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. 63, No. 3, 2004
Published online: 16th January, 2004
■ Dodecasubstituted Porphyrins — An Easily Accessible Type of Dendritic Porphyrins with Tunable Properties
Claudia Ryppa and Mathias O. Senge*
*Institut für Chemie, Universität Potsdam, Karl-Liebknecht-Strasse 24-25, D-14476 Golm, Germany
Abstract
Dodecasubstituted dendritic porphyrins with nonplanar macrocycles were synthesized by a convergent approach via Lindsey condensation reactions in good yields.
Published online: 19th January, 2004
■ Acylated Peonidin 3-Rutinoside-5-glucosides from Commercial Petunia Cultivars with Pink Flowers
Fumi Tatsuzawa, Yukiko Toya, Hitoshi Watanabe, Yuji Hirayama, Koichi Shinoda, Ritsuko Hara, Hiroko Seki, and Toshio Ando*
*Faculty of Horticulture, Chiba University, 648 Matsudo, Matsudo City, Chiba 271-8510, Japan
Abstract
Two new acylated peonidin glycosides and three known acylated or non-acylated peonidin glycosides were identified in the flowers of 17 commercial pink petunias: peonidin 3-O-[6-O-(4-O-(4-O-(6-O-(trans-caffeoyl)-β-D-glucopyranosyl)-trans-p-coumaroyl)-α-L-rhamnopyranosyl)-β-D-glucopyranoside]-5-O-[β-D-glucopyranoside], peonidin 3-O-[6-O-(4-O-(4-O-(β-D-glucopyranosyl)- trans-p-coumaroyl)-α-L-rhamnopyranosyl)-β-D-glucopyranoside]-5-O-[β-D- glucopyranoside], peonidin 3-p-coumaroylrutinoside-5-glucoside, peonidin 3-caffeoylrutinoside-5-glucoside, and peonidin 3-rutinoside-5-glucoside.
Published online: 9th January, 2004
■ Synthesis and Spectroscopic Differentiation of 2- and 4-Alkoxythiotetronic Acids
Gautham Shenoy, Pilho Kim, Michael Goodwin, Quynh-Anh Nguyen, Clifton E. Barry, 3rd, and Cynthia S. Dowd*
*Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852, U.S.A.
Abstract
O-Alkylation of thiotetronic acids gives a mixture of 2- and 4-position enol ether products. Comparison of the physical data revealed that UV spectroscopy was the most reliable method of distinguishing between these related ethers. We have determined that 4-position ethers have a distinct absorption between 235-240 nm, while 2-position ethers have two absorbance peaks, one between 205-220 nm and the other between 305-310 nm. This report describes the synthesis and unambiguous characterization of 2- and 4-methoxy-3,5-dimethylthiotetronic acids. The UV absorption properties of several other pairs of thiotetronic acid ethers confirm that these differences are general features that provide a simple method for distinguishing between 2- and 4-substituted isomers.
Published online: 16th January, 2004
■ Synthesis and Cytotoxic Evaluation of Certain Tricyclic Benzo[g]quinolin-4(1H)-one and Benzo[g]quinoline-4,9,10-trione Derivatives
Shu-Lin Hsu, Yeh-Long Chen, and Cherng-Chyi Tzeng*
*Faculty of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City, Taiwan, R.O.C.
Abstract
The present report describes the synthesis and evaluation of tricyclic benzo[g]quinoline-4(1H)-one derivatives (CAB type) in which an additional aromatic ring is linearly fused on the antibacterial quinolone-3-carboxylic acid to maintain a free carboxylic acid (increase water-solubility) and a coplanar tricyclic DNA-intercalating chromophore (improve antitumor activity). 1H-Benzo[g]quinoline-4,5,10-trione, 1-methyl-1H-benzo[g]quinoline-4,5,10-trione, and ethyl 1-methylbenzo[g]quinoline-4,5,10-trione-3-carboxylate exhibited significant cytotoxicity against all 60 cancer cells with mean GI50 values of 5.92, 7.75, and 2.52 μM respectively while 1-methylbenzo[g]quinoline-4,5,10-trione-3-carboxylic acid and 5-hydroxy-10-methoxy-1-methylbenzo[g]quinolin-4(1H)-one- 3-carboxylic acid were inactive, indicated free carboxylic acid at C-3 position is unfavorable. The results have also implied the importance of carbonyl moieties at C-5 and C-10 due to the inactiveness of reduced products, ethyl 5-hydroxy-10-methoxy-1-methylbenzo[g]quinolin-4(1H)-one-3-carboxylate and ethyl 10-benzyloxy-5-hydroxybenzo[g]quinolin-4(1H)-one-3-carboxylate.
Published online: 9th January, 2004
■ Synthetic Studies on Azaspiracid, a Novel Shellfish Poison: Attempts to Construct the ABCD Ring System
Yuichi Ishikawa and Shigeru Nishiyama*
*Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522, Japan
Abstract
Synthesis of the ABCD ring system of azaspiracid (1) was attempted. Construction of the highly substituted tetrahydrofuran (9) via the Pd(0)-mediated cyclization, followed by spirocyclization afforded trispiro-ring (28), carrying an unnatural ring-junctions. The BCD ring system of 1 was successfully produced by using the bridge of a sulfur atom between the B and C ring to control the spiroacetal center of the C13 position. The stereostructures were unambiguously determined by the NOE experiments.
Published online: 16th January, 2004
■ Synthesis and Photochromic Properties of Methoxy Substituted 2,2-Diaryl-2H-naphtho[1,2-b]pyrans
Christopher D. Gabbutt, John D. Hepworth, B. Mark Heron,* David A. Thomas, Colin Kilner, and Steven M. Partington
*Department of Colour Chemistry, The University of Leeds, Leeds, LS2 9JT, U.K.
Abstract
A series of methoxy-substituted 2,2-di(4-methoxyphenyl)-2H-naphtho[1,2-b]pyrans has been synthesised from 3-alkoxycarbonyl-1-naphthols and 1,1-di(4-methoxyphenyl)prop-2-yn-1-ol. The influence of the methoxy group on the wavelength of maximum absorption and the stability of the ring-opened naphthopyrans is discussed.
Published online: 19th January, 2004
■ Green Chemistry Approaches to the Synthesis of 5-Arylidenethiobarbituric Acids by a Condensation Reactions between Aromatic Aldehydes and Thiobarbituric Acid: Comparison of Water, Microwave Irradiation, and Grinding
Jun Lu,* Yingying Li, Yinjuan Bai, and Min Tian
*Department of Chemistry, Northwest University, Xi'an, Shaan'xi 710069, China
Abstract
A general and practical green chemistry route to the synthesis of 5-arylidenethiobarbituric acids is described from aromatic aldehydes and thiobarbituric acid under three different sets of reaction conditions: water without catalyst conditions, microwave irradiation, and grinding method using NH4OAc as a catalyst at room temperature.
Published online: 26th December, 2003
■ Reaction of [1,4]Benzodioxinopyridazines with Sodium Methoxide and Amines
Etsuo Oishi,* Chitose Sugiyama, Ken-ichi Iwamoto, and Ikuo Kato
*Division of Environmental Health Sciences, Graduate of School of Nutritional & Environmental Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan
Abstract
The reaction of 1-chloro (3), 1-methylsulfonyl (7) [1,4]benzodioxino[2,3-d]pyridazine and 4-chloro[1,4]benzodioxino[2,3-c]pyridazine (4) with sodium methoxide afforded dioxin ring-opened pyridazines (14 — 16) and ring-cyclized pyridazines (9, 10), while their reaction with amines [n-butylamine (8a), cyclohexylamine (8b), morpholine (8c), piperidine (8d), pyrrolidine (8e), hydrazine (8f) and aniline (8g)] afforded 1-substituted [1,4]benzodioxino[2,3-d]pyridazines (18), 4-substituted [1,4]benzodioxino[2,3-c]pyridazines (19) and/or 2-hydroxyphenoxypyridazines (20 — 22).
Published online: 16th January, 2004
■ Synthesis of 5-Substituted Ethyl 3-Oxo-2H-pyrazolo[4,3-c]pyridine-7-carboxylates
David Bevk, Renata Jakse, Amalija Colobic, Ljubo Golic, Anton Meden, Jurij Svete,* and Branko Stanovnik*
*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, SI-1000 Ljubljana, Slovenia
Abstract
Ethyl (2E)-3-dimethylamino-2-[(4Z)-4-dimethylaminomethylidene-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl]propenoate (3) was transformed with N-nucleophiles into ethyl 3-oxo-2-phenyl-3,5-dihydro-2H-pyrazolo[4,3—c]pyridine-7-carboxylates (6, 7, 9, 12, and 14).
Published online: 19th January, 2004
■ Synthesis of Aromatic Ring Fused Pyrrole Derivatives by Palladium-catalyzed Annulation of o-Iodoarylamines with Allyl Acetate
Chang Sung Hong, Jae Yong Seo, Eul Kgun Yum,* and Nack-Do Sung
*Department of Chemistry, Chungnam National University, Yusung, Daejon 305-764, Korea
Abstract
Indoles, azaindoles, and pyrroloquinolines were obtained by palladium-catalyzed annulation of o-iodoarylamines with allyl acetate under 5 mol % Pd(OAc)2, 1 equiv. LiCl, 3 equiv. K2CO3 , and 2 equiv. allyl acetate in DMF at 120°C.
Published online: 9th January, 2004
■ Leptosins O-S, Cytotoxic Metabolites of a Strain of Leptosphaeria Sp. Isolated from a Marine Alga
Takeshi Yamada, Chika Iwamoto, Naoko Yamagaki, Takako Yamanouchi, Katsuhiko Minoura, Sanji Hagishita, and Atsushi Numata*
*Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
Abstract
Leptosins O (1), P (2), Q (3), R (4) and S (5) have been isolated from a strain of Leptosphaeria sp. originally separated from the marine alga Sargassum tortile. Their absolute stereostructures have been elucidated on the basis of spectroscopic analyses of their acetate derivatives (6—10) using various 1D and 2D NMR techniques and some chemical transformations. The NMR and NOE spectral analyses of 6—10 revealed that they exist in a single conformer of B type in CDCl3. Among these metabolites, leptosins O (1) and P (2) exhibited significant cytotoxicity against cultured P388 cells
Published online: 16th January, 2004
■ Syntheses of 1,2,3,4,6,7,12,12b-Octahydroindolo[2,3-a]quinolizine and Harmicine Using a Chiral 1-Allyl-1,2,3,4-tetrahydro-β-carboline as the Starting Material
Takashi Itoh, Michiko Miyazaki, Kazuhiro Nagata, Shigeru Nakamura, and Akio Ohsawa*
*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Abstract
Total syntheses of (S)-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine and (S)-harmicine were carried out using chiral 1-allyl-1,2,3,4-tetrahydro-β-carboline as the starting material.
Published online: 9th January, 2004
■ Density Functional Theory Study of the Preferred Conformation of Geissoschizine
Juriffah Ariffin, Hiromitsu Takayama, Mariko Kitajima, Norio Aimi,* and Chikara Kaneko
*Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
Density functional theory (DFT) study of the hitherto proposed structures of geissoschizine (1) has proved that the structure (1a) having hydrogen bond between the enol hydroxyl and Nb functions with a trans-quinolizidine-type C/D ring and twistboat D ring (proposed by van Tamelen and Wright) is the most stable one. A strong contribution of the zwitterionic species (1a') to 1a is suggested together with the reasons why 1a' was not found as a local minimum. Calculations of 1H- and 13C- NMR chemical shifts based on this structure also support its structure.
Published online: 16th January, 2004
■ Synthesis and Characterization of Potential Photolabeling Probes for Studying the Antiviral Mechanisms of EICAR
Qiongyou Wu, Jinqiao Wan, Yi Xia, Jiehua Zhou, Fanqi Qu, and Ling Peng*
*AFMB CNRS UMR 6098, Département de Chimie, Université Aix-Marseille II, 163, avenue de Luminy, 13288 Marseille, France
Abstract
The designed photolabeling probes: 5-diazonium-1-β-D-ribofuranosyl-1H-imidazole-4-carboxamide (1) and 5-azido-1-β-D-ribofuranosyl-1H-imidazole-4-carboxamide (2) were synthesized via a short and convenient synthetic route, namely by diazotizing AICAR and subsequently performing substitution with NaN3. Although 1 was not stable even at low temperatures, 2 showed a rapid and clean photochemical reaction, which suggests that it may be a valuable tool for use in photolabeling studies.
Published online: 19th January, 2004
■ Diastereoselective Synthesis of Substituted 2-Phenyltetrahydropyrans as Useful Precursors of Aryl C-Glycosides via Selenoetherification
Michelangelo Gruttadauria,* Carmela Aprile, Paolo Lo Meo, Serena Riela, and Renato Noto
*Department of Organic Chemistry "E. Paternò", University of Palermo, Viale delle Scienze, Parco d'Orleans II, 90128 Palermo, Italy
Abstract
The cyclization of several substituted 5-phenyl-pent-4-en-1-ols with selenium electrophiles along some mechanistic considerations is discussed. In particular, an efficient diastereoselective synthesis of a 2,3,5,6-tetrasubstitued tetrahydropyran is reported. These findings open an interesting approach: the use of chiral selenium electrophiles for cyclization of chiral substrates. The cyclized products are useful starting material for the synthesis of D- or L-aryl C-glycosides.
Published online: 23rd January, 2004
■ Quassinoid Xylosides, Javanicosides G and H, from Seeds of Brucea javanica
Ik Hwi Kim, Yukio Hitotsuyanagi, and Koichi Takeya*
*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Abstract
Two new quassinoid xylosides, javanicosides G and H, were isolated from the seeds of Brucea javanica (L.) Merr. (Simaroubaceae). Their structures were elucidated by the analysis of spectral data and chemical evidence.
Published online: 16th January, 2004
■ Practical Synthesis of DQ-113, a New Quinolone Antibacterial Agent, by Using the Intramolecular Horner-Wadsworth-Emmons Reaction
Hiroaki Inagaki, Toshiyuki Takeda, Rie N. Miyauchi, Katsuhiro Kawakami, Hisashi Takahashi, and Makoto Takemura*
*Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd., 16-13, Kita-Kasai 1-Chome, Edsogawa-ku, Tokyo 134-8630, Japan
Abstract
A practical route was developed for synthesizing the C-7 substituent of DQ-113 (6, 5-amino-7-[(3S,4R)-4-(1-aminocycloprop-1-yl)-3-fluoropyrrolidin-1-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropan-1-yl]-1,4-dihydro- 8-methyl-4-oxoquinolin-3-carboxylic acid), a new quinolone antibacterial agent for serious infections caused by Gram-positive pathogens. The key step was the intramolecular Horner-Wadsworth-Emmons reaction. In addition, the yield of the final aromatic nucleophilic substitution reaction was improved.
Published online: 16th January, 2004
■ A Convenient Synthesis of Trifluoromethylpyridazines from 3-Hydrazono-1,1,1-trifluoroalkan-2-ones
Yasuhiro Kamitori* and Tomoko Sekiyama
*Department of Chemical Science and Engineering, Faculty of Engineering, Kobe University, Kobe 657-8501, Japan
Abstract
3-Hydrazono-1,1,1-trifluoroalkan-2-ones readily obtained from aldehyde dialkylhydrazones reacted with acetylacetone to afford the corresponding 4-acetyl-3-methyl-5-trifluoromethylpyrizazines in good yields. The reaction with ethyl acetoacetate also gave the corresponding pyridazines. These reactions proceeded successfully in the absence of any catalyst.