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. 53, No. 9, 2000
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■ The First Total Synthesis of (R )-(-)-Pyridindolol K2 and Its Enantiomer
Naoko Kanekiyo, Tominari Choshi, Takeshi Kuwada, Eiichi Sugino, and Satoshi Hibino*
*Graduate School of Pharmacy and Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama, Hiroshima 729-0292, Japan
Abstract
The enantioselective first total synthesis of (R)-(-)-pyridindolol K2 (2) together with its enantiomer (2a) has been achieved in nine steps.
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■ Simple Syntheses of Indol-1-yl Glucosides
Fumio Yamada, Toshikatsu Hayashi, Koji Yamada, and Masanori Somei*
*Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan
Abstract
A lithium hydroxide promoted glucosidation of 1-hydroxyindoles with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide is newly developed. Applying this method, the first and simple syntheses of novel indol-1-yl glucosides were achieved.
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■ Towards the Synthesis of Scyphostatin
Mukund K. Gurjar* and Srinivas Hotha
*Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune 411 008, India
Abstract
Stereocontrolled synthesis of the substituted cyclohexenone segment
(2) of scyph-ostatin (1) is described starting from D-glucose.
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■ Studies on Pyrimidine-annulated Heterocycles: Synthesis and Dynamic Properties of [n](2,4)Pyridinophanes (n = 11, 9, 8, 6)
Hiroyuki Yamamoto, Hidekazu Takeda, and Makoto Nitta*
*Department of Chemistry, School of Science and Engineering, Materials Research Laboratory for Bioscience and Photonics, Waseda University, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
A new short synthesis of the 1,3-dimethyluracil-annulated [n](2,4)pyridinophane ring system (n = 11, 9, 8, 6) (5,7-polymethylene-substituted pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones) consists of allowing 6-amino-1,3-dimethyluracil to react with cyclic α,β-unsaturated ketones. Structural studies of the compounds prepared were based on spectroscopic measurements and theoretical calculations. The 1H and 13C NMR spectra at various temperatures showed dynamic behavior for the oligomethylene chain of [6](2,4)pyridinophane derivative (9d). The energy barriers ΔGc‡ of the bridge flipping is ca. 20 kcalmol-1 (Tc, 150 °C). The lower-energy process of the oligomethylene in 9d is the pseudorotation with ΔGc‡ being 10.1 kcalmol-1 (Tc, -30 °C). Two stable conformers of the hexamethylene bridge of annulated [6](2,4)pyridinophane (9d) were determined for the first time by low-temperature NMR spectroscopy and theoretical calculations. Furthermore, the first example of rearrangement observed in the dehydrogenation reaction of a 3,4-dihydro[5](2,4)pyridinophane derivative in the presence of DDQ suggested the large strain of the [5](2,4)pyridinophane ring system.
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■ Reactions of Thioquinanthrene with Disodium Salts of Glycols
Stanislaw Boryczka*
*Department of Organic Chemistry, Silesian School of Medicine, Jagiellonska Str. 4, 41-200 Sosnowiec, Poland
Abstract
Reactions of thioquinanthrene (1) with disodium salts of 1,3-propylene, l ,4-butylene and diethylene glycol in DMF at 70 °C followed by S-methylation of thiolate (2-A) in aqueous sodium hydroxide afforded 4-(ω-hydroxyalkoxy)- 3’-methylthio-3,4’-diquinolinyl sulfides (2). S-Methylation of 2-A performed dire-ctly in DMF solution provided three types of the products (2), (3) and (4) which yield depended on the type of the disodium salt of glycol reacted. Reaction of 1 with disodium salt of ethylene glycol in DMF at 70 °C gave 4-(2-hydroxyethoxy)- 3’-methylthio-3,4’-diquinolinyl sulfide (2d) in low yield. The same reaction carried out in DMSO afforded the quinolones (5) and (7) as dealkylated products.
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■ Reactions of a Stable Benzonitrile Oxide with Aminopyridines
Paolo Beltrame, Enzo Cadoni, Costantino Floris, Gioanna Gelli,* and Adolfo Lai
*Dipartimento di Scienze Chimiche, Università di Cagliari, S. P. Monserrato-Sestu km 0.700, I-09042 Monserrato, Italy
Abstract
Stable aryl nitrile oxide (1) and isomeric aminopyridines (2) undergo different reactions depending on both the isomer and the conditions. The nitrile oxide gives 1,3-cycloaddition to the 4-aminopyridine (2c) in its iminic form if acids are present to promote the formation of imine. In such a case, the stable products 3,5-dichloro-2,4,6-trimethyl-N’-(4-pyridinyloxy)benzene carboximidamide (3E) and (3Z) are observed, otherwise, 2c catalyzes the dimerization, with the loss of an oxygen atom, of 1, leading to 3,5-bis-(3,5-dichloro-2,4,6-trimethylphenyl)-1,2,4-oxadiazole (4) as the main product. A similar 1,3-cycloaddition is given by 2-aminopyridine (2a): the compounds (5R and 5S)-(±)-3-(3,5-dichloro-2,4,6-trimethylphenyl)-1-oxa-2,4,6-triazaspiro [4,5]-deca-2,7,9-triene (6) and (5R and 5S)-(±)-3-(3,5-dichloro-2,4,6-trimethylphenyl)-1-oxa-2,4,6-triazaspiro[4,5]-deca-3,7,9-triene (7) have been identified, although subsequent reactions give the stable products (NZ,N’Z)-3,5-dichloro-2,4,6-trimethyl-N-[2(1H)-pyridinylidene]-N’-(2-pyridinyloxy)benzene carboximidamide (8) and (NE,N’Z)-3,5-dichloro-2,4,6-trimethyl-N-[2(1H)-pyridinylidene]-N’-(2-pyridinyloxy)benzene carboximidamide (9); these reactions proceed even in the absence of acids with no dimerization of 1, but acids (pyridinium chloride) speed them up remarkably. Addition of 1 onto the 3-aminopyridine (2b) leads to N-hydroxybenzenecarboximidamides (12), as well as to small amounts of a benzamide (13), and the effect of the pyridinium chloride is negligible.
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■ Total Syntheses of Naamine A and Naamidine A, Marine Imidazole Alkaloids
Shunsaku Ohta,* Naoki Tsuno, Seikou Nakamura, Norio Taguchi, Masayuki Yamashita, Ikuo Kawasaki, and Mieko Fujieda
*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan
Abstract
The first total syntheses of naamine A (4) and naamidine A (5), marine imidazole alkaloids, were achieved through twelve and thirteen steps of reactions, respectively, starting from 1-methyl-2-phenylthio-1H-imidazole (17).
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■ Synthesis of 4(5)-(5’-Amino-5’-deoxy-α-L-arabinofuranosyl)imidazole and Its 5’-Derivatives Using Modified Mitsunobu Cyclization: Synthetic Studies toward Novel Histamine H3-Ligands
Lisa Araki, Shinya Harusawa, Hirokazu Suzuki, and Takushi Kurihara*
*Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
Abstract
The modified Mitsunobu cyclization of 4-(2’,3’,5’- tri-O-benzyl-L-arabinosyl)imidazole (11RS) using N,N,N’,N’-tetramethyl- azodicarboxamide and Bu3P followed by ethoxycarbonylation produced a mixture (α / β = 20 / 1) of ethyl 4-(2’,3’,5’-tri-O-benzyl-L-arabinofuranosyl)- imidazole-1-carboxylate (13). The compound (13) was converted into ethyl 4-(5’-deoxy-5’-phthaloylamino-L-arabinofuranosyl)imidazole-1-carboxylate (15), which was subsequently led to 4-(5’-amino-5’-deoxy-α-L- arabinofuranosyl)imidazole (2α). The 4(5)-{5-[N-(4-chlorophenyl)thio- ureido]-α-L-arabinofuranosyl}imidazole (18), 4(5)-{5-[N-(4-chlorophenyl)- ureido]-α-L-arabinofuranosyl}imidazole (19), and 1-cyano-2-methyl-3- {5-deoxy—1-[1H-imidazol-4(5)-yl]-α-L-arabinofuranosyl}guanidine (20) were efficiently synthesized from 2α.
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■ Dipyrrolo[1,2-a:1’,2’-c]quinazoline, a New Ring System of Biological Interest
Francesco Mingoia, Patrizia Diana, Paola Barraja, Antonino Lauria, and Anna Maria Almerico*
*Dipartimento Farmacochimico, Tossicologico e Biologico, Università degli Studi di Palermo , Via Archirafi 32, 90123 Palermo, Italy
Abstract
Dipyrrolo[1,2-a:1’,2’-c]quinazoline derivatives (10a-c) and (11b,c) were obtained in moderate to good yields by trifluoromethanesulfonic acid catalyzed decomposition of 2-(3-azidophenyl)-1-(1H-pyrrol-2-yl)pyrroles (8a-c), through cyclisation of the protosolvated intermediates arylnitrenium ions (9).
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■ Norditerpenoid and Diterpenoid Alkaloids from the Roots of Aconitum nasutum Fisch. ex Reichb.
Ali H. Meriçli, Filiz Meriçli, Haridutt K. Desai, Balawant S. Joshi, Quincy Teng, Kinkini Bhattacharyya, Gülay Melikoglu, Mustafa Küçükislamoglu, Ayhan Ulubelen, and S. William Pelletier*
*Institute for Natural Products Research, Department of Chemistry, University of Georgia, Athens, Georagia 30602-2556, U.S.A.
Abstract
Investigation of the alkaloidal constituents of the roots of Aconitum nasutum led to the isolation and identification of a new diterpenoid alkaloid designated as trabzonine (1). Three known norditerpenoid alkaloids, lappaconitine (2), lycoctonine (3) and gigac-tonine (4), and two known diterpenoid alkaloids pseudokobusine (5) and septa-tisine (6) were also isolated. The structures of 1 and 5 were estab-lished by detailed analyses of 1H and 13C NMR data. The structure and absolute stereochemistry of pseudokobusine (5) was determined by an X-Ray crystal structure determination.
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■ Structure and Reaction of 2,6-Bis(alkoxycarbonyl)-1-methyl-2H - and 4H -Selenopyranium Tetrafluoroborates
Eiji Honda, Tatsunori Iwamura, Shin-ichi Watanabe, and Tadashi Kataoka*
*Gifu Pharmaceutical University, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Abstract
The stereochemistry of the three isomers of 2,6-bis(ethoxycarbonyl)-1-
methylselenopyranium salts was discussed on the basis of their NMR spectral data and determined to be 4H-, trans-2H-, and cis-2H-selenopyranium salts (3a, trans-4a, and cis-4a). A mixture of selenopyranium salts (3b) and (4b) reacted with carbonyl compounds at the 4-position to give 4-methylidene-4H-selenopyranium salts (6-9), whereas the corresponding selenabenzene (5b) did not react with acetone. The reaction of 5b proceeded in the presence of BF3·Et2O to give selenonium salt (6) and demethylated product (10) in 65 and 33% yields, respectively.
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■ A Synthesis of 2,3,4,5-Tetrahydro-1H-3-benzazepines via Pummerer-Type Cyclization of N-(2-Arylethyl)-N-(2-phenylsulfinylethyl)formamides
Jun Toda, Tsuyoshi Ichikawa, Toshiaki Saitoh, Yoshie Horiguchi, and Takehiro Sano*
*Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan
Abstract
A construction of 2,3,4,5-tetrahydro-1H-3-benzazepine ring system (7) was achieved via Pummerer-type cyclization of N-(2-arylethyl)-N-2- (phenylsulfinylethyl)formamides (6). This route produced the benzazepines (10) and (11) in six steps starting from readily available 2-arylethylamines (2) and 2-chloroethyl phenyl sulfide.
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■ Two New Xanthyletin-Type Coumarins from Peucedanum Decursivum
Ling-Yi Kong, Nian-Huan Yao, and Masatake Niwa*
*Faculty of Pharmacy, Meijo University, Tempaku, Nagoya 468-8503, Japan
Abstract
Two new xanthyletin-type coumarins were isolated from the root of Peucedanum decursivum and the structures were established as 3′(S),4′(R)-biangeloyloxys-3′,4′-dihydroxanthyletin and 3′(S)-senecioyloxy-4′(R)-angeloyloxy-3′,4′-dihydroxanthyletin, respectively, by spectroscopic methods. The absolute configurations were deduced by chemical correlations with known compounds.
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■ 1-epi -Deacetylaconitine, a New Norditerpenoid Alkaloid from Aconitum nemorum
Xiaoyi Wei,* Haihui Xie, Meifang Liu, and Xuejun Ge
*South China Institute of Botany, the Chinese Academy of Sciences, Guangzhou 510650, China
Abstract
A new norditerpenoid alkaloid, 1-epi-deacetylaconitine (1), along with three known compounds, neoline, songorine and 12-epi-napelline, was isolated from the roots of Aconitum nemorum. The structure of the new compound was elucidated on the basis of 1D and 2D NMR, EIMS and FABMS experiments. The structure of 1-epi-deacetylaconitine is unusual because it is the only aconitine series norditerpenoid alkaloid in which the 1-methoxyl group exists in the β-configuration and an intramolecular hydrogen bond is present between the nitrogen atom and the hydrogen of 3α-hydroxyl group.
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■ Synthesis and Transformations of Alkyl 1,5-Bis(dimethylamino)-3-oxopenta-1,4-diene-2,4-dicarboxylates. A Simple Synthesis of Dialkyl 1-Substituted 4-Oxo-1,4-dihydropyridine-3,5-dicarboxy-lates
Silvo Zupancic, Jurij Svete,* and Branko Stanovnik*
*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, 1000 Ljubljana, Slovenia
Abstract
Dimethyl (2a) and diethyl 1 ,5-bis(dimethylamino)-3-oxo-penta-1,4-diene-2,4-dicarboxylate (2b), available in good yields from the corresponding dialkyl acetonedicarboxylates (1a, b) and N,N-dimethylformamide dimethyl acetal (DMFDMA), were used as reagents for a one-step preparation of 1-substituted 1,4-dihydropyridin-4-ones (3a-u). Thus, compounds (2) were treated with ammonia, hydrazines, and primary aliphatic, aromatic, or heterocyclic
amines to form dialkyl 1-substituted 4-oxo-1,4-dihydropyridine-3,5-dicarboxylates (3a-u).
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■ Macrocyclic Compounds: Synthesis of Various 6,15-Dithia-2,3,8,11,12,17,19,20-octaazatricyclo[14.2.1.17,16]eicosa-1,7(20),10,16(19)-tetraene-4,13-dione Derivatives Having Potential Antitumer Activity
Mohamed Abdel Hamid Ismail*
*Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain-Shams University, Cairo, Egypt
Abstract
Acylation, carbonylation, and oxalylation of the 4-hydrazono-2-thioxoimidazolidine (1a) with various acyl chlorides, N,N`-carbonyldiimidazole and oxalyl chloride, gave the corresponding 4-acylhydrazono derivatives (2a-c), N2,N2`-bis(imidazolidine-4-ylidine)carbazide (3) and oxalic acid N2,N 2`-bis[(imidazolidine-4-ylidine)hydrazide] (4), respectively. Alkylation of 2a prod-uced the 2-alkylthio derivatives (5a-f). Reactions of 1a-b with chloroacetyl chloride in DMAP and pyridine gave the titled macrocycles (7a-b). Reaction of 1a with chloroacetyl chloride in K2CO3 gave a mixture of 7a and 4-chloro-acetylhydrazono derivative (6). Acylation of 7a-b with acyl chlorides generated the tetraacyl-hetrophanes (8a-d). Compounds (5c) and (7a) displayed superior cytotoxic activity against Ehrlich ascites than Doxorubicin® medicament.
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■ Stereoselective Synthesis of (Z )-α-Phenoxymethylene-γ-butyrolactone and Its Sulfur Analogues from 2-Propynyloxy- or 2-Propynylthiobenzene
Fen-Tair Luo,* Sheng-Li Ko, Lijun Liu, and Hui Chen
*Institutue of Chemistry, Academia Sinica, Nankang, Taipei, Taiwan 11529, R.O.C.
Abstract
The preparations of (Z)-α-phenoxymethylene-γ-butyrolactone, α- phenoxymethyl-γ-butyrolactone, (Z)-α-phenylthiomethylene-γ-butyrolactone, and α-phenylthiomethyl-γ-butyrolactone derivatives from 2-propynyloxybenzene and 2-propynylthiobenzene were described.
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■ Six New O -Terpenoidal Coumarins, Excavacoumarins B-G from Clausena excavata
Hongping He, Yuemao Shen, Yineng He, Xiaosheng Yang, Guoying Zuo, and Xiaojiang Hao*
*Laboratory of Phytochemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650204, China
Abstract
Six new O-terpenoidal coumarins named excavacoumarins B-G (1-6) were isolated from the aerial part of Clausena excavata collected in Xishuangbanna, Yunnan.
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■ Addition Reaction of Cyclic Ethers to 1,1-Ethylene-1H -azulenium Ion
Mitsunori Oda,* Takuya Uchiyama, Takanori Kajioka, Tomomi Hashimoto, Ryuta Miyatake, and Shigeyasu Kuroda*
*Department of Applied Chemistry, Faculty of Engineering, Toyama University, Gofuku 3190, Toyama 930-8555, Japan
Abstract
The title cation (1) was found to react with some cyclic ethers in the presence of sodium acetate and acetic acid to give the products derived from nucleophilic addition of the ether oxygen atom at the three-membered ring methylene carbon of 1.