HETEROCYCLES

■ Contents

■ Transition Metal-Mediated Synthesis of Oxazoles

Stefano Bresciani and Nicholas C. O. Tomkinson*

*Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow, G1 1XL, U.K.

Abstract

Among the synthetic methods for the formation of the oxazole ring, transition metal-mediated protocols are the most attractive in terms of selectivity, efficiency and mildness of reaction conditions. In this review we discuss methods for the preparation of oxazoles using transition metal complexes highlighting the key bonds being formed. This reveals critical gaps in the existing literature for the construction of this biologically significant ring system highlighting exciting opportunities for further research.

■ The Reaction of 2-((Trimethylsilyl)methyl)-2H-tetrazoles with Aldehydes and Ketones in the Presence of 1,8-Diazabicyclo[5.4.0]undec-7-ene

Hideaki Umemoto,* Takuya Onaka, Yasuyoshi Miki, Akira Nakamura, and Tomohiro Maegawa*

*Business Development Department, FUJIMOTO CHEMICALS Co., Ltd., 1-2-38 Kinrakuji-cho, Amagasaki, Japan

Abstract

2-((Trimethylsilyl)methyl)-2H-tetrazoles were treated with aldehydes and ketones in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give 2-(2-hydroxyethyl)-2H-tetrazoles. This simple procedure offers a valuable strategy for the preparation of 2-(hydroxyethyl)-2H-tetrazoles.

■ Phosphorylated Thiacalix[6]arene: Synthesis and Characterization of Host-Guest Complex of Selective Pd2+ Ion Extraction

Munkhtuya Ulzii, Kunda Uma Maheswara Rao, Manabu Yamada, and Fumio Hamada*

*Department of Applied Chemistry, Akita University, Tegata-gakuenncho 1-1, Akita 010-0852, Japan

Abstract

New phosphorylated thiacalix[6]arene was synthesized and its metal extraction ability was examined by using automotive catalyst residue solution. The new host molecule showed high affinity towards Pd2+ ion and reasonable affinity towards other metals. Then we studied the effect of concentration and time on the Pd2+ ion extraction using Pd2+ ion standard solution. In addition to this, we successfully characterized the host-guest complex formed during Pd2+ ion extraction by using Job’s method, 31P & 1H NMR, IR and elemental analysis.

■ Rhodium(I)-N-Heterocyclic Carbene-Catalyzed Addition of Sodium Tetraphenylborate to Ketones to Form Tertiary Alcohols

Beyhan Yiğit, Murat Yiğit,* and İsmail Özdemir

*Department of Chemistry, Faculty of Arts and Sciences, Adıyaman University, 02040 Adıyaman, Turkey

Abstract

Rhodium complexes ([Rh(COD)(NHC)Cl]) were synthesized by the reaction of bis(1,3-dialkylperhydrobenzimidazolin-2-ylidene) with [RhClCOD]2 in toluene and characterized by elemental analysis, 1H NMR, 13C NMR and IR spectroscopy. These complexes were used as catalysts for the addition of sodium tetraphenylborate to aromatic ketones and corresponding tertiary alcohols were obtained in good yields.

■ A Diversity-Oriented Approach to 1H-Pyrazole-4,5-diols, 4-Hydroxy-3H-pyrazol-3-ones, and Phenylhydrazones from Key Intermediate 4-Acetyloxy-3H-pyrazol-3-one

Eiichi Masumoto, Fumi Okabe, Toshihiro Fujioka, Kenji Yamagata, and Hiroshi Maruoka*

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

An approach to 1H-pyrazole-4,5-diols 4a−d, 4-hydroxy-3H-pyrazol-3-ones 5a−d, and phenylhydrazones 6a−d from key intermediate 4-acetyloxy-3H-pyrazol-3-one 3a is described. 4-Alkylidene-3H-pyrazol-3-ones 1a−c were reacted with m-chloroperbenzoic acid in the presence of potassium carbonate to give the corresponding spiroepoxide-3H-pyrazol-3-ones 2a−c. Treatment of 2a with acid anhydride such as acetic, propionic, butyric, and pentanoic anhydride in the presence of boron trifluoride diethyl etherate led to the corresponding 4-acyloxy-3H-pyrazol-3-ones 3a−d. The reactions of 3a with α-chloroketones, ketones, and/or secondary amines gave the corresponding 4a−d, 5a−d, and 6a−d.

■ Synthesis of 2-Aryl- and 6-Heteroaryl-1,3-di(4-pyridyl)azulenes by Katritzky’s Pyridylation of 2-Aryl- and 6-Heteroarylazulenes

Taku Shoji,* Akifumi Maruyama, Shunji Ito, Tetsuo Okujima, Masafumi Yasunami, Junya Higashi, and Noboru Morita

*Department of Chemistry, Faculty of Science, Shinshu University, Asahi 3-1-1, Matsumoto, Nagano 390-8621, Japan

Abstract

Preparation of 2-aryl- and 6-heteroarylazulenes 2–6 and 8–10 was established by the palladium-catalyzed cross-coupling reaction of the corresponding haloazulenes with lithium aryl- and heteroarylmagnesium ate complexes, which were readily prepared from the corresponding aryl and heteroaryl halides. The reaction of 2–6 and 8–10, except for 3 and 8, with pyridine in the presence of Tf2O, followed by treatment with KOH in MeOH afforded the corresponding 2-aryl- and 6-heteroaryl-1,3-di(4-pyridyl)azulenes 11–16 in good yields.

■ 1-Hydroxyethylhalenaquinone: A New Proteasome Inhibitor from the Marine Sponge Xestospongia sp.

Michiko Yamakuma, Hikaru Kato, Kanae Matsuo, Ahmed H. El-Desoky, Tetsuro Kawabata, Fitje Losung, Remy E. P. Mangindaan, Nicole J. de Voogd, Hideyoshi Yokosawa, and Sachiko Tsukamoto*

*Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan

Abstract

A new halenaquinone derivative, 1-hydroxyethylhalenaquinone (1), was isolated from the marine sponge Xestospongia sp. as a proteasome inhibitor together with three known compounds, halenaquinone (2) and 3-ketoadociaquinones A (3) and B (4). 1-Hydroxyethylhalenaquinone (1) was the first halenaquinone derivative containing an alkyl group at the keto-furan C-1 position. Compounds 1 and 2 inhibited the chymotrypsin-like activity of the proteasome with IC50 values of 0.19 and 0.63 μM, respectively, whereas 3 or 4, each containing a thiomorpholine 1,1-dioxide moiety, scarcely inhibited its activity, even at a concentration of 5 μM.

■ Synthesis of 7-Amino-5,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile Derivatives Based on the Reaction of 4-Chloro-5-lithio-6-methoxypyrimidines with 2-(Arylmethylidene)propanedinitriles

Kazuhiro Kobayashi,* Shohei Yuba, Aina Taniguchi, Hiroki Inouchi, Hidetaka Hiyoshi, and Kazuto Umezu

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

Abstract

This paper describes a simple and efficient method for the preparation of 7-amino-5,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile derivatives starting from readily available and inexpensive chemicals. Thus, the reaction of 4-chloro-5-lithio-6-methoxypyrimidines, generated by the treatment of 4-chloro-6-methoxypyrimidines with LDA, with 2-(arylmethylidene)propanedinitriles in THF at –78 ˚C provided the corresponding conjugate addition products, 2-[aryl(4-chloropyrimidin-5-yl)methyl]propanedinitrile derivatives, in fair to good yields. These adducts were then treated with alkylamines in refluxing 1,2-dimethoxyethane (DME) in the presence of triethylamine to result in the formation of the desired products in moderate to fair yields.

■ Two New Triterpene Saponins from the Tubers of Stachys sieboldii

Hyeon Kyung Cho, Chung Sub Kim, Won Se Suh, Ki Hyun Kim, and Kang Ro Lee*

*Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, 300 Chunchun-dong, Jangan-ku, Suwon 440-746, Korea

Abstract

Chemical investigation of the MeOH extract of tubers of Stachys sieboldii MIQ. (Labiatae) led to two new triterpene saponins (1 and 2) named sieboldii saponin B and C, together with six known triterpenes (3-8). The structural elucidation of the new compounds was based on MS, 1H- and 13C-NMR, and 2D NMR analysis (1H-1H COSY, HMQC, HMBC, and NOESY) as well as acid hydrolysis. All the isolated compounds 1-8 were reported from this source for the first time.