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. 75, No. 5, 2008
Published online: 29th January, 2008
■ Synthetic Philosophy: A Study Directed toward Creation of an Ideal Synthetic Method and Its Application for Preventing Global Warming by Combating Desertification
Masanori Somei
*Faculty of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan
Abstract
This review reports how the author has been realizing his synthetic philosophy and five dreams as his life work. The philosophy consists of such three elements as originality rate, intellectual property factor, and application potential factor. On the basis of these elements, an ideal and an efficient synthesis are defined. In the study for the total synthesis of ergot alkaloids, the first concrete example of an approximately ideal synthesis was demonstrated. Further examples are shown relying on the chemistry of 1-hydroxyindoles. A lot of intellectual properties created by the author are successfully condensed to provide promising lead compounds meeting for the respective dreams of developing five drugs 1) for making desert green and food increase in production, 2) for cardiovascular system disease, 3) for dementia, 4) for lifestyle-related disease (osteoporosis, etc.), and 5) for cancer and virus. With potent promoters of plant’s root growth in hand, the first dream is going now successfully. Preliminary experiments combating desertification at Gobi desert in Inner Mongolia are reported in detail, aiming for preventing global warming.
Published online: 5th February, 2008
■ Efficient Synthesis of 2-Mono- and 2,3-Disubstituted Indoles via Palladium-Catalyzed Oxidation of Amino Alcohols
Yutaka Aoyagi, Masahiro Shishikura, Toshihiko Mizusaki, Takashi Komine, Tokuji Yoshinaga, Haruko Inaba, Akihiro Ohta,* and Koichi Takeya*
*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
Efficient synthesis of 2-mono- and 2,3-disubstituted indoles has been accomplished via palladium-catalyzed oxidation of aminoalcohols.
Published online: 8th February, 2008
■ Synthesis and DNA Cleavage Activity of 4,2’:4’,4’’:2’’,4’’’-Quaterthiazoles
Hideaki Sasaki
*Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Nishi-ku, Kobe 651-2113, Japan
Abstract
A series of 4,2’:4’,4”:2”,4’’’-quaterthiazole derivatives (2) were readily synthesized via a novel five-steps reaction. The key reaction involved the condensation of 1,4-dibromobutane-2,3-dione with two equimolar amounts of 2- (Boc-protected aminoalkyl)-thiazole-4-carbothioamide. The obtained 2,2’’’-bis-(3,6-diazahexyl)- and 2,2’’’-bis(3,6,9-triazanonyl)-4,2’:4’,4”:2”,4’’’-quaterthiazole (2b and 2c) exhibited significant affinity for double-stranded DNA, such as calf thymus DNA, as well as marked DNA cleavage activity in the presence of Co(II) ions under physiological conditions. Furthermore, the formation of a Co(II)-complex with 2b and 2c was found to be necessary for the DNA cleavage activity.
Published online: 18th January, 2008
■ Structural and Conformational Studies on Two Diastereomeric Dihydroisoxazolyl Cyclopropane Derivatives
Fiorella Meneghetti* and Roberto Artali
*Institute of Pharmaceutical and Tossicological Chemistry “P. Pratesi”, Via Mangiagalli 25, I-20133 Milano, Italy
Abstract
The molecular structures of 2-(3’-bromo-4’,5’-dihydro-isoxazol-5’-yl)-1-tert-butoxycarbonylaminocyclopropanecarboxylic acid (±)-10a and 1-amino-2-(3’-hydroxy-4’,5’-diydro-isoxazol-5’-yl)cyclopropanecarboxylic acid (±)-11b were determined by single crystal X-ray diffraction method. The geometrical features and the intermolecular interactions of the two diastereoisomers have been compared evidencing a different conformation of the dihydroisoxazole ring: in (±)-10a is almost planar, while in (±)-11 adopts an envelope shape. Intermolecular hydrogen bonds of OH…O and NH…O type in (±)-10a determine the formation of a three-dimensional network, whereas in (±)-11b polimeric chains due to NH…O interactions are obtained. These compounds are key intermediates of conformationally constrained glutamic acid homologues and the opposite stereochemistry of C(3) leads to different pharmacophoric distances, important for the ligand-receptor interaction. The results of the X-ray molecular structures have been complemented by theoretical calculations.
Published online: 25th January, 2008
■ Synthesis and Study of Reactivity of Pyrrolo[3,2-e][1,2,4]triazine System
Jakub Styskala,* Jan Slouka, and Petr Cankar
*Department of Organic Chemistry, Palacky University, Trida Svobody 8, 77146 Olomouc, Czech Republic
Abstract
The corresponding 2-arylhydrazones 5 were obtained by coupling of diazonium salts with diethyl (3-methyl-1H-pyrrole)-2,4-dicarbamate 4. These ones were cyclized in a alkaline medium to ethyl (2-aryl-5-methyl-3- oxo-2,3-dihydro-7H-pyrrolo[3,2-e][1,2,4]triazin-6-yl)carbamates 6 and tested for their stability. The starting carbamate 4 was prepared by a multistep synthesis from diethyl 3-methyl-1H-pyrrole-2,4-dicarboxylate 1.
Published online: 22nd January, 2008
■ The Subtle Co-catalytic Intervention of Benzophenone in Radical Cation Mediated Cyclization — An Improved Synthesis of 2-(3’,4’-Dimethoxyphenyl)indoline
Noel Francis Thomas,* Chin-Hui Kee, Azhar Ariffin, Khalijah Awang, Jean-Frédéric Faizal Weber, Chuan-Gee Lim, Mat Ropi Mukhtar, and A. Hamid A. Hadi
*Department of Chemistry, University of Malaya, Pantai Valley, 50603 Kuala Lumpur, Malaysia
Abstract
The addition of benzophenone to a FeCl3/CH2Cl2 mixture in the presence of 3’,4’-dimethoxy-2-acetamidostilbene 17 unexpectedly leads to a dramatic improvement in yield of the indoline 20 from 38% (previously reported by us) to 75.4%, after careful examination of a variety of reaction conditions. A catalytic cycle has been proposed that involves not only stilbene radical cations but also Fe2+ promoted benzophenone ketyl radical formation which enhances cyclisation, suppresses dimerization and accounts for the virtually quantitative recovery of the benzophenone.
Published online: 1st February, 2008
■ Structures of New Triterpene Glycosides, Malbrancheosides A - D, from Malbranchea filamentosa
Daigo Wakana, Tomoo Hosoe, Takeshi Itabashi, Hideaki Okada, Kazutaka Fukushima, and Ken-ichi Kawai*
*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
In the course of searching for new biologically active metabolites in Malbranchea filamentosa, four new triterpene glycosides, malbrancheosides A (1) - D (4), were isolated. The structures of 1- 4 were confirmed by the chemical and spectro¬scopic investigation. Malbrancheosides A (1) - D (4) are the first example of triterpenoidal glycosides having D-glucosamine derivatives from the fungal sources.
Published online: 18th January, 2008
■ Synthesis of Functionalized β-Enamino Compounds by Carbon-Fragment Transfer Reaction of C(2)-Substituted Imidazolidines with Amines
Yongbin Zhang, Donghong Li, Guofu Zhou, Chizhong Xia, and Wei Guo*
*School of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China
Abstract
The substituted imidazolidines (2, 3, 5) and a ring-opening product, N,N,N’2-trisubstituted 2-methyl-ethylenediamines (4), derived from addition of the carbon anions to 1-tosyl-3,4-dimethylimidazolinium iodide (1), were utilized to transfer substituted one-carbon units to various amines to yield a series of functionalized β-enamino compounds.
Published online: 25th January, 2008
■ Synthesis of Nitrogen Heterocycles by Intramolecular Cyclization of Alkenyl N-Acylaminophthalimides Using Phenyliodine(III) Bis(trifluoroacetate) (PIFA)
Masato Tsukamoto, Kousuke Murata, Takeshi Sakamoto, Setsuo Saito,* and Yasuo Kikugawa*
*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
Abstract
PIFA-mediated intramolecular cyclization of alkenyl N-acylaminophthalimides leads to the formation of a new C-N bond via an N-acyl-N-phthalimidonitrenium ion intermediate. The reaction pathway also results in the introduction of an oxygen function into the molecule giving added versatility to this single step procedure.
Published online: 8th February, 2008
■ Studies with Condensed Aminothiophenes: Microwave Assisted Cycloaddition Reactions of Thieno[3,4-d]pyridazinone and Thieno[3,4-c]quinolinone
Saleh Mohammed Al-Mousawi,* Morsy Ahmed EL-Apasery, and Mohamed Hilmy Elnagdi
*Department of Chemistry, Faculty of Science, University of Kuwait, Safat 13060, P.O. Box 12613, Kuwait
Abstract
The arylformazane (2) was produced via coupling the α-oxoarylhydrazones (1) with aromatic diazonium salts. These formazane condensed readily with ethyl cyanoacetate to yield arylazopyridazinones (4) that reacted with sulphur in the presence of piperidine to yield the aminoazothienopyridazinone (5), the latter was reacted with electron poor olefins and acetylenes to yield aminoazophthalazines (8). Compound (8) was reacted with dimethylformamide dimethylacetal to yield amidine (9). Similarly aminothienoquinolinone (17) was reacted with electron poor olefins and acetylenes to yield aminophthalazines (20, 22a,b).
Published online: 8th February, 2008
■ Synthesis and Biological Evaluations of New Pyrrolo[2,3-b]pyrimidine as SDI Analogs
Jérôme Guillard and Marie-Claude Viaud-Massuard*
*EA 3857 Laboratoire de Synthèse et Physicochimie, Organique et Thérapeutique, University of Tours, 31 Avenue de Monge, 37200 Tours, France
Abstract
The synthesis of new pyrrolo[2,3-d]pyrimidines variously substituted on the N-1 and C-2 atoms are described. Access to these compounds, which have modest activity compared with the first inhibitor SDI, involves, as the key step, the formation of a pyrrolopyrimidine skeleton from the 5-amino-2-(methoxymethyl)pyrimidine.
Published online: 22nd January, 2008
■ Two Indolotryptanthrin Alkaloids from Cephalantheropsis gracilis
Yao-Ting Wu,* Yu-Lin Hsu, and Pei-Lin Wu*
*Department of Chemistry, National Cheng Kung University, Tainan, 701, Taiwan, R.O.C.
Abstract
Two alkaloids of indolotryptanthrins, cephathrindole A (1) and B (2), were isolated from Cephalantheropsis gracilis. The structure of cephathrindole A was confirmed by X-ray crystallography whereas cephathrindole B was ascertained by spectroscopic analysis (1D 1H- and 13C-NMR as well as 2D COSY, HMQC, HMBC, and NOESY).
Published online: 18th January, 2008
■ Diels-Alder Reactions of a Styrene-Isocyanate: Unexpected Formation of a Pyridinone and Uracil
Gregory A. Gfesser,* David Whittern, Marlon D. Cowart, and Ramin Faghih
*Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA
Abstract
During the preparation of 6-bromoisoquinolinone, a novel and unexpected reaction occurred to form a pyridinone and a pyrimidine-2,4-dione. We propose a [4+2] Diels-Alder dimerization of an intermediate styrene-isocyanate to explain the observed products.
Published online: 25th January, 2008
■ MoO3/Al2O3: An Efficient and Reusable Heterogeneous Catalyst for Solvent-Free Synthesis of Coumarins via Pechmann Condensation
Sweety Singhal, Suman L. Jain, and Bir Sain*
*Chemical and Biotechnology Division, Indian Institute of Petroleum, Dehradun-248005, India
Abstract
16 wt % alumina supported MoO3 has been found to be an efficient catalyst for the synthesis of various substituted coumarins via Pechmann condensation. This method offers several advantages like high yields, facile recovery and reusability of the catalyst without loss in activity, nearly neutral and solvent free condition.
Published online: 5th February, 2008
■ Applicability of Methyl 2,3,4-Tri-O-benzoyl-1-methanesulfonyl-α-D-glucopyranuronate as a Novel Quaternary Glucuronyl Reagent for Tertiary Amines
Ichiro Araya* and Hiroyuki Akita
*Reseach Center, Kyorin Pharmaceutical Co., Ltd., 1848 Nogi, Nogi-mcahi, Shimotsuga-gun, Tochigi, 329-0114, Japan
Abstract
Applicability of a methyl 2,3,4-tri-O-benzoyl-1-methanesulfonyl-α-D-glucopyranuronate 3 as a novel quaternary glucuronyl reagent was investigated. The reaction of 3 with an aromatic tertiary amines such as pyridine derivatives or imidazole derivatives proceeded to give quaternary N-glucuronides in a moderate yields, but the reaction of 3 with an aliphatic tertiary amine did not occur. In case of the reaction of 3 with nicotine which has aromatic and aliphatic tertiary amines in the molecule, the reaction proceeded selectively on the pyridine ring to give the corresponding N-glucuronide. The present reagent was considered to be useful for the formation of N-quaternary glucuronide from aromatic tertiary amines.
Published online: 5th February, 2008
■ Synthesis of 2,4-Disubstituted Isoquinolin-1(2H)-ones Based on Reactions of α-Substituted 2-Lithio-β-methoxystyrenes with Isocyanates
Kazuhiro Kobayashi,* Kazutaka Hayashi, Changeng Nam, Shuhei Fukamachi, and Hisatoshi Konishi
*Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
Abstract
An efficient method for the preparation of 2,4-disubstituted isoquinolin-1(2H)-ones is described. The reaction of α-substituted 2-lithio-β-methoxystyrenes, generated by treating α-substituted 2-bromo-β-methoxystyrenes with butyllithium, with isocyanates yields the corresponding α-substituted 2-(2-methoxyvinyl)benzamide derivatives, which in turn are transformed into 2,4-disubstituted isoquinolin-1(2H)-ones on treatment with a catalytic amount of concentrated hydriodic acid.
Published online: 22nd January, 2008
■ Unexpected Unique Behavior of Spiro-Isoquinolines with a Cyclohexadienone System in Attempted Dienone-Phenol Rearrangement
Hiroki Shigehisa and Toshio Honda*
*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Abstract
8’,9’-Dimethoxy-1’,5’,6’,10b’-tetrahydro-4H-spiro(cyclohexa-2,5- diene-1,2’-pyrrolo[2,1-a]isoquinoline)-3’,4-dione 2 with a basic skeleton of a natural product, annnosqualine, exhibited unique behavior in a dienone-phenol rearrangement. Treatment of 2 with trifluoroacetic acid gave a simple 1-benzylisoquinoline alkaloid, norarmepavine 4. Plausible reaction mechanism for the observed transformation is also described.
Published online: 8th February, 2008
■ ent-Sauchinone from Saururus chinensis
Lishu Wang, Daqing Zhao, Dongyan Cheng, and Yonghong Liu*
*Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China
Abstract
A new lignan ent-sauchinone (1) was isolated from Saururus chinensis. The structure has been established on the basis of spectral methods and confirmed by X-Ray crystallographic analysis.