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. 27, No. 3, 1988
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■ Two Crystalline Dimeric Peroxides from Sensitized Photooxidation of 2,5-Dimethylfuran
Yueh-Hsiung Kuo,* Kae-Shyang Shih, Gene-Hsiang Lee, and Yu Wang
*Department of Chemistry, National Taiwan University, Roosevelt Road Section 4, Taipei 106, Taiwan, R.O.C.
Abstract
Sensitized photooxidation of 2,5-dimethylfuran was carried out in acetone end dichloromethane. Two crystalline dimeric peroxides were isolated after purified on silica gel. The elucidation of the structures of two dimeric peroxides was based on their spectral and chemical date and X-ray analysis.
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■ Heterosteroids via Organoiron Complexes: Enantioselectine Synthesis of the 9-(4-Keto-1-methylcyclohex-2-enyl)-8-keto-des-AB-ergosta-14,15-22,23-diene; An Easy Rearrangement of the Title Compound into a 6-Oxo-B-nor-heterosteroid Structure
Enrico Mincione, Paolo Bovicelli, Silvio Cerrini, and Doriano Lamba
*Centro CNR per lo Studio della Chimica delle Sostanze Organiche Naturali, Dipartmento di Chimica, Università degli Studi di Roma "La Sapienza", Piazzale Aldo Moro 5, 00185 Roma, Italy
Abstract
The synthesis via organoiron complexes of the chiral 9-(4-keto-1-methylcyclohex-2-enyl)-8-keto-des-AB-ergosta-14,15-22,23-diene 13, as well as the rearrangement of 4,13 to 6-oxa B-nor heterosteroids are described.
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■ Alkaloid Production in Catharanthus roseus (L.) G. Don Cell Cultures. XIV. The Role of Unstable Dihydropyridinium Intermediates in the Biosynthesis of Bisindole Alkaloids
James Peter Kutney,* Camille Andre Boulet, Lewis Siu Leung Choi, Wlodzimierz Gustowski, Michael McHugh, Jun Nakano, Tamotsu Nikaido, Hiroki Tsukamoto, Gary Maxwell Hewitt, and Roger Suen
*Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, B.C., V6T 1Z1, Canada
Abstract
Employing enzyme systems obtained from Catharanthus roseus cell cultures, experiments relating to the biosynthesis of various bisindole alkaloids are described. Specifically, the enzyme-catalyzed coupling of catharanthine (1) and vindoline (2) to a highly unstable dihydropyridinium intermediate (9), important in the biosynthesis of 3’,4’-anhydrovinblastine (3), leurosine (4), catharine (6), vinamidine (7) and hydroxyvinamidine (8) is presented. Conversions of 9 to these alkaloids and its role in the biosynthesis is discussed. Although catharanthine is well utilized by the enzyme system, catharanthine N-oxide (10), an important intermediate in the chemical coupling of 1 and 2 to afford 9, is not utilized.
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■ Alkaloid Production in Catharanthus roseus (L.) G. Don Cell Cultures. XV. Synthesis of Bisindole Alkaloids by Use of Immobilized Enzyme Systems
James Peter Kutney,* Camille Andre Boulet, Lewis Siu Leung Choi, Wlodzimierz Gustowski, Michael McHugh, Jun Nakano, Tamotsu Nikaido, Hiroki Tsukamoto, Gary Maxwell Hewitt, and Roger Suen
*Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, B.C., V6T 1Z1, Canada
Abstract
Affinity gel bound enzyme systems obtained from Catharanthus roseus cell cultures were employed to establish a high yielding enzymatic system for the coupling of catharanthine (1) and vindoline (2) to 3’,4’-anhydrovinblastina (3) and leurosine (4). Long term preserved activity can be prerenred by this technique, an aspect which may prove important in subsequent utilization of such systems in large scale production.
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■ Alkaloid Production in Catharanthus roseus (L.) G. Don Cell Cultures. XVI. Biotransformation of 3’,4’-Anhydrovinblastine with Catharanthus roseis Cell Cultures and Enzyme Systems
James Peter Kutney,* Bruno Botta, Camille Andre Boulet, Carlos Alberto Buschi, Lewis Siu Leung Choi, Jerzy Golinski, Maria Gumulka, Gary Maxwell Hewitt, Gin Lee, Michael McHuge, Jun Nakano, Tamotsu Nikaido, Jun-ichi Onodera, Ileana Perez, Philip Salisbury, Mahatam Singh, Roger Suen, and Hiroki Tsukamoto
*Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, B.C., V6T 1Z1, Canada
Abstract
Employing cell cultures of Catharanthus roseus and enzyme systems derived from such cultures, a detailed study of the biotransformation of 3’,4’-anhydrovinblestine (3) is described. It is shown that enzymatic conversion of 3 to the isolated end products, the bisindole alkaloids leurosine (4), vinblastine (5), catharine (6), vinamidine (7) and hydroxyvinamidine (8) proceeds initially to the same dihydropyridinium intermediate (9) obtained when the monomeric alkaloids catharanthine (1) and vindoline (2) are enzymatically coupled. These data establish that the overall biosynthetic pathway to the bisindole alkaloids proceeds from 1 and 2 to the initially formed 9 and the latter, under enzymatically controlled oxidation-reduction, affords the alkaloids 3-8. However, when 3 is incubated as substrate, the enzymes are capable of utilizing and converting It into the alkaloids 4-8. In summary, 3 is not a direct biosynthetic precursor of 4-8.
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■ Selenonium Ylides of Cyclopentadiene, Indole and Pyrrole
Klaus Hartke* and Hans Henning Wendebourg
*Institut für Pharmazeutische Chemie, Universität Marburg, Marbacher Weg 6, D-35032 Marburg/Lahn, Germany
Abstract
Selenonium cyclopentadienides 3 have been prepared from (trimethylsilyl)cyclopentadiene and dialkyl or diaryl selenoxides. Selenonium salts of indole and pyrrole are accessible by an electrophilic substitution with selenoxides and trifluoracetic anhydride. In some cases deprotonation leads to stable ylides.
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■ Synthsis of Biologically Active 6-Azaprostacyclin Derivatives
Keisuke Miyajima, Masumi Takemoto, and Kazuo Achiwa*
*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
Biologically active 6-azaprostacyclin derivatives were synthesized by use of 1,3-dipolar cycloaddition as a key step.
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■ Oxidation of Acetylaminoquinolines in Udenfriend’s Oxidation System
Toyo Kaiya, Yutaka Kawazoe,* Machiko Ono, and Shinzo Tamura
*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan
Abstract
Oxidation of 5-acetylaminoquinoline in Udenfriend’s oxidation system gave 3- and 8-hydroxylated derivatives, 5,5’- azoquinoline, and three other products which are supposed to be formed via oxidative cleavage of the aromatic double bonds. The oxidation of 6- and 7-acetylaminoquinolines gave the corresponding 3-hydroxylated derivatives and 5,8-quinone derivatives.
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■ Spiroketal Synthesis. Preparation of Functionalized 1,7-Dioxaspiro[5,5]undecanes
Charles G. Chavdarian,* Lydia L. Chang, and Bruce C. Onisko
*Western Research Center, Stauffer Chemical Company, 1200 S. 47th Street, Box Number 4023, Richmond, CA 94804-0023, U.S.A.
Abstract
5-Oxo-1,7-dioxaspilro[5,5]undecanes can be prepared from γ-butyrolactones and dihydropyran in a two-step process. Condensation of 2-lithiodihydropyran with the appropriate lactone, followed by acid-catalyzed cyclization, affords the spiroketal.
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■ Ion-radical promoted Cyclization of a δ,ε-Vinylimine: The Total Synthesis of (±)-Tuboxenine
Dominique Cartier, Mohammed Ouahrani, Georgette Hugel, and Jean Lévy
*Laboratorie de Pharmacognosie, Facluté de Pharmacie, U.A. n°492 au C.N.R.S., 51, rue Cognacq-Jay, F-51096 Reims Cedex, France
Abstract
3-Oxo-1,2,18,19-tetradehydroaspidospermidine 8b was synthesized by a modification of a previous synthesis of vincadifformine 10. It was cyclized (Na/THF) to 3-oxotuboxenine 22, which was reduced with LiAIH4 to (±)-tuboxenine 1.
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■ The Addition of Cyanide to 1,1,1-Trifluoroacetone: One Step Formation of a Heterocyclic Ring
Nazario Martín, Carlos Seoane, and José L. Soto
*Departamento de Química Orgánica, Facultad de Química, Universidad Complutense de Madridas, Ciudad Universitaria, E-28040 Madrid, Spain
Abstract
The addition of potassium cyanide to 1,1,1-trifluoroacetone results in the one step formation of a novel iminooxolane ring.
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■ An Abnormal Reaction of N-tert-Butoxycarbonyl Group: Mechanistic Consideration for the Preparation of 2-Oxotetrahydro-1,3-oxazine
Yoshitaka Matsubara, Ryuji Yoneda, Shinya Harusawa, and Takushi Kurihara*
*Faculty of Pharmaceutical Science, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
Abstract
Threo- and erythro-selective aldol condensations of 3-aminopropionate (1) with benzaldehyde (2) gave β-hydroxy ester (3) as a mixture of diastersomers (threo/erythro: 79/21 and 26/74). Upon treatment with methanesulfonyl chloride and triethylamine, threo-3 was converted to 2-oxotetrahydro-1,3-oxazine (4) via mesylate, while erythro-3 gave the corresponding mesylate (5). A plausible mechanistic consideration is also described.
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■ Studies on the Synthesis of Preconcenes. The Photo-Fries Rearrangement of Ester of α,β-Unsaturated Carboxylic Acid and meta-Oxygenated Phenols
Miguel A. Miranda,* Jaime Primo, and Rosa Tormos
*Departamento de Química Oránica, Facultad de Farmacia, Av. Blasco Ibañez 13, 46010 Valencia, Spain
Abstract
The photo-Fries rearrangement of a series of aryl esters of α β-unsaturated carboxylic acids 1a,b and 2 has been investigated, in order to explore the possibilities of this reaction as a key step in the synthesis of precocenes and related compounds. In all cases, the photolysis in hexane does not lead to any observable transformation, but in the presence of potassium carbonate takes place a migration of the acyl group to the two ortho-positions. Additionally, trans-cis photoisomerization occurs with the trans-butenoate 1b. The resulting-o- hydroxyketones 4a,: 4b, 4c, 5a , 5b , 5c, and 8 are easily and efficiently cyclized to the corresponding 4-chromanones 6a, 6b, 7a, 7b, and 9. A second photo-rearrangement is observed in the case of 9, although the yield is low, due to deactivation by the carbonyl group. Cyclizatlon of 10 gives rise to the tricyclic dichromanone 11. Compounds 6a and 11 are reduced and subsequently dehydrated by known procedures to afford the active chromenes 3 and 12.
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■ 1.3-Dipolar Cycloaddition of Nitrile Oxides to Chlorosulfonyl Isocynate: Selective Formation of 3-Aryl Substituted 1,2,4-Oxadiazolin-5-ones
Kakulapati Rama Rao, Tiruchirapally Natesan Srinivasan, and Prahlad Balvantrao Sattur*
*Regional Research Laboratory, Hyderabad 500 007, India
Abstract
Aryl substituted nitrile oxides add in a selective way to C=N of chlorosulfonyl isocyanate to afford 3-Aryl-substituted 1,2,4-oxadiazolin-5-ones after hydrolysis.
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■ On 5-Hydroxytetrahydroprotoberberine Derivatives. Synthetic Studies and Stereochemical Elucidation
Dolores Badía, Esther Domínguez,* Ester Lete, María-Jesús Villa, Luis Castedo, and Domingo Domínguez
*Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Páis, Vasco, P.O. Box 644, 48080-Bilbao, Basque Country, Spain
Abstract
Stereochemical characterization of 5-hydroxy-8-methyl-2,3,9,10-tetramethoxyberbines (3) and (4) is established unambiguously on the basis of nmr data, supported by difference NOE measurements. Their synthesis starting from the adequate 3-aryltetrahydroisoquinoline (1) is reported.
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■ Chemistry of C-Heteroarylhydrazidoyl Halides. Synthesis and Reactions of N-(p-Nitrophenyl)-C-(2-thienyl)-formohydrazidoyl Halides
Hamdi M. Hassaneen,* Hiyam A. H. Mousa, Nosrat M. Abed, and Ahmad S. Shawali
*Girls College, Science Department, General Presidency for Girls Education, Riyadh, Saudi Arabia
Abstract
Synthesis of C-(2-thienyl)-N-(p-nitrophenyl)formohydrazidoyl chloride 5a and its bromide analog 5b is described. Both 5a and 5b react with oxygen, sulfur and nitrogen nucleophiles in ethanol to give the corresponding substitution products 7-9. The cycloadditions of the nitrilimine 10, generated in situ from 5, to various olefinic dipolarophiles have been carried out. All reactions studied proceed with complete regioselectivity to give the 2-pyrazoline derivatives 11-13 and 16. Moreover, cycloaddition of 10 with enolates of various active methylene compounds afforded the pyrazole derivatives 22 and 27 in high yields. The cycloaddition regioselectivity is discussed in terms of the frontier orbital method.
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■ Stereostructure of Subulacine-N-oxide: A New Pyrrolizidine Alkaloid from Heliotropium subulatum
Abdul Malik* and Khalid Rahman
*H. E. J. Postgraduate Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan
Abstract
A new pyrrolizidine alkaloid, subulacine-N-oxide has been isolated from Heliotropium subulatum. Its structure and stereochemistry has been assigned as (1) on the basis of spectral studies including 2D-nmr.
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■ Studies on Reactive Intermediates. Part VI. Synthesis of Benzo[a]quinolizines via Methylketene Dimer
Mohsen Daneshtalab,* Ronald G. Micetich, and Sedighe Forghanifar
*SynPhar Laboratories Inc., 4290-91A Street, Edmonton, Alberta, T6E 5V2, Canada
Abstract
Reaction of methylketene dimer with isoquinoline in neat condition or refluxing ether resulted in the formation of 2-hydroxy-1,3-dimethyl-4-oxo-4H-benzo[a]quinolizine (VIII) in 55% yield. The reaction in acetic acid gave rise to 2-acetoxy-1,3-dimethyl-4-oxo-1,4-dihydro-11HBH-benzo[a]quinolizine (VI) and 2-acetoxy-1,3-dimethyl-4-oxo-4H-benzo[a]quinoIizine (VII) in 40% and 45% yields, respectively. Compound VI has been reported as one of the precursors of emetine type alkaloids.
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■ Tubastraine: Isolation and Structure of a Novel Alkaloid from the Stony Coral Tubastraea micrantha
Maktoob Alam,* Radhika Sanduja, and Gerard M. Wellington
*Department of Medicinal Chemistry and Pharmacognosy, University of Houston, Houston, Texas 77004, U.S.A.
Abstract
The non-symbiotic marine coral Tubastraea micrantha was found t o contain a novel alkaloid along with a previously known sesterterpene. The structures of the isolated metabolites were determined by spectroscopic methods.
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■ Isolation and Structural Studies on the Alkaloids of Alstonia macrophylla
Atta-ur-Rahman,* Muhammad Munawer Qureshi, Anjun Muzaffar, and Kuruneruge Tuley Dayanada de Silva*
*H. E. J. Postgraduate Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan
Abstract
A new oxindole alkaloid, 16-hydroxy-Nb-demethylalstophylline oxindole (I) has been isolated from the leaves of Alstonia macrophylla. Its structure has been determined by modern spectroscopic studies, particularly by NOE difference, COSY 45° and DEPT enperiments. Na-Methyl-1,2-dihydrostrictamine (II) has also been isolated from this new source.
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■ Preparation of Pyrazolo[1,5-a]pyridine and [1,2,4]Triazolo[1,5-a]pyridine Derivatives from 1,6-Diaminopyridine-2-thiones
Pedro Molina,* Alberto Tárraga, and Concepción Garcia
*Departmento de Química Orgánica, Facultad de Ciencias, Universidad de Murcia, 30071 Murcia, Spain
Abstract
The 1,6-diaminopyridine-2-thiones (1a and 1b)react with α-halocarbonyl compounds to give the pyrido [2,1-b][1,3,4]thiadiaziniumsalts (2) which undergo base-catalyzed ring-contraction to give the pyrazolo[1,5-a]pyridines (3) or (4). The reactions of the N-aminoheterocycles (1a and 1b) with nitriles lead directly to [1,2,4] triazolo-[1,5-a]pyridines (5).
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■ Practical Synthesis of Unnatural (+)-Physostigmine and Carbamate Analogues
Qian-Sheng Yu and Arnold Brossi
*Medical Chemistry Section, Laboratory of Chemistry, NIDDK, National Institute of Health, Bethesda, MD 20892, U.S.A.
Abstract
Details of a synthesis of unnatural (+)-physostigmine (5) prepared from urea 1 via (+)- eseroline (4) are given. Preparation of (+)-octylcarbamate 6, (+)-benzylcarbamate 7, (+)-phenylcarbamate 8 and (+)-N-methylphysostigmine (9) from (+)-eseroline (4) is also described.
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■ Hofmann Elimination with Diazomethane on Quaternary Benzyltetrahydroisoquinoline Related Alkaloids
Sheng-Teh Lu* and Ian-Lih Tsai
*School of Pharmacy, Kaohsiung Medical College, 100 Shih Chuen 1st Rd., Kaohsiung 80708, Taiwan, R.O.C.
Abstract
The investigation have been made to the reaction of a large excess of diazomethane on the quaternary henzyltetrahydroisoquinoline related alkaloids, aporphines, benzyltetrahydroisoquinolines, pavines and protopine. From the structural elucidation of the reaction products, it has been found that the first and second Hofmann elimination proceeded.
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■ Synthesis of 3-Substituted 3,4-Dihydropyrimidines: N-Alkoxycarbonylation with Trichloromethyl Chloroformate and Alcohols
Hidetsura Cho,* Akira Mizuno, Keiyuu Shima, Masaru Ueda, Yumi Takeuchi, Mikiko Hamaguchi, and Nobuaki Taniguchi
*The Institute of Food Chemistry, 1-1-1, Wakayamadai, Shimamotocho, Mishimagun, Osaka 618-0024, Japan
Abstract
N-Alkoxycarbonylation reactions of dihydropyrimidines with trichloromethyl chloroformate (phosgene dimer) and an alcohol were carried out in order to obtain the dihydropyrimidines with a complicated alkyl qroup or an alkyl group containing a nitrogen atom. Especially, the synthetically difficult problem of the unstable N-substituted dihydropyrimidines containing a nitrogen atom in an ester group was overcome by the method II: 0.5-1.2 mol equiv. of phosgene dimer, 1.0-6.0 equiv. of tertiary aminoalcohol, and 6 equiv. of Et3N in THF at -23°C-r.t.
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■ Synthesis of (±)-3-(1’,1’-Dimethylallyl)decursinol and 3-(1’-1’-Dimethylallyl)xanthyletin
Rosario Hernández Galán, Guillermo M. Massanet, Enrique Pando, Francisco Rodríguez Luis, and Javier Salvá
*Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Cádiz, Apartado 40, Puerto Real (Cádiz), Spain
Abstract
(±)-3-(1’,1’-Dimethylallyl)decursinol (1) and 3-(1’,1’-dimethylallyl)xanthyletin (2) were synthesized from umbelliferone (3) in each 6.9% overall yield.
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■ Scutellone C and F, Two New Neoclerodane Type Diterpenoids from Scutellaria rivularis
Yun-Lian Lin and Yueh-Hsiung Kuo*
*Department of Chemistry, National Taiwan University, Roosevelt Road Section 4, Taipei 106, Taiwan, R.O.C.
Abstract
Two new neoclerodane type diterpenoids, scutellone C and F, had been iaolated from aerial parts of Scutellaria rivularis Wall.. Their structures were elucidated by spectral and chemical evidence.
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■ Benzomorphan Related Compounds. XXIII. A New Synthesis of 7,8-Benzomorphans
Mario Rubiralta, Anna Diez, and Joan Bosch*
*Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Av. de Joan XXIII, s/n, 08028 Barcelona, Spain
Abstract
A new synthesis of 7,8-benzomorphans based on the acid catalyzed cyclization af 4-benzyl-2-cyanopiperidines is described.
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■ Addition of Stabilized Carbon Nucleophiles to N-Alkylpyridinium Salts. Applications to Alkaloids Synthesis
M. -Lluïsa Bennasar, Rodolfo Lavilla, Mercedes Alvarez, and Joan Bosch*
*Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Av. de Joan XXIII, s/n, 08028 Barcelona, Spain
Abstract
The application to alkaloid synthesis of the addition of stabilized carbon nucleophiles to N-alkylpyridinium salts is reviewed.