HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Regular Issue
Vol. 32, No. 12, 1991
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■ Studies with Plant Cell Cultures of Podophyllum peltatum L. I. Production of Podophyllotoxin, Deoxypodophyllotoxin, Podophyllotoxone, and 4’-Demethylpodophyllotoxin
James P. Kutney,* Masao Arimoto, Gary M. Hewitt, Terence C. Jarvis, and Ko Sakata
*Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, B.C. V6T 1Z1, Canada
Abstract
Podophyllotoxin (1) isolated from living plants of Podophyllum peltatum L., is presently the starting material for the commercial production of the clinical anti-cancer drug etoposide. A two-step chemical conversion of 1 affords the analogue, 4’-demethylepipodophyllotoxin (2) and the latter, via a five step chemical process, provides this important drug. The direct production of 1 and/or its appropriate analogues via processes which do not depend on the living plant would provide an attractive alternative route to this compound. The first successful development of a stable plant cell culture line of P. peltatum which provides 1 and its analogues, deoxypodophyllotoxin (3), podophyllotoxone (4) and 4’-demethylpodophyllotoxin (5), via fermentation techniques is described.
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■ Diastereoselective Synthesis of 2,6-Disubstituted 3-Hydroxy Piperidine Derivatives by an Application of Radical Cyclization
Yoko Yuasa, Shinzo Kano, and Shiroshi Shibuya*
*Tokyo College of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
N-[α-(2-Bromo-1-butenyl)-α-methyl]oxazolin-2-one (7) and N-[α-(2-bromo-1-butenyl)-α-pyranyloxyethyl]oxazolin-2-one (14), obtained by starting with ethyl acetoacetate, were treated with tributyltin hydride in the presence of AIBN afforded the cyclization products (8) and (15), respectively, with high diastereoselectivity. Conversion of the 8-methyleneoxazolidinopiperidine (15) to the 6-hydroxyethyl-2-hydroxymethyl-3-hydroxypiperidine derivative (18) was described.
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■ New Entry to Diastereoselective Synthesis of β,γ-Disubstituted γ-Lactones. Application to "Self-immolative" Enantioselective Synthesis of 5-Alkylbutenolides
Tsutomu Yokomatsu, Yuko Yuasa, Shinzo Kano, and Shiroshi Shibuya*
*Tokyo College of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
Photo-initiated radical allylation of γ-phenylthio-γ-lactones (5a,b and 6b), derived from 3-hydroxy-4-(phenylthio)butyrates, gave trans β-oxygenated γ-allyl-γ-lactones (7a,b) in high degree of diastereoselectivity. The method was applied to enantioselective synthesis of (R)-5-(2-hydroxyethyl)-2,5-dihydro-2-furanone (11) with high optical purity.
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■ Thiyl Radical Induced Cyclization of Dienylamides for Lactam Synthesis
Takeaki Naito,* Yuko Honda, Okiko Miyata, and Ichiya Ninomiya
*Kobe Women's College of Pharmacy, Motoyamakita, Higashinada, Kobe 658-8558, Japan
Abstract
A series of dienylamides have been found to undergo radical cyclization when irradiated in the presence of diphenyl disulfide and thiophenol. The present method provides an attractive entry to the preparation of lactams from easily available dienylamides.
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■ The Synthesis of New Heteropolycyclic Quinolone by Twofold Photocyclization: Methoxycarbonylnaphtho[2”,1”: 2’,3’-b]thieno[4’,5’: 2,3]thieno[5,4-c]quinolin-6(5H)-one
Grace Karminski-Zamola,* Davorka Pavlicic, Miroslav Bajic, and Nikola Blazevic
*Organic Chemistry Department, Faculty of Technology, University of Zagreb, Marulicev trg 20, 41000 Zagreb, Croatia
Abstract
New heterocyclic ring system namely 12-methoxycarbonylnaphtho[2”1”‘: 2’,3’-b]thieno[4’,5’: 2,3]thieno[5,4-c]quinolin-6(5H)-one (11) is prepared by multistep synthesis introducing twofold photochemical cyclization.
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■ Alternative Routes to Vincamine
András Nemes,* László Czibula, György Visky, Mária Farkas, and János Kreidl
*Chemical Works of Gedeon Richter Ltd., Budapest 10, P. O. Box 27, H-1475 Budapest, Hungary
Abstract
The preparation of vincamine (1a) via indoloquinolizine propionic esters (7) is discussed. A new synthesis of the starting material methyl 2-acetoxyacrylate and an oxidative transformation of 7b to 1a are described and an alternatvie, more efficient route is reported.
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■ One Step Synthesis of Bicycloalkapyrazines Using Dinitriles with Low-Valent Titanium
Jian-Xie Chen, Jian-Ping Jiang, Wei-Xing Chen,* and Tsi-Yu Kao
*Deaprtment of Chemistry, Nanjing University, Nanjing 210093, China
Abstract
Preparative methods of obtaining bicycloalkapyrazines (2) by the low-valent titanium induced reductive cyclization of dinitriles (1), and for obtaining bi(azacycloalka)pyrazines (5) from N,N-bis(2-cyanoethyl)aromatics amines (4) are presented.
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■ A Practical Synthesis of Isotopically Labelled 1-(4-Isothiocyanatophenyl)-4-(t-butyl)-2,6,7-trioxabicyclo[2.2.2]octane, a Probe for the Benzodiazepine Receptor Coupled Chloride Ionophore
Brian R. de Costa, Anita Lewin, Joyce A. Schoenheimer, Phil Skolnick, and Kenner C. Rice*
*Building 8, Room B1-23, Laboratory of Medicinal Chemistry, National Institutes of , Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0815, U.S.A.
Abstract
An efficient synthesis of high specific activity [3H]1-(4-isothiocyanato-3,5-ditritiophenyl)-4-(t-butyl)-2,6,7-trioxabicyclo[2.2.]octane ([3H]-1), an affinity ligand for the benzodiazepine (BZ)-coupled γ-aminobutyric acid (GABA)-gated chloride channel, was achieved starting with methyl p-aminobenzoate and 3-(t-butyl)-3-oxetanemethanol. A key step in the reaction sequence utilized the azide group as a latent aromatic amine allowing synthesis of 1-(4-amino-3,5-ditritiophenyl)-4-(t-butyl)-2,6,7-trioxabicyclo[2.2.2]octane ([3H]-18) via boron trifluoride etherate catalysed isomerization of 3-(t-butyl)-3-(3,5-dibromo-4-azidobenzoyloxymethyl)oxetane (15) to 1-(3,5-dibromo-4-azidophenyl)-4-(t-butyl)-2,6,7-trioxabicyclo[2.2.2]octane (17). Model experiments performed in an attempt to use unprotected or trifluoroacetamide protected aromatic amines in this sequence of reactions were unsuccessful.
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■ One-Pot Synthesis of New Unsymmetrical β-Heteroaryl-o-divinylbenzenes
Marija Sindler-Kulyk,* Zdenka Stiplosek, Dragana Vojnovic, Biserka Metelko, and Zeljko Marinic
*Organic Chemistry Department, Faculty of Technology, University of Zagreb, Marulicev trg 20, 41000 Zagreb, Croatia
Abstract
By Wittig reaction of o-xylylenebis(triphenylphosphonium bromide) (1) with aldehydes (2) and formaldehyde in the presence of base, unsymmetrically substituted o-divinylbenzenes (3) have been prepared in one pot.
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■ Conversion of 2-Iodoaniline into (Z)-3-Methylene-2,3-dihydroindole Derivatives
Fen-Tair Luo* and Ren-Tzong Wang
*Institutue of Chemistry, Academia Sinica, 128, Yan-Chiu-Yuan Road, Sec II, Nankang, Taipei,11529, Taiwan, R.O.C.
Abstract
Treatment of N-(2-iodophenyl)-N-2-propynyl-p-tolylsulfonamide with various organozinc chlorides in the presence of palladium acetate, triphenylphosphine, and 1 equiv. of triethylamine in tetrahydrofuran gives (Z)-3-alkylidene-2,3-dihydroindoles via intramolecular Heck-type reaction and successive cross coupling reactions.
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■ Reaction of α-Bromoacetophenone Phenylsulfonylhydrazones. A New Synthetic Route to 2-Arylimidazoisoquinolines and -quinolines
Suketaka Ito,* Akikazu Kakehi, and Toshikazu Miwa
*Depatment of Indusrial Chemistry, Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553, Japan
Abstract
2-Arylimidazo[2,1-a]isoquinolines and -[1,2-a]quinolines were obtained in good to moderate yields by the reaction of the title hydrazones with isoquinoline and quinoline, respectively.
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■ 10,11-Epoxy-3-methyl-1,2,3,4-tetrahydro-4a,10b-propanobenzo[f]isoquinolin-12-ones: A Novel Type of Opioid Analgesics — Synthetic Approach and Structure Elucidation
Martin Kratzel* and Horst Völlenkle
*Institut für Pharmazeutische Chemie, Universität Wien , Pharmaziezentrum, Althanstraβe, 10 A-1090 Wien, Austria
Abstract
The title compounds were obtained by nucleophilic cyclopropane ring opening and intramolecular Hofmann reactions, starting from 7,14-cyclodihydrocodeinone (1). An X-ray analysis of 10,11-epoxy-9-methoxy-3-methyl-1,2,3,4-tetrahydro-4a,10b-propanobenzo[f]isoquinolin-12-one dimethyl acetal (3) was performed as basis of molecular modeling studies.
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■ Synthesis of Fused Aminotetrahydrocarbazole Compounds
Yasuo Shimoji,* Fujio Saito, Kuniyuki Tomita, and Yasuhiro Morisawa
*Sankyo Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
Abstract
Intramolecular Diels-Alder reaction of 3-(1H-indol-3-yl)-2-propenoates having olefinic substituents at the 1-position of the indole ring gave stereoselectively pentacyclic fused indole compounds in good yield. Aminotetrahydrocarbazoles derivatives (8, 21, 22) were obtained by Curtius rearrangement via carboxylic acid derivatives. Some of these compounds showed interesting pharmacological activity such as antiarrhythmic activity.
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■ Copper (I) Iodide-promoted Cyclization of Enaminones. Synthesis of 1,2,3,4-Tetrahydro-4-oxo-β-carbolines
Shyh-Chyun Yang, Huey-Min Wang, Ching-Shwu Kuo, and Ling-Ching Chen*
*Graduate Institute of Pharmaceutical Sciences, Kaohsiung Medical College, 100 Shih Chuen 1st Rd., Kaohsiung 80708, Taiwan, R.O.C.
Abstract
Anions derived from the N-2-bromoaryl-substituted enaminones were found to undergo smooth cyclization to give 1,2,3,4-tetrahydro-4-oxo-β-carbolines when heated with copper (I) iodide in hexamethylphosphoric triamide.
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■ Synthesis of Halohydroxypyrazines and Their Synthetic Utility
Yutaka Aoyagi, Takako Fujiwara, and Akihiro Ohta*
*Tokyo College of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
Treatment of hydroxypyrazines with N-halosuccinimide (NXS; X = Cl, Br, I) in N,N-dimethylformamide (DMF) at room temperature afforded halohydroxypyrazines in good yields. Their synthetic utility was examined.
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■ Enaminones in the Preparation of 1,2-Diazetidin-4-ones
John V. Greenhill and Edward C. Taylor*
*Department of Chemistry, Princeton University, Princeton, New Jersey 08544, U.S.A.
Abstract
A new procedure for the preparation of 1,2-diazetidin-4-ones via ring closure of N1-(2-chloroacyl)-N1-methyl-N2-(3-oxocyclohexenyl)hydrazines has led to the preparation of a 4,4-disubstituted 1,2-diazetidin-4-one.
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■ Studies on the Alkaloids from Aconitum karakolicum Rap.
Baoshan Huang, Hongcheng Wang, Aina Lao, Yasuo Fujimoto,* and Makoto Kirisawa
*College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan
Abstract
A new C20-diterpene alkaloid, karakomine (1) along with two known compounds, songorine (2) and neoline (3), have been isolated from the roots of Aconitum karakolicum Rap. The structure of karakomine was determined by 1D and 2D nmr spectroscopic analyses.
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■ Phthalide Dimers from Ligusticum chuangxiong Hort.
Takashi Naito,* Takao Katsuhara, Kazuaki Niitsu, Yukinobu Ikeya, Minoru Okada, and Late Hiroshi Mitsuhashi
*Research Institute for Biology and Chemistry, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan
Abstract
Two new phthalide dimers, senkyunolide O (1) and senkyunolide P (2), along with three known phthalide dimers were isolated from the rhizome of Ligusticum chuangxiong Hort. On the basis of spectral analyses and chemical methods, the structures of these compounds were determined.
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■ Transition Metal-Diene Complexes in Organic Synthesis, Part 9. First Total Synthesis of Carbazomycinal
Hans-Joachim Knölker* and Michael Bauermeister
*Institute für Organic Chemie, Universität Karlsruhe Lehrstubl I, Richard-Willstätter-Allee, 7500 Karlsruhe, Germany
Abstract
Using consecutive iron-induced C-C and C-N bond formation the first total synthesis of carbazomycinal (carbazomycin E) was accomplished.
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■ Synthesis of 2’,3’-Didehydro-2’,3’-dideoxynucleosides Utilizing Coupling Reactions between Nucleic Bases and Phenylthio-substituted 2,3-Dideoxyribose
Hiroshi Kawakami,* Takashi Ebata, Koshi Koseki, Katsuya Matsumoto, Hajime Matsushita, Yoshitake Naoi, and Kazuo Ito
*Life Science Research Laboratory, Japan Tobacco Inc., 6-2, Umegaoka, Midori-ku, Yokohama, Kanagawa 227-8512, Japan
Abstract
Stereoselectivities in coupling reactions between silylated pyrimidine bases and 3- or 2-α-phenylthio-2,3-dideoxyribose were examined. In the former case, no stereoselectivities were observed when the coupling reactions were performed either with 1-chlorosugar in an SN2 mode or in the presence of Lewis acids as catalyst in an SN1 mode. Coupling reaction with 2-α-phenylthio-2,3-dideoxyribose in the presence of Lewis acids, especially SnCl4, proceeded with good stereoselectivity to give anomeric mixtures of α:β = 1:9. All these nucleosides were converted to 2’,3’-didehydro-,2’,3’-dideoxynucleosides by oxidation to sulfoxides followed by thermal elimination of sulfenic acid.
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■ Regioslective Hydride Reduction of 2-(N-Cyanoimino)thiazolidine Derivatives
Chuzo Iwata,* Michitaro Fujimoto, Mayumi Watanabe, Tetsuya Kawakami, Noriko Maeda, Takeshi Imanishi, and Tetsuaki Tanaka
*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan
Abstract
Treatment of 3-alkyl-2-(N-cyanoimino)thiazolidines with lithium aluminum hydride caused reductive cleavage of the imino double bond to afford 3-alkylthiazolidines, while diisobutylaluminum hydride reduction of 3-alkyl- and 3-sulfonyl derivatives resulted in the nitrile reduction or imino-nitrile bond cleavage to give 2-formyliminothiazolidines and/or 2-iminothiazolidines.