Saadeh, Najim A. Al-Masoudi, and Mohammad S. Mubarak*

*Chemistry Department, Faculty of Science, University of Jordan, Amman 11942, Jordan

Abstract

A number of new benzofuran derivatives, ethyl 3-[(alkylamino)methyl]-6-methoxy-1-benzofuran-2-carboxylates (5a-i), were obtained via the reaction between ethyl 3-(bromomethyl)-6-methoxy-1-benzofuran-2-carboxylate (3) and amines or amino acid ethyl esters. In addition, 1,4-bis[(ethyl 6-methoxy-1-benzofuran-3-yl-2-carboxylate)-methyl]piperazine (9), (2E)-N,N’-diethyl-N,N’-bis[(6-methoxy-1-benzofuran-3-yl-2-carboxylate)-methyl]but-2-ene-1,4-diamine (10) and 1,2-bis[(ethyl 6-methoxy-1-benzofuran-3-yl-2-carboxylate)methyl]-1,2-dimethylhydrazine (11) were also obtained from the reaction of 3 with diamines. Their in vitro anti-HIV-1 (strain IIIB) and HIV-2 (strain ROD) activities of the synthesized compounds in human T-lymphocyte were tested; ethyl 3-bromomethyl-6-methoxycoumarlate displayed an ability to inhibit HIV-1 and HIV-2 replication in cell culture at non-toxic concentrations.

■ Microwave-Assisted Efficient Synthesis of Polymethoxyacetophenones and Natural Polymethoxyflavones, and Their Inhibitory Effects on Melanogenesis

Masao Tsukayama,* Eiji Kusunoki, Mohammad M. Hossain, Yasuhiko Kawamura, and Shinji Hayashi

*Department of Chemical Science and Technology, Faculty of Engineering, University of Tokushima, Minamijosanjima-cho, Tokushima 770-8506, Japan

Abstract

Microwave-assisted Friedel-Crafts acetylation of polymethoxybenzenes with acetic anhydride in the presence of In(CF₃SO₃)₃ under solvent-free conditions was achieved rapidly to give polymethoxyacetophenones in high yields. Microwave-assisted benzoylation of 2’-hydroxypolymethoxyacetophenones with polymethoxybenzoyl chlorides, followed by the rearrangement of the resulting benzoates and the final formation of natural polymethoxyflavones was achieved rapidly and efficiently. The polymethoxyflavones showed inhibitory effects on melanogenesis in human melanoma cells.

■ Eco-Friendly Synthesis of Novel Lariat Ethers via Mannich Reaction under Solventless Conditions

Hashem Sharghi* and Reza Khalifeh

*Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran

Abstract

An expeditious solventless synthesis of novel lariat ethers using calcium oxide (CaO) via Mannich reaction are herein described. This methodology eliminates the use of excess of solvent during the course of reaction. The reaction time is brought down from hours to minutes (20-30 minutes) along with yield enhancement. The CaO powder can be reused up to three times after simple washing with acetone.

■ One-Pot Heterocondensation for Benzoxazinone Derivatives Using Sodium Perborate as Catalyst

Mazaahir Kidwai,* Priya, and Kavita Singhal

*Green Chemistry Research Laboratory, Department of Chemistry, University of Delhi, Delhi-110 007, India

Abstract

An efficient synthesis of series of benzoxazinones, employing sodium perborate tetrahydrate (SPB) as a condensing agent is described. SPB in water and formic acid system is proved as a selective catalyst of hydration for cyanides. The rate enhancement and high yield is attributed to the coupling of suitable catalyst with this solvent system. This methodology eliminates the number of steps during the reaction.

■ Studies toward the Synthesis of Toddaquinoline by Intramolecular Cyclization

Georgeta Serban,* Yasumi Shigeta, Hiromi Nishioka, Hitoshi Abe, Yasuo Takeuchi, and Takashi Harayama*

*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

-In connection with studies on the total synthesis of toddaquinoline (1), the synthesis of [1,3]dioxolo-[4’,5’:4,5]benzo[h]quinoline (1a), which is the tetracyclic core of 1, was investigated. Intramolecular benzene-pyridine coupling reactions of the monobromide (9) and dibromide (10), using a Pd reagent and Cu reagent, were evaluated to produce 1a in poor to moderate yields.