HETEROCYCLES

■ Contents

■ The Chemical and Biological Properties of Protopine and Allocryptopine

Jan Vacek,* Daniela Walterová, Eva Vrublová, and Vilím Šimánek

*Faculty of Medicine and Dentistry, Department of Medical Chemistry and Biochemistry, Palacký University, Hnevotínská 3, 77515 Olomouc, Czech Republic

Abstract

The isoquinoline alkaloids, protopine and allocryptopine are components of numerous phytopreparations. The wide spectrum of biological activities reported for these alkaloids include multiple actions on the cardiovascular system, anti-thrombotic, anti-inflammatory, anti-spasmodic, neuroprotective, anti-bacterial, anti-viral, anti-fungal and anti-parasitic activities. This review aims to summarize recent knowledge on the basic chemistry, analysis, above biological activities, and application of both alkaloids published within the period 1995-2010.

■ Formal Syntheses of Dihydrocorynantheine and Isorhynchophylline via Proline Catalyzed Mannich-Michael Reaction

Kazuhiro Nagata, Hitomi Ishikawa, Ayako Tanaka, Michiko Miyazaki, Takuya Kanemitsu, and Takashi Itoh*

*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Abstract

Proline catalyzed Mannich-Michael reaction of 3-ethyl-3-buten-2-one with 9-tosyl-3,4-dihydro-β-carboline proceeded in a highly stereoselective manner. The reaction was applied to formal syntheses of dihydrocorynantheine and isorhynchophylline.

■ 2-Methyl- and 2-Dimethylaminoquino[4,3-e]-1,2,4-thiadiazine 4,4-Dioxides – Synthesis, Structure and N-Methylation

Elwira Chrobak, Michał Wlekliński, Andrzej Maślankiewicz,* Joachim Kusz, Maciej Zubko, and Andrzej Zięba

*Department of Organic Chemistry, The Medical University of Silesia, Jagielloñska Str. 4, 41-200 Sosnowiec, Poland

Abstract

Reaction of 4-chloro-3-quinolinesulfonyl chloride (1) with acetamidine or with N,N-dimethyl- and N,N,N'-trimethylquanidine salts led directly or stepwise via 4-chloro-3-quinolinesulfonylguanidine (6a) to the title 2-substituted quino[4,3-e]-1,2,4-thiadiazine 4,4-dioxides (4, 7a, and 8). X-Ray studies proved that 2-methyl derivative 4 exists as the 1H-tautomer while 2-dimethylamino derivative 7a as the 6H-tautomer. Reaction of N-H derivatives 4 and 7a and the pyrido-1,2,4-thiadiazine analog 11a with CH3I/CH3OK/DMF system proceeded at the pyridine-ring nitrogen and led to 6-methylquino derivatives 5 and 7b or the 7-methylpyrido derivative 11b, respectively, as concluded from 2D 1H - 13C NMR data.

■ Copper-Mediated Oxidative Cyclization of Heterocyclically Substituted Aldimines

Daniela Pufky-Heinrich, Michael Ciesielski, Loubna Gharnati, Olaf Walter, and Manfred Döring*

*Institute of Catalysis Research and Technology, Karlsruhe Institute of Technology, Hermann-von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany

Abstract

Copper-mediated cascade reactions were performed with heterocyclically substituted aldimines. These oxidative heterocyclizations include sequences of oxidations and cycloadditions or nucleophilic additions which take place in the coordination sphere of copper ions. When two heterocyclically substituted aldimines were reacted in the presence of copper (II) salts under air, pyridine derivatives were produced. In one case a 1,4-diazatricyclo-[3.2.1.02,7]oct-3-ene was also formed. The basic structure of this new tetracyclic compound contains five new chirale carbon atoms. This cage-like structure has been revealed by X-ray crystallography. The synthesis of 2H-pyrroles by copper-assisted conversions of the aldimines with dimethylacetylene carboxylate or quinones was also described.

■ One-Pot Two-Step Synthesis of N3-Functionalized 3,4-Dihydropyrimidinones in the Presence of TMSCl

Zheng-Jun Quan,* Rong-Guo Ren, Yu-Xia Da, Zhang Zhang, Xiao-Dong Jia, Cai-Xia Yang, and Xi-Cun Wang*

*Gansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070, China

Abstract

Novel 3,4-dihydropyrimidinones modified with N3-alkyloxymethyl, aminomethyl, arylsulfonylmethyl, and azidomethyl groups can be regioselectively obtained over their isomeric N1 compounds in good yields by reaction of 3,4-dihydropyrimidinones with paraformaldehyde and alcohol, amine, sodium ben-zenesulfinate, and sodium azide, respectively, by a one-pot two-step strategy in the presence of chlorotrimethylsilane. The advantages of this method are the sim-ple procedure, the high regioselectivity of the products, no requirement for a base catalyst, and the mild reaction conditions.

■ Novel Synthesis of 2-Alkoxy(Aralkoxy)-5-chloro[1,2,4]triazolo[1,5-a]quinazolines and Their Derivatives

Rashad Al-Salahi* and Detlef Geffken

*Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh-11451, Saudi Arabia

Abstract

2-Alkoxy(aralkoxy)-5-chloro[1,2,4]triazolo[1,5-a]quinazolines have been synthesized. The corresponding 2-alkoxy(aralkoxy)[1,2,4]triazolo[1,5-a]quinazolin-5-ones were chlorinated with either oxalyl chloride or phosphorus oxychloride. The chlorine atom at 5-position of the targeted [1,2,4]triazolo[1,5-a]quinazolines was replaced with multifunctional N-nucleophiles. This provided the preparation of the heterocyclic system bearing a variety of substituents at 5-position.

■ Efficient Synthesis of 2’-O-Cyanoethylated Imidazole C-Ribonucleoside Phosphoramidite: A Practical Building Block for Probing the Catalytic Mechanism of Ribozymes

Lisa Araki, Zheng-yun Zhao, David M. J. Lilley, and Shinya Harusawa*

*Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan

Abstract

A high-yielding synthetic route leading to new 2’-O-cyanoethylated imidazole C-ribonucleoside phosphoramidite (PA) 1 has been developed (41% overall yield in ten steps). This has resulted in a marked improvement of yield compared to unstable 2’-O-TBDMS PA 2. The new synthon PA 1 enables the imidazole moiety to be incorporated into any RNA sequence in principle, and has been used as a practical building block for probing the catalytic mechanism of a ribozyme.

■ Efficient Synthesis of Biflavones Having A Ring-A Ring of Two Flavone Units Using Suzuki Cross-Coupling Reactions

Yoshihito Kohari, Yukio Hoshino, Haruo Matsuyama, and Hiroto Nakano*

*College of Environmental Technology, Muroran Institute of Technology, 27-1 Mizumoto, Muroran, Hokkaido 050-8585, Japan

Abstract

Biflavones having a A ring-A ring of two flavone units were easily prepared by using Suzuki cross-coupling reaction of borylated flavones with bromoflavones or flavone-5-triflate in good to excellent yields.

■ Effect of Oxygen Substituent in the Aniline Part of Benzanilide on the Regioselectivity in Direct Arylation Using Palladium-Phosphine Reagents

Takashi Harayama,* Mariko Asai, Taeko Miyagoe, Hitoshi Abe, Yasuo Takeuchi, Ayako Yamaguchi, and Shinya Fujii

*Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki City, Kagawa 769-2193, Japan

Abstract

This study investigated the effect of oxygen substituents at the 3’-position in the aniline part of 2-iodobenzanilides on the coupling position in its Pd-assisted direct arylation. Benzanilide with methylenedioxy and acetoxy groups yielded the ortho-product formed predominantly by connection to a more hindered carbon. The mechanism is discussed from the perspectives of both steric and coordinated effects.

■ A New Synthetic Strategy for 2-Deoxy-D-ribose via Palladium(II)-Catalyzed Cyclization of Aldehyde

Masahiro Miyazawa,* Ken-ichiro Awasaguchi, Ikuyo Uoya, Hajime Yokoyama, and Yoshiro Hirai*

*Department of Chemistry, Graduate School of Science and Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan

Abstract

We achieved a total synthesis of 2-deoxy-D-ribose through intramolecular Pd(II)-catalyzed cyclization of aldehyde via an unstable hemiacetal intermediate as a key step.

■ An Efficient and Convenient Synthesis of 4,5,6,7-Tetrahydrothieno[3,2-c]pyridines by a Modified Pictet-Spengler Reaction via a Formyliminium Ion Intermediate

Michikazu Kitabatake, Aki Hashimoto, Toshiaki Saitoh, Takehiro Sano, Kunihiko Mohri, and Yoshie Horiguchi*

*Showa College of Pharmaceutical Sciences, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan

Abstract

A synthesis of N-formyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridines (5) was achieved in a highly efficient manner via trifluoroacetic acid catalyzed cyclization of formyliminium ion (4), which was produced by imination of 2-(2-thienyl)ethylamine (1) and a carbonyl compound (2) using titanium(IV) tetraisopropoxide followed by formylation with acetic-formic anhydride in a one-pot procedure. This modified Pictet-Spengler reaction provides a convenient method for preparing 4,5,6,7-tetahydrothieno[3,2-c]pyridines (6) possessing various substituents at C-4.

■ Synthesis of Quinoline-Bearing Ferrocene Derivatives via Friedländer Reaction of Acetyl- and 1,1’-Diacetylferrocenes with o-Amino Aryl Aldehydes

Wentao Gao,* Xiuping Cheng, and Yang Li

*Institute of Superfine Chemicals, School of Chemistry and Chemical Engineering, Bohai University, 19 Keji Road, Jinzhou 121000, China

Abstract

A facile and convenient synthesis of quinolyl-substituted ferrocenes via Friedländer reaction of acetylferrocene or 1,1’-diacetylferrocene with 2-aminobenzaldehyde, 2-aminopiperonal, and (2-aminophenyl)(phenyl) methanone, respectively, with good yields is described.

■ Naphthopyrones from Cultured Lichen Mycobionts of Pyrenula sp.

Yukiko Takenaka, Naotaka Nagakura, Nobuo Hamada, and Takao Tanahashi*

*Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan

Abstract

Spore-derived mycobionts of the lichen Pyrenula sp. were cultivated on a malt-yeast extract medium supplemented with 10% sucrose and their metabolites were investigated. A new naphthopyrone derivative, pyrenulin, as well as toralactone were isolated. Their structures were determined by spectroscopic methods. This is the first instance of the isolation of naphthalene derivatives from lichen mycobionts.