HETEROCYCLES

■ Contents

■ Development of Samarium Diiodide-Promoted Reductive Carbon-Nitrogen Bond Cleavage Reaction of α-Amino Carbonyl Compounds: Application to the Synthesis of Biologically Active Alkaloids

Toshio Honda*

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Samarium diiodide (SmI2) is a mild and selective one electron transfer reagent, and has become an important tool for developing a variety of useful and unique transformations. SmI2 has been utilized in a wide range of synthetic transformations ranging from interconversion of functional groups to carbon-carbon bond forming reactions. Among the various reactions developed for SmI2, we focused our attention on its use for fragmentation reactions. We have already established a regioselective carbon-carbon bond cleavage reaction of γ-halo carbonyl compounds, and its utilization in the synthesis of various types of biologically active natural products. However, a SmI2-promoted reductive carbon-nitrogen bond cleavage reaction has received relatively little attention. In this review article, we would like to describe a general carbon-nitrogen bond cleavage reaction of α-amino carbonyl compounds and the utilization of this methodology in the synthesis of a number of bioactive alkaloids, since this reaction proceeds in relatively high yield under mild reaction conditions.

■ Facile Synthesis of 3-(Succinimid-3-yl)-2-oxo-2,3-dihydroimidazo[1,2-a]pyridine Derivatives by Sequential Intra- and Intermolecular Michael Reactions between 2-Aminopyridines and Maleimides

Tetsuro Shimo,* Tomoko Itoh, Yasutaka Araki, Tetsuo Iwanaga, Teruo Shinmyozu, and Kenichi Somekawa

*Department of Applied Chemistry and Chemical Engineering, Faculty of Engineering, Kagoshima University, Korimoto, Kagoshima 890, Japan

Abstract

3-(Succinimid-3-yl)-2-oxo-2,3-dihydroimidazo[1,2-a]pyridine derivatives (3 and 4) were prepared through a one-pot reaction from 2-aminopyridines (1) by acylation with maleimides (2) and followed by an intramolecular Michael addition, and a subsequent second Michael addition with another molecule of 2. The diastereomeric configurations of the products were confirmed by X-ray crystal analyses. The reaction mechanism of the accumulated three types of additions between 1 and two equimolar amounts of 2 was calculated using MOPAC-PM6 molecular simulations and the competing addition reactions as hard and soft reactions were explained by HSAB theory.

■ Structure-Activity Relationships on Senescence-Promoting Effect of Arabidopsides from Arabidopsis thaliana

Haruyuki Nakajyo, Yosuke Hisamatsu, Nobuharu Goto, Kosumi Yamada, Koji Hasegawa, and Hideyuki Shigemori*

*Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305, Japan

Abstract

Arabidopsides A-D and F isolated from Arabidopsis thaliana are rare oxylipins containing 12-oxophytodienoic acid (OPDA) and/or dinor-oxophytodienoic acid (dn-OPDA) which are known as precursors of jasmonic acid (JA) and methyl jasmonate (MeJA). The senescence-promoting effect of these arabidopsides A-D and F were examined by an oat (Avena sativa) leaf assay. Arabidopsides C and D, digalactosyldiacylglycerides containing OPDA and/or dn-OPDA, are more effective on leaf senescence than arabidopsides A, B, and F, monogalactosyldiacylglycerides containing OPDA and/or dn-OPDA. The effect of arabidopsides C and D is the almost same as that of JA, MeJA, and OPDA, which are well known to be senescence promoters. These results suggest that arabidopsides A-D and F play important roles in leaf senescence.

■ Lewis Acid Promoted Diastereoselective Mannich Reaction of β-Lactam-Tethered Aldimines with 1-Methoxy-1-trimethylsilyloxy-2,2-dimethylethene

Katarina Vazdar, Davor Margetić, and Ivan Habuš*

*Ruđer Bošković Institute, Bijenička c. 54, P.O.B. 180, HR-10002 Zagreb, Croatia

Abstract

Lewis acid (ZnI2) – promoted Mannich reaction of azetidin-2-one – tethered aldimines 3a-r with silylenol ether 4 in toluene at –20 °C afforded a diastereomeric mixture of β-amino acid esters 5a-r/6a-r. The effect of the amount of zinc(II) iodide, equimolar (100 mol%) and catalytic (20 mol%), on the chemical yield and the product stereoisomeric ratio was studied. The diastereoselective Mannich reaction of imine 3a with silylenol ether 4 at low temperature (–20 °C) in toluene under equimolar zinc(II) iodide catalysis provided the best chemical yield – 99% combined with the highest diastereoselectivity of β-amino acid esters 5a/6a – 85:15%. Furthermore, the influence of various groups on azetidin-2-one – tethered imines 3a-r (R1 = phenyl, ferrocenyl; R2 = alkyl, aryl, ferrocenyl) has been applied in the Mannich reaction leading to the formation of two stereoisomers of β-amino acid esters 5a-r/6a-r with diastereomeric ratio varying from 92:8 to 59:41%.

■ Synthesis of Novel 5-(Pyrimidin-5-yl)-1,2,4-oxadiazole Derivatives via a Three-Component Cycloaddition and Subsequent Oxidative Dehydrogenation

Tong-Hui Huang, Hai-Yang Tu,* Ming Liu, and Ai-Dong Zhang*

*Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China

Abstract

A new and efficient strategy has been developed for the synthesis of novel 5-(pyrimidin-5-yl)-1,2,4-oxadiazoles with a wide diversity in substituents via Biginelli cycloaddition and subsequent oxidative dehydrogenation.

■ An Efficient Synthesis of 3-Substituted 3H-Isobenzofuran-1-ylidenamines by the Reaction of 2-Cyanobenzaldehydes with Organolithiums and Their Conversion into Isobenzofuran-1(3H)-ones

Kazuhiro Kobayashi,* Kota Matsumoto, and Hisatoshi Konishi

*Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

A new and efficient synthesis of 3-substituted 3H-isobenzofuran-1-ylidenamines by the reaction of 2-cyanobenzaldehydes with nucleophiles, such as organolithiums or lithium enolates of t-butyl acetate and N,N-dimethylacetamide, is reported. Some of these products were converted into the corresponding 3-substituted isobenzofuran-1(3H)-ones (phthalides) upon treatment with hydrochloric acid in satisfactory yields.

■ An Experimental Study of Special Leaving Group Behavior in the Reaction of Arylidenebarbituric Acids with Carbon Nucleophiles

Mohammad A. Bigdeli, Enayatollah Sheikhhosseini,* Azizollah Habibi, and Saeed Balalaie

*Faculty of Chemistry, Tarbiat Moallem Uinversity, no. 49, Mofateh Ave. Tehran, Iran

Abstract

The reaction of benzylidenebarbituric acid and 1,3-dimethylbenzylidenebarbituric acid with malononitrile as well as with dimedone in piperidine is investigated. In reaction with malononitrile, substituted pyridine-3,5-dicarbonitriles are obtained, while with dimedone, xanthenes and/or 6-hydroxy-5-((2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)(aryl)methyl)-1,3-dimethyl pyrimidine-2,4(1H,3H)-dione derivatives are isolated.

■ Heck Reactions in 2,6-Diaryl-3,5-dibromo-4-pyrones in the Presence of N,N’-Dibutylbenzimidazolium Bromide

Zarrin Ghasemi, Vahideh Nazari-Belvirdi, Maryam Allahvirdinasab, and Aziz Shahrisa*

*Department of Organic and Bioorganic Chemistry, Faculty of Chemistry, University of Tabriz, 51664, Tabriz, Iran

Abstract

Synthesis of two 2,6-diaryl-3,5-dibromo-4-pyrone derivatives is described, by using of NBS/DMF bromination of related 2,6-diaryl-4-pyrones. PdCl2 catalyzed Heck coupling reactions of these dibromides, with emphasis on the use of N,N′-dibutylbenzimidazol-2-ylidene as ligand, resulted in the formation of two class of mono- and di-vinylated products.

■ Synthesis of Fluoroquinolone-di- and tri-(N-methylpyrrole) Conjugates

Ichiro Suzuki,* Mayuko Takahashi, and Kei Takeda

*Divison of Medicinal Chemisry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan

Abstract

Some FLQs, such as lomefloxacin and fleroxacin, having two fluorine atoms are known to generate an arylcarbene under photoirradiation conditions leading to DNA damage. We synthesized some conjugates between FLQs and di- and tri-(N-methylpyrrole) that are known as a DNA minor groove binder.

■ Two New Flavonol Glycosides from Sedum aizoon L.

Wei Lin Li,* Qiu Yan Luo, Li qiang Wu, and Lei Xiao

*Department of Medicinal Chemistry, Pharmacy College, Xinxiang Medical University, Xinxiang 453003, China

Abstract

Two new flavonol glycosides, Sedacins C (1) and D (2), and two known compounds (3-4), have been isolated from the whole plant of Sedum aizoon L. Their structures have been established as 6''-O-(E)-feruloylquercetin (1) and 6''-O-(E)-feruloylisorhamnetin (2) by means of spectroscopic analysis and chemical methods.

■ The First Total Syntheses of (+)-Hostmanin A and (+)-Methyllinderatin

Junko Kitao, Naoko Kitamura, Nozomi Kumo, Kenji Arimitsu, Hiroki Iwasaki, Minoru Ozeki, Ai Kurume, and Masayuki Yamashita*

*Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi, Yamashina, Kyoto, Japan

Abstract

The first total syntheses of (+)-hostmanin A (1) and (+)-methyllinderatin (3) were achieved in four steps from a known compound, 1-{2,6-dihydroxy-4-methoxy-3-[(1R,6R)-3-methyl-6-(1-methylethyl)-2-cyclohexen-1-yl]phenyl}ethanone (6). The absolute configuration of (+)-methyllinderatin (3) was determined. Furthermore, (+)-hostmanin A (1), which was isolated as an inseparable mixture of hostmanin A and B, was synthesized as a sole component.

■ A Convenient Method for Synthesis of 5-Chloro-2-aryloxazole-4-carbaldehyde with Vilsmeier Reagent

Can Jin, Jun Chen, and Weike Su*

*Key Laboratory of Pharmaceutical Engineering of Ministry of Educations, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China

Abstract

A convenient method for synthesis of 5-chloro-2-aryloxazole-4-carbaldehyde 3 in moderate to good yields had been developed via the Vilsmeier reaction of readily available N-arylglycine 2 at 100 oC, provided a novel route for the construction of nitrogen heterocycles. A series of these compounds were synthesized by this method and optimization of conditions was performed.

■ Palladium-Catalyzed Cyanation of Aryl Bromides Using Phosphine-Free Pyridylhydrazone Ligands

Takashi Mino,* Tomoko Koizumi, Masanori Shibuya, Kiminori Hirai, Masami Sakamoto, and Tsutomu Fujita

*Faculty of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

Palladium-catalyzed cyanation of aryl bromides with potassium hexacyanoferrate(II) trihydrate, K4[Fe(CN)6]·3H2O as the cyanide source gave benzonitrile derivatives using a catalytic amount of Pd(OCOCF3)2 in DMF at 110 °C with phosphine-free pyridyl-hydrazone ligand 2c in good yields.

■ A Simple and Efficient Method for Synthesis of Benzothiazepine Derivatives

Saori Itabashi, Rong Lu, and Tetsuo Miyakoshi*

*Department of Applied Chemistry, School of Science and Technology, Meiji University, 1-1-1 Higashi-mita, Tama-ku, Kawasaki-shi, 214-8571, Japan

Abstract

A series of 1,5-benzothiazepines were synthesized using disulfides and α,β-unsaturated carbonyl or nitrile compounds as reaction substrates. After reductive cleavage of the S-S bond of disulfides, the resulting thiols were reacted with α,β-unsaturated carbonyl or nitrile compounds to generated seven-membered heterocyclic compounds. In the presence of ammonium thioglycolate, the Michael reaction occurred between disulfides (1) and 4-methyl-3-penten-2-one to give 2,2,4-trymethyl-3H-1,5-benzothiazepine derivatives in good yields. When ethyl acrylate or acrylonitrile was used as the Michael acceptor, 90-99% of (2-amino-phenylsulfanyl)propionitriles (3) and/or 92-99% of (2-amino-phenylsulfanyl)propionic acid ethyl esters (4) were produced. Subsequently, the 1,5-benzothiazepine compounds 5 and 6 were obtained due to the cyclization reaction.