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. 55, No. 4, 2001
Published online:
■ On the Synthesis and Reactivity of 1-Benzyl-2-arylquinoline-4-thiones
Edmund J. Niedzinski, Matthew R. Lashley, and Michael H. Nantz*
*Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616-5295, U.S.A.
Abstract
A panel of 1-benzyl-2-aryl-4-quinolones was synthesized in three steps and converted to the corresponding 4-thione derivatives using Lawesson’s reagent. The representative vinylogous thioamide (5a) was alkylated to afford a novel series of quinolinium salts.
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■ A Convenient in situ Preparation of Triphenylbismuthane (Tropon-2-yl)imide: Reaction with Heterocumulenes and Activated Alcohols
Makoto Nitta* and Yuhki Mitsumoto
*Department of Chemistry, School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
The first in situ preparation of triphenylbismuthane (tropon-2-yl)imide has been accomplished by the reaction of triphenylbismuth dichloride with 2-aminotropone. The imide is not isolated due to its moisture sensitivity, while it undergoes aza-Wittig type reaction with heterocumulenes leading to cyclohepta-annulated heterocycles in situ, and reacts also as an oxidizing agent of activated alcohols to give the corresponding carbonyl compounds under mild conditions.
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■ Synthesis of 4-Aryltetrahydroiso-quinolines: Application to the Synthesis of Cherylline
Somsak Ruchirawat,* Sopchok Tontoolarug, and Poolsak Sahakitpichan
*Labotratory of Medicinal Chemistry, Chulabhorn Reseach Institute, VipavadeeÅ@Rangsit Highway, Bangkok 10210, Thailand
Abstract
A concise route for the synthesis of 4-aryltetrahydroisoquinolines was developed using the addition of Grignard reagents to nitrostyrene derivatives as the key step. The application to the synthesis of cherylline was described.
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■ Four New Amaryllidaceae Alkaloids from Galanthus gracilis and Galanthus plicatus Subsp. byzantinus
Nehir Ünver, Seda Noyan, Belkis Gözler, Takant Gözler, Christa Werner, and Manfred Hesse*
*Organisch-chemisches Institut, Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland
Abstract
(+)-3-Epi-3,4-dihydro-3-hydroxygraciline (5), isolated from Galanthus gracilis of Turkish origin, is a new member of the gracilines, a recently established subgroup of the Amaryllidaceae alkaloids. G. plicatus subsp. byzantinus has furnished three new alkaloids, namely (+)-plicane (12), which is a new plicamine-type alkaloid, along with (+)-3-O-(3-hydroxybutyryl)tazettinol (13), and N-formylismine (15).
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■ An Efficient Method of Synthesizing Optically Pure N-Boc-4-bromo-N-methyl-1-tosyl-D-tryptophan Methyl Ester, a Key Intermediate in the Synthesis of Optically Active Ergot Alkaloids
Yuusaku Yokoyama,* Kumi Osanai, Masaharu Mitsuhashi, Kazuhiro Kondo, and Yasuoki Murakami*
*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
Optically pure N-Boc-4-bromo-N-methyl-1-tosyl-D-tryptophan methyl ester (D-4), a key intermediate in the synthesis of optically active ergot alkaloids such as chanoclavine-I (7) and costaclavine (8), was prepared from N-acetyl-4-bromo-D-tryptophan (D-11) obtained from 4-bromoindole (9) and DL-serine (10) in two steps.
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■ Regioselective Formation of Novel Functionalized 1-Aza-9-oxafluorenes
Andreas Hilgeroth,* Kristin Brachwitz, and Ute Baumeister
*Department of Pharmacy, Institute of Pharmaceutical Chemistry, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Germany
Abstract
A small series of novel 1-aza-9-oxafluorenes have been prepared by regioselective cycloaddition reaction of p-benzoquinone to the sterically unhindered side of unsymmetrically substituted N-acyl-1,4-dihydropyridines (1). The stereochemistry of the products is discussed on the basis of X-Ray crystal structure analysis of one starting structure (1a). The formation of pyridine derivatives by possible redox reaction of the adducts was not observed. Rotameric properties of the N-acyl-1,4-dihydropyridines are demonstrated by 1H and 13C NMR spectroscopy, thus stabilizing the 1,4-dihydropyridine system towards competing oxidation by the quinone.
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■ Novel Approaches to Optically Active Substituted 4,5-Dihydro-1,2,4-triazin-6(1H)-ones as Conformationally Constrained Peptidomimetics
Laurènt Saniere, Martine Schmitt, Nadia Pellegrini, and Jean-Jacques Bourguignon*
*Laboratoire de Pharmacochimie de la Communication Cellulaire, UMR 7081 du CNRS, Faculté de Pharmacie,74 route du Rhin, 67400 Illkirch, France
Abstract
Synthesis of 4,5-dihydro-1,2,4-triazin-6-ones bearing different chiral a-amino acid residues at the C3 and N1 positions are reported. Cyclocondensation of N-hioacylphthalimides with α-amino hydrazides afforded C3 functionalised dihydrotriazinones in good yields without detectable epimerisation. Moreover, N1-alkylation of the dihydrotriazinone ring with several α-bromo esters was performed with satisfactory yields. Interestingly, this alkylation reaction was found to be regioselective with respect to N4 and NHBoc. This class of compounds represents a new series of small conformationally constrained peptide derivatives.
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■ Synthesis of 2-Phenyloxazole Derivatives Containing Amino Acids as Insulin Sensitivity Enhancers for Treatment of Type II Diabetes
Margaret M. Faul,* Leonard L. Winneroski, Jeremy S. York, Matt R. Reinhard, Richard C. Hoying, William H. Gritton, and Samuel J. Dominianni
*Lilly Reserach Laboratories, A Division of Eli Lilly and Company, Chemical Process Research and Development Division, Indianapolis, IN 46285-4813, U.S.A.
Abstract
The search for Insulin Sensitivity Enhancers (ISE) for use in the treatment of Non-Insulin Dependent Diabetes Mellitus (NIDDM) has led to the preparation of N-[(phenylmethoxy)carbonyl]-O-[[4-[2-(2-phenyl-4-oxazolyl)-ethoxy]phenyl]methyl]-L-serine (1) and 7-[2-(2-phenyl-4-oxazolyl)ethoxyl]-L-1,2,3,4-tetrahydro-N-Cbz-isoquinoline-3-carboxylic acid (2), that contain a 2-phenyloxazole moiety linked to an amino acid in place of the 2,4-thiazolidinedione pharmacophore. The 2-phenyloxazole was incorporated into 1 and 2 in high yield by alkylation of 4-hydroxybenzaldehyde or methyl 7-1,2,3,4-tetrahydro-N-benzyloxycarbonyl-hydroxyisoquinoline-3-carboxylate with 2-(2-phenyl-4-oxazolyl)ethyl p-toluenesulfonate (16). Successful incorporation of serine into 1 required use of an N-trityl protecting group to minimize β-elimination and epimerization at the α-center.
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■ Reactions of Alkyl (Z)-2-[(E)-2-Cyano-2-(2-pyridinyl)ethenyl]amino-3-dimethylaminopropenoates with C- and N-Nucleophiles. The Synthesis of Fused 2H,5H-Pyran-2,5-diones, 4H-Pyrimidin-4-ones, and 1-Heteroaryl-1H-imidazole-4-carboxylates
Lucija Jukic, Jurij Svete,* and Branko Stanovnik*
*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, P.O. Box 537, SLO-1000 Ljubljana, Slovenia
Abstract
Alkyl (Z)-2-[(E)-2-cyano-2-(2-pyridinyl)ethenyl]amino-3-dimethylaminopropenoates (2) and (3) were transformed with C- and N-nucleophiles into alkyl 2-[2-cyano-2-(2-pyridinyl)ethenyl]amino-3-heteroarylpropenoates (10-13), 2H,5H-benzo[b]pyran-2,5-diones (14) and (15), 2H,5H-pyrano[4,3-b]pyran-2,5-dione (16), 2H,5H-pyrano[3,2-c]benzo[b]pyran-2,5-dione (17), alkyl 2-[2-cyano-2-(2-pyridinyl)ethenyl]amino-3-arylamino- (28-40), and 3-heteroarylaminopropenoates (41-43), pyrido[1,2-a]pyrimidin-4-ones (50-53), thiazolo[3,2-a]pyrimidin-4-one (54), benzothiazolo[3,2-a]pyrimidin-4-one (55), and 1-heteroaryl-1H-imidazole-4-carboxylate (56). Compounds (28-43) exist in (2E, 2’E) form or as a mixture of (2E, 2’E) as a major and (2Z,2’E) form as a minor isomer.
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■ Six New Heterocyclic Stilbene Oligomers from Stem Bark of Shorea hemsleyana
Toshiyuki Tanaka,* Tetsuro Ito, Ken-ichi Nakaya, Munekazu Iinuma, Yoshikazu Takahashi, Hiroshi Naganawa, and Soedarsono Riswan
*Gifu Prefectrual Institute of Health and Environmental Sciences, 1-1 Nakafudogaoka, Kakamigahara, Gifu 504-0838, Japan
Abstract
From the stem bark of Shorea hemsleyana (Dipterocarpaceae), four new stilbenoids with one or two dihydrofuran ring(s) [hemsleyanols C, D, hemsleyanosides E, F, and (-)-ampelopsin H] and a new stilbenoid with a carbonyl group (hemsleyanol E) were isolated. The structures including the relative configuration were elucidated on the basis of spectroscopic and chemical evidence.
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■ Polycyclic N-Heterocyclic Compounds. 57 Syntheses of Fused Furo(or Thieno)[2,3-b]pyridine Derivatives via Smiles Rearrangement and Cyclization
Takashi Hirota,* Kei-ichiroh Tomita, Kenji Sasaki, Kensuke Okuda, Masahiko Yoshida, and Setsuo Kashino
*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
An efficient methodology for the synthesis of thieno[2,3-c][2,7]naphthyridine (6), thieno[2,3-c]isoquinoline (11), furo[2,3-c]isoquinoline (14), [1]benzothieno[3,2-d]thieno[2,3-b]pyridine (21), and [1]benzothieno[3,2-d]furo[2,3-b]pyridine (26) skeletons from 4-[o-cyanoarylthio(or oxy)]butyronitriles with base via Smiles type rearrangement reaction followed by the cyclization is described.
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■ A Facile Synthesis and Chemical Properties of 3,4-Dihydro-2H-1,5,2-benzo[f]dithiazepin-3-ones with Potential Anticancer Activity
Elzbieta Pomarnacka,* Anita Kornicka, and Franciszek Saczewski
*Department of Chemical Technology of Drug, Medical University of Gdansk, 107 Gen. J. Hallera Str., 80-416 Gdansk, Poland
Abstract
The syntheses of 3,4-dihydro-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxides (8-11, 14, 17-20) and corresponding 1,1,5,5-tetraoxides (12, 13) are described. Reactivity of these compounds in their alcoholysis, alkaline hydrolysis and alkylation is also reported. Evaluation performed at the US National Cancer Institute (Bethesda) revealed the in vitro antitumor activity of 7-chloro-3,4-dihydro-8-methyl-4-phenyl-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (11).
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■ Unprecedented Rearrangement Reaction of Nitrile Oxides and a Sterically Congested 4-Ylidene-5-isoxazolone
Francesco Foti,* Giovanni Grassi, Francesco Risitano, Giuseppe Bruno, and Francesco Nicolo
*Dipartimento di Chimica Organica e Biologica, Università di Messina, Vill. S. Agata, I-98166 Messina, Italy
Abstract
The reaction between nitrile oxides and 4-diphenylmethylene-3-phenylisoxazol-5-one (5) proceeds in an unprecedented fashion to yield 4-diphenylmethylene-2,3,3-trisubstituted derivatives (10). Their structure was determined by an X-Ray diffraction study.
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■ Daphsaifnin, a Dimeric Coumairn Glucoside From Daphne oleoides
Muhammad Riaz and Abdul Malik*
*International Centre for Chemical Sciences, H. E. J. Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan
Abstract
Daphsafnin, A new dimeric coumarin glucoside, (1) was isolated from the roots of Daphne oleoides along with five known coumarins (2-6). The structure of 1 was established by the extensive spectroscopic studies including 2D-NMR and chemical analysis.
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■ Two Tricyclic Adducts from Consecutive Additions of Dimethyl Acetylene-dicarboxylate to 2,4-Di-t-butyl-3a,5a-dihydro-3H-cyclobuta[b]pyrrole: A Novel Formation of Cyclobuta[1’,2’-f]pyrrolo[1,2-b]oxazine Derivative
Shizuka Takami, Kyosuke Satake, and Masaru Kimura*
*Department of Chemistry, Faculty of Science, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan
Abstract
The tricyclic heterocycles (2) and (3) were newly synthesized by the addition reaction between 2,4-di-t-butyl-3a,5a-dihydro-3H-cyclobuta[b]pyrrole (1) and dimethyl acetylenedicarboxylate (DMAD). The structures were confirmed by the X-Ray structural analyses, and the pathway affording them was also proposed.
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■ A Concise Synthesis of (-)-endo-Brevicomin
John K. Gallos,* Loukia C. Kyradjoglou, and Theocharis V. Koftis
*Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 540 06, Greece
Abstract
A new method for the synthesis of (-)-endo-brevicomin from D-ribose in four steps is reported.