HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Arnold Brossi's Special Issues, Vol. 39, No. 1, 1994
Published online:
■ Diels-Alder Reaction of the N-Protected 3-Phenylthio-2(1H)-dihydropyridinone Derivatives
Yasuhiro Torisawa, Masako Nakagawa,* Hideo Takami, Toshiaki Nagata, Mohamed Ayman Ali, Tohru Hino, and Shunji Naruto
*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
Efficient methods for the preparation of N-protected 3-phenylthio-2(1H)-dihydropyridinones from 2-piperidone and their Diels-Alder reaction with 2-trimetylsilyloxybutadiene are described. The role of the electron-withdrawing N-protecting group in the dienophiles is rationalized in terms of the lowered energy level in LUMO.
Published online:
■ Identification and Synthesis of Major Oxidative Degradation Products of Tiagabine
Gary Callen, Mukund S. Chorghade,* Elaine C. Lee, Peter G. Nielsen, Hans Petersesn, and Abu Rustum
*Abbott Laboratories, Abbott Park, N. Chicago, IL60064, U.S.A.
Abstract
Tablet formulations of tiagabine (an anti-epileptic drug currently in Phase III trials) revealed the presence of some degradation products. The isolation, spectroscopic characterization and synthesis of these products are described.
Published online:
■ Synthesis of Optically Active 9-Methoxy-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxamide Derivatives via Asymmetric Diels-alder Reaction of a Chiral Sulfinylmaleimide with 9-Methoxyanthracene
Tamiko Takahashi, Jun Sugita, Takako Hirano, and Toru Koizumi*
*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan
Abstract
Optically active 9-methoxy-9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxamide derivatives (1a-c) were synthesized via an asymmetric Diels-Alder reaction of a chiral sulfinylmaleimide (2) with 9-methoxyanthracene (3).
Published online:
■ New Acridone Alkaloids from Citrus Plant
Yuko Takemura, Junko Kuwahara, Noriko Nagareya, Motoharu Ju-ichi,* Mitsuo Omura, Ichiro Kajiura, Chihiro Ito, and Hiroshi Furukawa
*School of Pharmaceutical Science, Mukogawa-Women's University, 11-68 Koushien Kyuban-Cho, Nishinomiya, Hyogo 663-8179, Japan
Abstract
Two new acridone alkaloids, named marshdine (1) and marshmine (2), were isolated from the root of Marsh grapefruit (Citrus paradisi Macf.) and their structures were elucidated by spectroscopic method.
Published online:
■ Enantioselective Synthesis of β-Amino Acids. 5. Stereoselective Reaction of Chiral Pyrimidinone Enolates with Aldehydes
Peter Murer, Beat Rheiner, Eusebio Juaristi, and Dieter Seebach*
*Laboratorium fur Organische Chemie, Eidgenossischen Technischen Hochschule, ETH-Zentrum, Universitatstrasse 16 CH-8092 Zurich, Switzerland
Abstract
Hydro-pyrimidinones ((2S,6R)-3) and ((2S)-6) were prepared from methyl crotonate via 3-aminobutanoate, and their corresponding lithium enolate and dienolate derivatives were added to various aldehydes. The high regio- and stereoselectivities observed in these aldol reactions pave the road for the preparation of enantiomerically pure β-hydroxy-β’-amino acids. The structures of the products were confirmed by X-ray crystal structure analysis (eight examples).
Published online:
■ Preparation of Heteroarenecarbonitriles by Reaction of Haloheteroarenes with Potassium Cyanide Catalyzed by Sodium p-Toluenesulfinate
Akira Miyashita,* Yumiko Suzuki, Kiyono Ohta, and Takeo Higashino
*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
Several heteroarenecarbonitriles were prepared by reaction of haloheteroarenes with potassium cyanide catalyzed by sodium p-toluenesulfinate (1) or sodium methanesulfinate (2). In the reaction pathway, the cyanation proceeds through the formation of the sulfonylheteroarenes.
Published online:
■ Reduction of Oxindoles with Sodium Bis(2-methoxyethoxy)aluminium Hydride, a Novel Reducing Agent
Xue-Feng Pei* and Sheng Bi
*Department of Chemistry, Georgetown University, Washington DC 20057, USA
Abstract
1,3-Dimethyl-3-(2’-dimethylaminoethyl)-5-tetrahydropyranyloxyoxindole (5), obtained on C3-alkylation of oxindole (4), was reduced stereoselectively with sodium bis(2-methoxyethoxy)aluminum hydride (Vitride) to carbinolamine (6). Oxindoles (7, 8, 9, 10 and 11) similarly were reduced and cyclized to (±)-N1-noresermethole (13), (±)-O-tetrahydropyranyl-N1-noreseroline (14), (±)-physovenol methyl ether (15), (±)-esermethole (16), and (±)-N1-benzylnoresermethole (17), respectively.
Published online:
■ Nitrosourea Derivatives of 3',4'-Didemethoxy-3',4'-dioxo-4-deoxypodophyllotoxin and Urea Derivatives of 4'-O-Demethylpodophyllotoxin as Potent Inhibitors of Human DNA Topoisomerase II
Makoto Miyahara, Yoshiki Kashiwada, Xin Guo, Hong-Xing Chen, Yung-Chi Cheng, and Kuo-Hsiung Lee*
*Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7360, U.S.A.
Abstract
Nitrosourea derivatives of 3’,4’-didemethoxy-3’,4’-dioxo-4-deoxypodophyllotoxin and urea derivatives of 4’-O-demethylpodophyllotoxin were synthesized and evaluated for their inhibitory activity against DNA topoisomerase II and KB cells. Although the 4β-N’-nitrosoureido compounds demonstrated good inhibitory activity against topoisomerase ll, they were found to possess low activity for protein linked-DNA complex formation ability. On the other hand, the 4β-ureido compounds exhibited better or similar activity compared to 1, etoposide.
Published online:
■ Cesium Fluoride-mediated Claisen Rearrangements of Phenyl Propargyl Ethers: Effect of a Substituent on the Phenyl Ring on the Rearrangement
Tsutomu Ishikawa,* Keiko Nagai, Naoko Ohkubo, and Hisashi Ishii
*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
Methoxy or methoxycarbonyl-subsituted phenyl propargyl ethers were subjected to Claisen rearrangement either in the absence or in the presence of CsF. Substituent effect on the cyclization is discussed
Published online:
■ Synthesis of Fluorinated Analogs of Hematoporphyrin. II
Masaaki Omote, Akira Ando, Mayumi Koyama, Toshiyuki Takagi, and Itsumaro Kumadaki*
*Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata-shi, Osaka 573-0101, Japan
Abstract
With the aim of obtaining a porphyrin derivative useful for diagnosis and therapy of cancer, fluorinated analogs of hematoporphyrin, which had a trifluorohydroxyethyl group in the place of one of the hydroxyethyl groups, were synthesized by acetylation of trifluorohydroxyethyldeuteroporphyrin dimethyl esters, followed by reduction of the acetyl group.
Published online:
■ Structure Activity Relationship in the Colchicine Molecule with Respect to Interaction with the Mammalian Multidrug Transporter, P-Glycoprotein
David F. Tang-Wai, Arnold Brossi, Lee D. Arnold, and Philippe Gros*
*Department of Biochemistry, McGill University, McIntyre Medical Sciences Building, 3655 Drummond Street, Montreal, Quebec H3G 1Y6, Canada
Abstract
Colchicine forms part of a group of structurally unrelated cytotoxic drugs to which P-glycoprotein overexpression confers resistance to, both in cultured cells in vitro and tumor cells in vitro. Modifications of the methoxy groups on the A and C rings modulated cellular toxicity but had no effect on P-gp interaction. Modifications at the C7 position of the B-ring, in particular the removal of the nitrogen atom of the acetamido group, had a dramatic effect. Examination of calculated molar refractivities (CMR) revealed that only compounds showing CMR values greater than 9.7 were P-gp substrates, suggesting a minimal size requirement for efficient interaction with P-gp.
Published online:
■ Chiral NADH Models Derived from Optically Active Amino Alcohols
Georges Dupas, Vincent Levacher, Jean Bouguignon*, and Guy Quéguiner
*Laboratoire de Chimie Organique Fine et Heterocyclique de l'IRCOF, URA 1429 CNRS, INSA de Rouen, BP08, 76131 Mont-Saint-Aignan Cedex, France
Abstract
After a short description of the main characteristics of biomimetic NADH models, the choice of optically active amino alcohols as chiral auxiliaries is justified. The literature results in this field are then reviewed. The results obtained with 1,4-dihydropyridines, annelated models in the thiophene and pyrrole series are particularly discussed. The main factors responsible of a good enantioselectivity are emphasized and applied to the design of a highly enantioselective NADH model in the 1,6-naphtyridinone series.