HETEROCYCLES

■ Contents

■ Total Synthesis of Styelsamine C, a Cytotoxic Fused Tetracyclic Aromatic Alkaloid

Shinsuke Nakahara* and Akinori Kubo

*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

A cytotoxic fused tetracyclic aromatic alkaloid, styelsamine C (3) from the ascidian Eusynstyela latericius, was synthesized utilizing biaryl cross-coupling reaction.

■ Intermolecular Photoaddition Reaction of Benzenecarbothioamide with γ,δ-Unsaturated Ketones: A Novel Formation of Cycloalkane-fused Pyridine Derivatives by Photoinduced Reaction

Kazuaki Oda,* Rikiji Nakagami, Michiko Haneda, Naozumi Nishizono, and Minoru Machida

*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

Irradiation of benzenecarbothioamide with 2-(2-alkenyl)-cycloalkanone in benzene gives cycloalkane-fused pyridine derivatives in moderate yields.

■ Approach to the Synthesis of (+)-Ifforestine. Model Studies Directed at the Tetracyclic Framework

Gregory H. P. Roos* and Kim A. Dastlik

*Chemistry Department, Sultan Qaboos University, P.O.Box 36 Al-Khoud 123, Sultanate of Oman

Abstract

In order to design an effective asymmetric synthesis of (+)-ifforestine, model approaches to the construction of the tetracyclic ring system have been investigated. These studies have identified two key synthons, a functionalized isatoic anhydride and a pipecolic acid derivative, as suitable AB- and D-ring portions for creation of the crucial diazopinedione C-ring.

■ Synthesis and X-Ray Analysis of Isomeric Diazadithiapentacenes

Malgorzata Nowak, Krystian Pluta,* Christian Kloc, and Theo Siegrist

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

Abstract

The isomeric diazadithiapentacenes (3) and (4) were obtained in reactions of 2-chloro-3-bromoquinoline (5) with selected sulfur reagents in various conditions. The 1,4-dithiin ring opening in diazadithiapentacene (3) led to 2,3’-diquinolinyl sulfide or (via the Smiles rearrangement stage of the S→S type) to 3,3’-diquinolinyl sulfide or to diazadithiapentacene (4) depending on reaction conditions. The X-Ray study of pentacenes (3) and (4) revealed non-planar and folded structures along the central sulfur-sulfur axis. The central six-membered ring is in a boat conformation.

■ Enantioselective Synthesis of Mono- and Disubstituted 3,6-Dihydro-2H-pyrans and 5,6-Dihydropyran-2-ones

Irene Izzo,* Pasquale Del Gaudio, Carmela Della Monica, Maria Squitieri, and Francesco De Riccardis*

*Department of Chemistry, University of Salerno, Via S. Allende I-84081 Baronissi(SA), Italy

Abstract

An enantioselective synthesis of mono- and disubstituted 3,6-dihydro-2H-pyrans and 5,6-dihydropyran-2-ones was achieved via ring-closing olefin metathesis, employing Grubb’s catalyst, and starting from ready available chiral building blocks.

■ 1H- and 1-Alkyl-1,4-dihydro-4-oxo-3-alkylthioquinolines from 1,4-Dihydro-4-oxo-3’-alkylthio-3,4’-diquinolinyl Sulfides

Ewa Bebenek, Elwira Chrobak, and Andrzej Maslankiewicz*

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

Abstract

Quinolinones (1) were N-alkylated with alkyl iodides in DMSO or DMF in the presence of potassium methoxide to N-alkyl derivatives (3) (78-98%). One-pot method was elaborated allowing to transform compound (1a) into the mixture of 1-alkyl-3-alkylthio-4(1H)-quinolinones (8) (55-76%) and 4-methoxy-3-methylthioquinoline (4a) (83-90 %).
Potassium methoxide in DMSO causes sequentially fission of diquinolinyl sulfide (1) to the mixture of dipotassium salt of 3-mercapto-4-quinolinone (9) and (4) and then O-demethylation of 4 to potassium salt of 3-alkylthio-4-quinolinone (5), which could be transformed after S-alkylation of 9 and neutralization to 3-alkylthio-4-quinolinones (6). This one-pot procedure permits to convert both quinoline-units of 3,4’-diquinolinyl sulfide (1) to 6 with total yield of 60-78%.

■ New Luteolin 3’-O-Acylated Rhamnosides from Leaves of Bursera graveolens

Tsutomu Nakanishi,* Yuka Inatomi, Satomi Arai, Takeshi Yamada, Hideyuki Fukatsu, Hiroko Murata, Akira Inada, Nobuyasu Matsuura, Makoto Ubukata, Jin Murata, Munekazu Iinuma, Miguel Angel Perez Farrea, and Toshiyuki Tanaka

*Gifu Prefectrual Institute of Health and Environmental Sciences, 1-1 Nakafudogaoka, Kakamigahara, Gifu 504-0838, Japan

Abstract

Three new luteolin 3’-O-rhamnopyranosides with an acetyl and/or a p-coumaroyl groups were isolated from leaves of Bursera graveolens along with five known flavonol glycosides, β-sitosterol 3-O-β-glucopyranoside and α-amyrin. The structures of the isolated compounds were determined by spectroscopic analysis. Their inhibitory activities for the Maillard reaction were also investigated.

■ Structural and Conformational Studies of 3-(6-Chloropyridazin-3-yl)-N,N-dimethylpiperazinium Iodide and 3-(6-Chloropyridazin-3-yl)-N,N-dimethylhomopiperazinium Iodide with Central Nicotinic Action

Roberto Artali, Gabriella Bombieri,* and Fiorella Meneghetti

*Institute of Pharmaceutical Chemistry, University of Milano, Viale Abruzzi 42, 20131 Milano, Italy

Abstract

The structural characteristics of 3-(6-chloropyridazin-3-yl)-N,N-dimethylpiperazinium iodide (3c) and 3-(6-chloropyridazin-3-yl)-N,N-dimethylhomopiperazinium iodide (4c) have been investigated in order to understand their actions at the nAchR receptor. The results of the X-Ray molecular structures and of the conformational analysis have been compared with the structure of epibatidine that represents one of the most potent nicotinic agonist.

■ Synthesis of Naphth[3,2,1-cd]indole by Heck Cyclization of 2-Methoxycarbonyl-3-benzoylindoles

Yasuyoshi Miki,* Hideaki Shirokoshi, Mikito Asai, Yoshiyuki Aoki, and Hana Matsukida

*Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1, Kowakae, Higashi-Osaka 577-8502, Japan

Abstract

Reaction of 1-benzylindole-2,3-dicarboxylic anhydride with 1,3-dimethoxybenzene in the presence of titanium(IV) chloride gave the corresponding 3-(2,4-dimethoxybenzoyl)indole-2-carboxylic acid as the sole product. This carboxylic acid could be converted to naphth[3,2,1-cd]indole.

■ Spectroscopic Analysis of Imidazolidines. Part IV: ¹³C-NMR Spectroscopy

Isabel A. Perillo,* Graciela Buldain, and Alejandra Salerno

*Department of Organic Chemistry, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956 (1113) Buenos Aires, Argentina

Abstract

¹³C NMR spectra of a series of 1,3-di- and 1,2,3-trisubstituted imidazolidines with aryl, alkyl and aralkyl groups are analyzed and their spectroscopic parameters correlated with conformational features. Assignments were confirmed by means of two dimensional spectra of heteronuclear correlation HMQC and HMBC. Heterocyclic carbons are highly influenced by the nature of the substituent on adjacent nitrogen. Thus, carbon atoms adjacent to a nitrogen substituted with an alkyl or aralkyl group appear in the spectrum at δ ca. 53 ppm as double doublets with ¹J_C-H 134 and 145 Hz, due to a definite orientation of the substituent. Instead, carbon atoms adjacent to an N-aryl group appear at higher fields (δ ca. 47 ppm) as triplets with ¹J_C-H ca 141-143 Hz.

■ Cyclocondensations of β-Aroylacrylic Acids with Heterocyclic O-Diamines

Nadezhda Kolos, Tatyana Beryozkina, and Valeriy Orlov*

*Department of Organic Chemistry, V. N. Karazin Kharkiv National University, Svobody sq. 4, 61077 Kharkiv, Ukraine

Abstract

Reaction of β-aroylacrylic acids (6a—c) with 2,3-diaminopyridine (7), 5,6-diamino-1,3-dimethyluracil (8) and 2,5,6-triamino-4-oxopyrimidine (9) was studied. 1,3-Dimethyl-5,8-dihydro-1H,3H,6H-pteridine-2,4,7-trione (11c) and 2-amino-4-hydroxy-6-(2-oxo-2-phenylethyl)-5,8-dihydro-6H-pteridin-7-one (13a) were rearranged into pteridin-6-ylideneacetic acids (12c) and (14a) respectively. Reaction of α,β-dibromo-β-benzoylpropionic acid (15) with diamine (8) led to 8-benzoylpurine (17) via the step of the formation of enaminoketone (16).

■ Synthesis, Spectroscopic Studies, and Crystal Structure of 3-(1-Hydroxyiminoethyl)-1-phenyl-4-hydro-1,2,4-triazine-5,6-dione Methanol Solvate

Ahmad S. Abushamleh, Abdel-Fattah Shihada,* and Frank Weller

*Chemistry Department, Faculty of Sciences and Arts, The Hashemite University, Zarqa, P.O. Box 150459, Zarqa, 13115, Jordan

Abstract

3-(1-Hydroxyiminoethyl)-1-phenyl-4-hydro-1,2,4-triazin-5,6-dione, has been prepared from the chiral 1-phenyl-3-acetyloxime-5-benzyl-4,5-dihydro-1,2,4-triazin-6-one in the presence of organotin(IV) compounds in methanol solution. It crystallizes as a 1:1 methanol solvate in the monoclinic space group P 2₁/c with the lattice parameters: a = 1517.6(1), b = 563.64(3), c=1500.34(13) pm and β = 90.35(1)°. The molecules, in which the heterocyclic ring is planar, are dimer via strong oxime-methanol and methanol-dione hydrogen bonds and by additional N–H---O bridges linking the heterocyclic rings.

■ New Steroidal Glycosides from Parepigynum funingense

Yan Hua, Hui Min Zhong, and Chang Xiang Chen*

*State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Heilongtan, Kunming 650204, Yunnan, China

Abstract

Six new steroidal glycosides with an unusual framework, funingenosides E (1), F (2), G (3), H (4), I (5) and J (6) were isolated from the roots of Parepigynum funingense. Their structures were elucidated by a combination of 1D and 2D NMR spectral analysis.

■ Metal Chelations in Asymmetric Diels-Alder Reaction

Kyoo-Hyun Chung,* Chan-Kook Chu, and Min-Ho Chang

*Department of Chemistry, Inha University, 253, Yonghyundong Namgu, Inchon 402-751, Korea

Abstract

In the presence of chiral catalysts, Diels-Alder reaction of a N-acryloyl chiral dienophile with cyclopentadiene gave the corresponding endo norbornenecarboxamide with high diastereoselectivity. In the reaction, 8-membered chelation was effective enough to distinguish transoid and cisoid conformation in the presence of divalent Lewis acid catalysts, such as TiCl₄.

■ Metallocyclodextrins and Related Species

Wanda Sliwa* and Tomasz Girek

*Institute of Chemistry and Environmental Protection, Pedagogical University, Al. Armii Krajowej 13/15, 42-201 Czestochowa, Poland

Abstract

In first part of the review cyclodextrin (CD) complexes with copper and platinum ions are presented, followed by those with lanthanide ions. Then CD complexes of ferrocenes and of ruthenium ions bound with bipyridine and phenanthroline ligands are described. The next parts of the paper deal with CD complexes with metal ions bound in cyclens or porphyrins. At last some examples of CD-modified nanoparticles are given.