HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Ken'ichi Takeda's Special Issues, Vol. 5, No. 1, 1976
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■ 1H NMR Solvet Sifts Induced by Hexafluorobenzene in Lactones, Lactams, Acid Anhydrides and Imides
Isao Horibe, Hiroko Shigemoto, and Kazuo Tori*
*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan
Abstract
Aromatic solvent-induced shifts (ASIS) with hexafluorobenzene in 60-MHz 1H nmr spectra of lactones including sesquiterpenic ones, lactams, carboxylic acid anhydrides and imides were examined to demonstrate that the ASIS method becomes more useful in signal assignments and structure elucidation of lactones and lactams when hexafluorobenzene is employed as a solvent rather than benzene or pyridine.
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■ N-Monomethylation of Aromatic Primary Amines
Kusuo Horiki*
*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan
Abstract
N-Monomethyl aromatic amines were conveniently prepared by reduction of 3-(N-arylaminomethyl)-5,5-dimethylhydantoin (2) with sodium borohydride in dimethyl sulfoxide.
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■ Formation of a p-Quinone Methide in the Presence of Methanol
Osamu Hoshino, Hiroshi Hara, Masashi Ogawa, and Bunsuke Umezawa*
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
(±)-4β-Acetoxythaliporphine (IV) reacted readily with methanol to give (±)-4β-methoxythaliporphine (V). Consequently, a facile formation of p-quinone methide (XI) as a key intermediate was deduced.
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■ Acid-catalyzed Reaction of 1-Substituted 10-Acetoxy-8-chloro-6-methoxy-2-methyl-7-oxo-Δ5,6,8,9-hexahydroisoquinolines
Hiroshi Hara, Osamu Hoshino, and Bunsuke Umezawa*
*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
Treatment with trifluoroacetic acid of the p-quinol acetates (VIa, b) derived from 1-benzyl-8-chlorotetrahydroisoquinolines (Va, b) gave the corresponding 8-chloromorphinandienones (VIIa, b), 1-chloroisopavines (VIIIa, b), and 4-β-hydroxyaporphines (IXa, b), respectively. By similar reactlon of p-quinol acetates (XIIIa-c), 8-chlorohomomorphinandienones (XIVa-c), 1-chlorohomoisopavines (XVa-c), and 4β-hydroxyhomoaporphines (XVIa, b) were yielded, respectively.
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■ Formation and Stereochemistry of 2-Aryl-2-ethyl-1,2,3,5,6,11b-hexahydro-11H-indolo[3,2-g]indolizine Previously Taken for to Be 3,4-Dehydroquebrachamine
Seiichi Takano,* Masaaki Sato, Susumi Hatakeyama, Michiyasu Hirama, and Kunio Ogasawara
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Formation and stereochemistry of 2-allyl-2-ethyl-1,2,3,5,6,11b-hexahydro-11H-indolo[3,2-g]indolizine (3:R=Et) previously taken for to be 3,4-dehydroquebrachamine (2:R=Et) is reported.
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■ Diterpenic Lactones of Mallotus repandus
Takeshi Kawashima, Tetsuo Nakatsu, Yoshimasa Fukazawa, and Shô Itô*
*Department of Chemistry, Graduate School of Science, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
From the title plant obtained in Sarawak, two lactones were isolated and characterized in addition to lupeol and taraxerol. Mallotucin A, 1, m.p. 201 -202 °, was found to be identical with teucvin isolated from Teucrium viscidum var. Miquelianum: The present result reinforces the previous structure assignment. Mallotucin B, 2, m.p. 131.5-132.5 °, was found to be the first diterpenoid with geminal methoxycarbonyl groups.
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■ Rections and Synthetic Applications of β-Ketosulfoxides. VII. A Novel Synthesis of Pyranocarbazole Alkaloids, Girinimbine and Murrayacine
Yuji Oikawa* and Osamu Yonemitsu
*Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan
Abstract
On treatment with p-toluenesulfonic acid in acetonitrile, 1-(3-indolylmethyl)ethyl-4-methyl-1-methylsulfinyl-3-pentenyl ketone (6a) prepared from methyl indoleisobutyrate (8) with sodium methylsulfinylmethide followed by prenylation gave dihydrogirinimbine (7) through three consecutive acid-catalyzed reactions. Compound (7) was converted into N-phenylsulfonamide (11), which was dehydrogenated with N-bromosuccinimide in the presence of azobisisobutyronitrile to afford N-phenylsulfonylgirinimbine (12). Lithium aluminium hydride reduction of 12 gave girinimbine (4). Oxidation of 4 with DDQ furnished murrayacine (5). Under similar conditions, 7 gave cycloheptaphylline (13). The results in this communication may provide a shortcut and convenient method for the synthesis of pyranocarbazole alkaloids.
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■ Studies on Potential Antitumor Agents I. Thiosemicarbazones of p-Chlorophenyl- and m-Chlorophenylpyridine-2-carboxaldehydes
Chao-Tung Chen,* Shih-Fong Chen, and Shwu-JIuan Lee
*Institutue of Chemistry, Academia Sinica, 128, Yan-Chiu-Yuan Road, Sec II, Nankang, Taipei,11529, Taiwan, R.O.C.
Abstract
Thiosemicarbazones of eight p- and m-chlorophenylpyridine-2-carboxaldehydes have been synthesized. The biological activity of these compounds was evaluated by animal test. 4-(p-Chlorophenyl)pyridine-2-carboxaldehyde thiosemicarbazone was found to possess potential antitumor activity with low toxicity.
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■ Nucleosides and Nucleotides. Part 9. Syntehsis of Dinucleoside Monophosphates Containing 2’-Deoxycytidine and 1-(2’-Deoxy-β-D-ribofuranosyl)-2(1H)-pyridone
Nico Cerletti and Christoph Tamm*
*Institut für Organische Chemie, Universitat Basel, St. Johanns-Ring 19
CH-4056 Basel, Switzerland
Abstract
Condensation of 1-(5’-O-monomethoxytrityl-2’-deoxy-β-D-ribofuranosyl)-2(1H)-pyridone ((MeOTr)Πd, 4) and N4-anisoyl-3’-O-acetyl-2’-deoxycytidine-5’-phosphate (pCdan (Ac), 5) using an excess of dicyclohexylcarbodiimide (DCC) in absolute pyridine yielded the dinucleoside monophosphate (MeOTr)ΠdpCdan (6). Successive removal of the protecting groups of compound 6 led to the partially protected dinucleoside phosphates (MeOTr)ΠdpCd (7) and ΠdpCdan (8), and to the free dinucleoside monophosphate ΠdpCd (9). The enzymatic degradation of 9 by the phosphodiesterases I and II was complete and gave Πd and pCd, and Πdp and Cd respectively with the expected ratio of 1 : l.
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■ 1,3-Dipolar Cycloaddition of 4-Alkoxy-6-methylpyrimidine N-Oxides
Hiroshi Yamanaka,* Setsuko Niitsuma, Takao Sakamoto, and Michinao Mizugaki
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
While 1,3-dipolar cycloaddition of 4-ethoxy-6-methylpyrimidine N-oxide (Ia) with phenyl isocyanate gave the expected product, 2-anilino-4-ethoxy-6-methylpyrimidine (II), the reaction of Ia with phenyl isothiocyanate afforded 3-phenyl-7-methyl-2,3-dihydro-oxazolo[4,5-d]pyrimidine-2-thione (IV).
The reaction of 4-alkoxy-6-methylpyrimidine N-oxides (I) with dimethyl acetylenedicarboxylate afforded methyl 4-alkoxy-6-methyl-2-pyrimidineacetates (IX).
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■ Stereochemistry of Nonoxidative Photocyclization of Indole-2-carboxanilides to an Indolo[2,3-c]quinoline System
Yuichi Kanaoka,* Sadao Nakao, and Yasumaru Hatanaka
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
Nonoxidative photocyclization of indole-2-carboxanilides (1a and 1b) yielded mainly the 6a-11b cis isomers of indolo[2,3-c]quinolin-6-one 5. By contrast, from the N-methyl homologs (1c and 1d) only the trans isomers 4 were obtained. The mechanism was explained in terms of the dual pathways involving a sigmatropic 1,5-hydrogen shift and a competing “solvent-mediated” course.
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■ Introduction of Substituents to C3 of Yohimbinoid Skeleton
Norio Aimi,* Yoshihisa Asada, Shizuko Tsuge, Teruo Kohmoto, Kin’ichi Mogi, and Shin-ichiro Sakai
*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
Chlorination took place at the nucleophilic centres of tabersonine (1) and yohimbine (4) when their hydrochlorides were oxidized with m-chloro perbenzoic acid. Chloroindolenine N-oxide (5), thus obtained from yohimbine, was susceptible to nucleophilic attack at C3 position to give stable 3-substituted yohimbine Nb-oxides. No indication of the rearrangement to oxindole was observed.
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■ Iwamide: A New Phenolic Amide Derived from a Quaternary Banzo[c]phenanthridine Alkaloids
Tsutomu Ishikawa and Hisashi Ishii*
*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Abstract
The structure of iwamide (I) was established by the fact that decarine (II) was chemically transformed into iwamide (I) using Baeyer-Villiger like oxidation of an immonium group.
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■ Conversion of Caprolactam to Eight-membered Ene-lactam
Takeshi Oishi,* Mineo Fukui, Yoshio Ban, and Msanori Honda
*The Institute of Physical and Chemical Research, Wako-shi, Saitama 351-0198, Japan
Abstract
Dichlorocarbene adduct of N-acetyl ketene-O,N-acetal(II) derived from caprolactam afforded the homologous ene-lactam on LiAlH4 reduction followed by base treatment.
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■ Product Distribution in the Ribosylation Reactions of Adenine and 1-Deazapurine in the Presence of Stannic Chloride
Tokuo Itoh* and Yoshihisa Mizuno
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
Product distribution has been examined in the ribosylation of adenine and 1-deazapurine as well as their trimethylsilyl derivatives in the presence of stannic chloride. It was found that each of the reaction parameters (the presence or absence of trimethylsilyl protection, reaction time, and the amount of stannic chloride) exerts a profound influence on the product distribution. Reaction conditions favorable to the formation of otherwise quite inaccessible 7-ribosyladenines were developed.
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■ Synthesis of 3-Hydroxy Cephems
Hans Rudolf Pfaendler,* Phillip Andrew Rossy, Jacques Gosteli, and Robert Burns Woodward
*Woodward Research Institute, 4002 Basel, Switzerlamd
Abstract
The compounds 2, readily produced from natural penicillin V, are converted to 3-hydroxy cephems 1 through an efficient three-step reaction sequence.
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■ Synthesis and Circular Dichroism of Some trans-5,5a,6,7,8,9,9a,10-Octahydrobenzo[g]quinoxalines (Octahydrobenzo[g]quinoxalines)
Günther Snatzke* and György Hajós
*Lehrstuhl für Strukturchemie, Ruhr-Universität Bochum, Postfach 10 21 48, D-4630 Bochum 1, Germany
Abstract
Starting from trans-decalone-2 several optically active pyrazine derivatives with chiral second sphere have been prepared. The cd of the parent compound, 5,5a,6,7,8,9,9a,10-octahydrobenzo[g]quinoxaline (+)-VII reveals four Cotton effects (in isooctane:band I at 327 nm, band II at 270 nm, band III at 228 nm, band IV at 210 nm) which could be assigned to transitions to the following excited states: 1B3u, 1B2u, 1B2g, and 1B1u. The signs of these Cotton effects can be correlated with those of related octahydroanthracenes and ketones with chiral second sphere. The cd spectra of the mono and diprotonated compound support this assignements. The cd spectra of several 2-substitution products are given.
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■ Synthesis of 9-Azaprostaglandin Analogs
Gerard P. Rozing, Henk de Koning,* and Henderikus O. Huisman
*Laboratory of Organic Chemistry, University of Amsterdam, Nieuwe Achtergracht 129,1018 WS Amsterdam, The Netherlands
Abstract
9-Deoxy-9-azaprostaglandin analogs are obtained in eight steps, starting from ethyl N-ethoxycarbonylglycinate and diethyl 2-decenedioate.
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■ A Novel Oxidation of Qunaldine N-Oxide
Hirohisa Saito, Hideki Muro, Seitaro Saeki, and Masatomo Hamana*
*Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Abstract
Treatment of quinaldine N-oxide (5) with thallium triacetate or lead tetraacetate in acetic acid or/and acetic anhydride leads to the formation of 2-acetoxymethylquinoline N-oxide (2), diacetate of quinaldaldehyde (3), quinaldaldehyde (4) and quinaldaldehyde N-oxide (5). The selective preparation of 2, 3, 4 or 5 can be effected by adjusting the reaction conditions.
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■ Hydroxyalkylation of N-Alkoxyquinaldinium and -lepidinium Perchlorates
Hiroshi Noda, Hisao Ekimoto, and Masatomo Hamana*
*Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
Abstract
Irradiation of N-alkoxyquinaldinium or -lepidinium perchlorate in alcohol affords 4- or 2-hydroxyalkylated methylquinoline and a small amount of 8-alkoxy-methylquinoline. Hydroxymethylation of the N-ethoxy salts occurs also homolytically in high yields on treatment with methanol and ammonium peroxydisulfate.
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■ β-Lactones as Reagents in Protein Chemsitry. The Inactivation of Pepsin with β-Propiolactone
Richard N. Armstrong and Emil Thomas Kaiser*
*Departments of Biochemistry and Chemistry, University of Chocago, Chocago, Illinois 60637, U.S.A.
Abstract
Treatment of pepsin with β-propiolactone results in the alkylation of 1-2 methionine residues and the esterification of an aspartate residue. The modified enzyme is characterized by a marked (20-fold) decrease in catalytic efficiency toward benzyloxycarbonyl-histidyl-p-nitrophenyl-alanyl-phenylalanyl methyl ester. The results suggest that the aspartate alkylated is in the active site.
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■ Biosynthetic Studies with 13C: A Novel Favorsky Rearrangement Route to the Fungal Metabolite Aspyrone
Masato Tanabe,* Masakazu Uramoto, Takashi Hamasaki, and Lewis Cary
*Pharmaceytical Chemistry Department, Life Sciences Division, Stanford Research Institute, Menlo Park, California 94025, U.S.A.
Abstract
The 13C-nmr investigation of the biosynthesis of the pyrone metabolite 2-(1’,2’-epoxypropy1)-5,6-dihydro-5-hydroxy-6-methylpyran-2-one, aspyrone, isolated from A. melleus is described. Labeling distribution and incorporation level data from 1-13C-acetate, 2-13C-acetate and 1,2-13C-acetate supports a proposed Favorsky rearrangement route from a linear pentaketide unit for the biosynthesis of this fungal metabolite. 13C-nmr chemical shift assignments and carbon-carbon coupling data are presented. A Favorsky route is also proposed to account for bisfuran ring formation in aflatoxin and sterigmatocystin biosynthesis
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■ Sciadoline, A New Type of Bisbenzylisoquinoline Alkaloid
Keiichi Takahashi and Michael P. Cava*
*Department of Chemistry, University of Pennsylvania, 231 South 34th Street Philadelphia, PA 19104-6323, U.S.A.
Abstract
Sciadoline, a new alkaloid from Sciadotenia toxifera Krukoff and A. C. Smith (Menispermaceae), has been assigned structure II. It is the first example of a head-to-tail bisbenzylisoquinoline base which contains a completely aromatic isoquinoline unit.
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■ 2-Methoxydihydrohelenalin from the Rhizoma of Sendai Helenium autumnale L
Yoshikazu Kondo,* Fumio Hamada, and Fumihiko Yoshizaki
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Helenalin and 2-methoxydihydrohelenalin II, a first naturally occurring pseudoguaianolide, were isolated from the rhizoma of Sendai Helenium autumale (Compositae). The structure and stereochemistry of II were confirmed on the basis of chemical and physical means.
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■ Reactions of Halothiophenes with Acetone Enolate and Amide Ions
Joseph F. Bunnett* and Bernhard F. Gloor
*University of California, Santa Cruz, U.S.A.
Abstract
Acetone enolate ion undergoes photostimulated reaction with 2-chloro-, 2-bromo- and 3-bromothiophenes in liquid ammonia, affording mono- and dithienylacetones in fair to good yields. 3-Bromothiophene reacts with the same enolate ion under stimulation by solvated electrons to form mono- and di(3-thienyl)acetones in lower yield accompanied by the corresponding secondary alcohols, except that in the presence of excess KNH2 only debromination to thiophene occurs. Solvated electron-stimulated reactions of 2-chloro- and 2-bromothiophenes with acetone enolate ion give mainly thiophene and little thienylation. Under N2, 3-bromothiophene and KNH2 give 3-aminothiophene in high yield, but not much reaction occurs under an atmosphere of air. These reactions are believed to occur by the SRN1 mechanism. They suggest that substitutions by the SRN1 mechanism may be generally useful in the thiophene series, especially for the preparation of 3-substituted thiophenes.
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■ Novel Pyridazinium Ion Synthesis. Reaction of Diaminocyclopropenium Ion with Diazoalkanes
Zen-ichi Yoshida,* Hisatoshi Konishi, Keizo Hayashi, and Hisanobu Ogoshi
*Department of Synthetic Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan
Abstract
The reaction of bis(diisopropylamino)cyclopropenium perchlorate (1) with an excess of RCHN2 (R: H, CH3) afforded 3,4-bis(diisopropylamino)-6-R-pyridazinium perchlorate (2a, b). This reaction provides a novel synthetic method of pyridazinium compounds.
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■ The Reaction of Oxazoles with Singlet Oxygen. IV. Imino Anhydride Intermediates
Harry H. Wasserman* and George R. Lenz
*Department of Chemistry, Yale University, P.O. Box 6666, New Haven, Connecticut 06511, U.S.A.
Abstract
Reaction of 2-aryl-4,5-polymethylene oxazoles with singlet oxygen yields N-aroyl imino anhydrides. If the polymethylene bridge is large enough a further rearrangement to triamides may take place.
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■ Reactions of Stable Ylidic 1-Thianaphthalene with Electrrophiles. A New Ring Expansion Reaction
Mikio Hori,* Tadashi Kataoka, Hiroshi Shimizu, and Harumi Aoki
*Department of Pharmacognosy, Gifu College of Pharmacy, 6-1 Mitahora-higashi 5-chome, Gifu 502-8585, Japan
Abstract
Reactions of 2-cyano-1-methyl-4-phenyl-1-thianaphthalene (1) with electrophiles, such as tetracyanoethylene, maleic anhydride, and 4-phenyl-1-thianaphthylium perchlorate gave the dimeric compound (II) of 1, but not any cycloaddition products. However, the treatment of 1 and dimethyl acetylenedicarboxylate afforded a new ring expansion product (III) having sulphur-containing nine-membered ring.
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■ Synthesis of 3-Substituted Cephems from Penicillins via 4-Dithio-2-azetidinone Intermediates
Yoshio Hamashima,* Tadatoshi Kubota, Koji Ishikura, Kyoji Minami, Kazuya Tokura, and Wataru Nagata
*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan
Abstract
Cyclization of monocyclic dithioazetidinones 9 to the 3-substituted cephems is accomplished. When substituents at the β position of esters 9 are electron withdrawing such as chloro or sulfonyloxy, the benzothiazol-2-ylthio group migrates to position 3 of the cephem nucleus to give 3-thio derivatives 5 and 6. In contrast, when the substituents at the β position are weakly electron withdrawing, normal cyclization occurs giving 3-acyloxy derivatives 10. Reaction of γ-bromo-β-keto ester 16 with sodium borohydride and successive treatment with triphenylphosphine affords 3-hydroxycephem 11 albeit in poor yield. Base treatment of γ-bromo enamino ester 15 or γ-bromo-β-acetoxy ester 20 gives the corresponding 2,3-bis-substituted cephems 18 or 21.
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■ Interne Photocyclisierungen von Bi-1,2-dihydroisochinolinen und eines Methylen-bis-naphthalinones
Yushin Nakamura, Janos Zsindely, and Hans Schmid*
*Organisch-chemisches Institut, Universität, Rämistrasse 76, CH-8001 Zürich, Switzerland
Abstract
The bi-dihydro isoquinoline derivative rac-1 upon short triplet sensitized irradiation leads in high yield by an internal [2+2] cyclisation to product 3 (scheme 1). Reduction with di-isobutylaluminium hydride gives the bis-amine 4. Analogous irradiation of meso-1 gives the expected cyclisation product 5 only in moderate yield; the main product is again 3. Its formation must have been preceded by a photochemical meso-1 → rac-1 isomerization. The 3,3’-dimethyl derivates rac-2 and meso-2 undergo similar internal photocyclisations (scheme 1).
The structure of the above mentioned compounds was established by spectroscopic methods, especially 1H-NMR-spectra. A cyclobutane derivative, namely 13, is also formed upon direct irradiation of the bisnaphthalene derivative 10. 10 is a component of the equilibrium mixture that is formed by heating the bis-allylether 11 to 160 °. The main components of this equilibrium mixture, however, are 11 and 12.