HETEROCYCLES

■ Preface

Tetsuji Kametani

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

■ Preface

Oskar Jeger

*,

■ Profile and Scientific Contributions of Professor Kyosuke Tsuda

Shigenobu Okuda and Nobuo Ikekawa

*Institute of Applied Microbiology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8567, Japan

■ Bibliography

Kyosuke Tsuda*

*,

■ A New Efficient Coupling Reagent for Cyclic N -Methylanilide Formation

Masayuki Shimagaki, Hiroko Koshiji, and Takeshi Oishi*

*The Institute of Physical and Chemical Research, Wako-shi, Saitama 351-0198, Japan

Abstract

Treatment of the reagent (5) with the amino acid (11) in DMF afforded the active ester (12), which was added slowly to toluene at 95-100°C to produce the 15-membered cyclic N-methylanilide (13). The reaction proceeds under essentially neutral conditions.

■ Modification of α-Santonin VII. Synthesis of Z-4-Germacranolide

Takeshi Shimizu, Masahiro Saito, Yukinori Ohgoshi, Yasuo Fujimoto* and Takashi Tatsuno

*The Institute of Physical and Chemical Research, Wako-shi, Saitama 351-0198, Japan

Abstract

Z-4-germacranolides (heliangolides) were synthesized from α-santonin. The regio- and stereoselective introduction of Z-4-double bond info the cyclodecane ring required for the synthesis of naturally occurring heliangolide is performed in excellent yield via 5S-iodo derivatives of Z-9-germacranolides.

■ A New Approach to Ellipticine Analogues; Synthesis of 11-Hydroxy-5,6-dimethylpyrido[4,3-b]carbazole

Martin J. Wanner, Gerrit-Jan Koomen, and Upendra K. Pandit*

*Organic Chemistry Laboratory, University of Amsterdam, Nieuwe Achtergracht 129, 1018 WS Amsterdam, The Netherlands

Abstract

2-(2’-Indolyl)propionic ester reacts with nicotinoyl chloride to give a pyridyl ketone which, following quaternization and treatment with base, cyclizes to the pyrido[4,3-b]carbazole skeleton.

■ A Convenient Synthesis of Oxahomopentaprismane

Ken-ichi Hirao,* Yoshimi Kajikawa, and O. Yonemitsu, and Eiji Osawa

*Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan

Abstract

Attempts were made to explain the unique inertness of oxahomohypostrophene (2) to photocyclization with the aid of molecular mechanics calculations. By using Favorskii rearrangement of bromoketone (14) as a key step, a convenient synthesis of oxahomopentaprismane (1) from cyclopentadiene or hexachlorocyclopentadiene was achieved.

■ A Southern Army-Worm Antifeedant, 12β-Acetoxyharrisonin from an African Shrub Harrisonia Abyssinica

Hung-wen Liu, Isao Kubo, and Koji Nakanishi*

*Department of Chemistry, Columbia University, 3000 Broadway, Mail Code 3114, New York, New York 10027, U.S.A.

Abstract

The ether extract of Harrisonia abyssinica has yielded the limonoid 12β-acetoxyharrisonin 3 in addition to the known obacunone 1 and harrisonin 2. The two insect antifeedants (against Spodoptera), harrisonin and its 12β-acetoxy derivative, both possess a 6-keto-7-hemiketal moiety, which is not an artefact, and adopt a boat conformation for ring A; this aspect contrasts with that of obacunone which is not an army-worm antifeedant.

■ Site-selective Effect of N -Oxide Function to Methyl Groups on Six-membered N -Heteroaromatics

Takao Sakamoto, Hiroshi Yoshizawa, Hiroshi Yamanaka,* Yoshinobu Goto, Tokihiro Niiya, and Noriko Honjo

*Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan

Abstract

Reaction of 2,4-dimethylpyridine 1-oxide with ethyl benzoate under basic conditions afforded 4-methyl-2-phenacylpyridine 1-oxide, while the same reaction of 2,4-dimethylpyridine itself is known to afford 2-methyl-4-phenacylpyridine. Concerning the above contrast, the effect of N-oxide function to the relative reactivity of the 2- and 4-methyl group was investigated on pyridine, quinoline, pyrimidine, and quinazoline homologues. The higher reactivity of α-methyl groups was concluded to be general in the N-oxides of these N-heteroaromatics.

■ A Simple Synthesis of Borinane

Herbert C. Brown* and Ganesh G. Pai

*Wetherill Laboratory, Purdue University, West Lafayette, Indiana 47907, U.S.A.

Abstract

Hydroboration of 1,4-pentadiene with two molar equivalents of 9-borabicyclo[3.3.1]nonane (9-BBN) in n-hexane and subsequent reaction of the trialkylborane so formed with one molar equivalent of the borane-tetrahydrofuran complex (BH₃·THF) or the borane-dimethyl sulfide complex (BMS) forms borinane with regeneration of the 9-BBN. Addition of 100% excess (with respect to borinane) of triethylamine (Et₃N) results in selective complexation of the amine with borinane. Cooling the reaction mixture to -78°C crystallizes out the uncomplexed 9-BBN (~98% recovery). Treatment of the mother liquor with boron trifluoride-etherate (BF₃·OEt₂) removes the amine and liberates free borinane. Alternatively, 1,4-pentadiene can be hydroborated with the borinane-NEt₃ complex and the Et₃N pumped off from the trialkylborane product. BMS now generates pure borinane. The second procedure produces three moles of borinane from two, avoiding the necessity of a separation of products.

■ Heterocycles. XII. Chiral Benzo[c ]phenanthridines

Yoshihiro Harigaya, Seiko Takamatsu, Hiroko Yamaguchi, and Masayuki Onda*

*School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan

Abstract

Reaction of the (-)-epoxyhydroxy lactone (3) with methylamine stereospecifically gives the (+)-trihydroxy lactam (4) which is converted into the (+)-10b-hydroxychelidonine (7) and (+)-11-epichelidonine analogs (9) via several steps. The absolute configurations of these compounds are decided on the basis of that of (-)-3 and the spectral data observed.

■ Studies on Nucleoside Analogs. XXIV. Mono- and Disaccharide Isothiocyanates

Haruo Ogura* and Hiroshi Takahashi

*School of Pharmaceutical Sciences, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan

Abstract

The reaction of mono- and disaccharide bromide with Pb(SCN)₂ or AgSCN in dry benzene or benzene-toluene gives the respective mono- and disaccharide isothiocyanates and the confirmation of their stereochemistry of mono- and disaccharide isothiocyanates is described.

■ The Structure and Partial Synthesis of Nagarine. A Novel Alkaloid from the Chinese Drug, Aconitum nagarum var. heterotrichum F. dielsianum W. T. Wang

Naresh V. Mody, S. William Pelletier,* and Chen Szu-Ying

*Department of Chemistry, Institute for Natural Products Research, The University of Georgia, Chemistry Building, Athens, Georgia 30602-2556, U.S.A.

Abstract

Chemical investigation of the roots of Aconitum nagarum var. heterotrichum f. dielsianum W. T. Wang resulted in the isolation of a novel alkaloid, nagarine, along with two known alkaloids, aconitine and 3-deoxyaconitine. The structure of nagarine (1) was based on the carbon-13 NMR analysis. Subsequently, this structure was confirmed by a partial synthesis from delphisine. The structure of nagarine is unusual because it is the only C₁₉-diterpenoid alkaloid in which the C(15) hydroxyl group exists in the β-configuration.

■ Synthesis of 6,5’-Cyclo-5’-deoxyuridine: A Pyrimidine Nucleoside Fixed in anti Conformation

Tohru Ueda* and Satoshi Shuto

*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan

Abstract

Treatment of 2’,3’-O-isopropylidene-5’-bromo-5’-deoxy-5-chlorouridine with tri-n-butylstannane gave the 6,5’-cyclo-5,6-dihydro derivative, which was de-hydrochlorinated and deacetonated to furnish 6,5’-cyclo-5’-deoxyuridine, a fixed anti conformer of uridine. Bromination of a 6,5’-cyclo-5,6-dihydrouridine gave the 5-bromo derivative of the title compound.

■ The Partial Syntheses of Reserpiline and Isoreserpiline

Shin-ichiro Sakai,* Naoki Saito, Naohiro Hirose, and Etsuji Yamanaka

*Faculty of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

Reserpiline 4 and isoreserpiline 3 were first synthesized through 5,6-dimethoxyindole derivative 11, 12 and amine synthon 8 which was already derived from natural oxindole alkaloids 9, 10 and/or by the total syntheses.

■ Synthesis of Adamantane Derivatives. 57. Facil Generation and Cycloaddition Reactivity of N -Phenylsulfonyl-1- and -2-Adamantylnitrilimines via Base-induced Dehydrochlorination of N -(Phenylsulfonyl)-1- and -2-adamantanecarbohydrazonoyl Chlorides

Tadashi Sasaki,* Shoji Eguchi, and Yumo Tanaka

*Institute of Applied Organic Chemistry, Faculty of Engineering, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan

Abstract

Dehydrochlorination of N-(phenylsulfonyl)-1- and -2- adamantanecarbohydrazonoyl chlorides (7a and 7b) with triethylamine in the presence of dipolarophiles afforded the corresponding 1,3-dipolar cycloadducts (10a, 10b, 11a, 11b, 12a, 13a, 13b, 14a, 14b, and 15a) in 22-76% yields accompanied by the formation of linear dimer 9a and 9b, respectively.

■ Stereoselective Synthesis of (±)-Deethylaspidospermidine

Mitsutaka Natsume* and Iwao Utsunomiya

*Research Foundation Itsuu Laboratory, 2-28-10 Tamagawa, Setagaya-ku, Tokyo 158, Japan

Abstract

Conjugate addition of various carbanions to the enones 2 afforded 2,3-trans substituted piperidinones 3. (±)-Deethylaspidospermidine (12a) was synthesized from 1b via 5b, 7, and 11a in the stereoselective manner.

■ Synthesis and Glycosidic Bond Cleavage of 7-Methyl- and 7-Ethyladenosines: An Alternative Synthesis of 7-Alkyladenines

Tozo Fujii* and Tohru Saito

*Faculty of Pharmaceutical Scicences, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan

Abstract

7-Methyladenosine perchlorate (VIIa: X = ClO₄) was prepared in pure and crystalline form from N⁶-methoxyadenosine (I) by methylation with MeI at the 7-position followed by catalytic hydrogenolysis of the N⁶-methoxy group. 7-Ethyladenosine perchlorate (VIIb: X = ClO₄) was also synthesized from N⁶-benzyloxyadenosine (II) in an analogous manner. On treatment with H₂O at 98-100°C for 40 min, VIIa (X = ClO₄) and VIIb (X = ClO₄) produced 7-methyladenine (VIIIa) and 7-ethyladenine (VIIIb) in 84% and 55% yields. In 0.1 N aqueous HCl at 25°C, VIIa (X = ClO₄) and VIIb (X = ClO₄) were hydrolyzed in similar manners at rates of 2.22 ¥ 10^-3 min^-1 and 1.69 ¥ 10^-3 min^-1, respectively. Comparison of these rate constants with those of other three N-methyladenosine isomers X, XI, and XII has revealed that the relative ease of the hydrolysis of the glycosidic bond is in the order of 3- (XI) > 7- (VIIa) >> N⁶- (X) > 1-methyladenosine (XII).

■ Photochemistry of Azoles, Part VII. Photosolvolysis of Alkylmercaptoazoles.An Application to Some Acyclic Monoterpene Derivatives

Shigeo Iwasaki*

*Institute of Applied Microbiology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8567, Japan

Abstract

Salts derived from 2-alkylmercapto-1-methylimidazoles 1b-e and 3-alkylmercapto-4-methyl-1,2,4-triazoles 2b-d have been found to undergo photochemical heterolytic fission of the S-alkyl bond in aqueous or methanolic solution to give solvolysis-type products.

■ Photolysis of Homoconjugated Allene Ketones

Walentina Kudrawcew, Bruno Frei, Hans Richard Wolf, and Oskar Jeger*

*Laboratorium für Organische, Eidgenössischen Technischen Hochschule, Universitatstrasse 16,8092 Zürich, Switzerland

Abstract

UV-Irradiation (λ>280 nm) of the homoconjugated allene ketones 4 and 5 gives, in addition to small amounts of the ketodienes 8 and 17 (1,3-acyl shift), the enol ethers 9, 10 and 18, 19 respectively (cyclization process followed by 1,5-H-shift). However, on T-sensitization in acetone, 4 forms the spirodioxetane 13 in high yield. Irradiation of 4 in 2-propanol or ethanol affords the acetals 11 and 12.

■ Hydroxylation of Alkyl Groups on the Pyrazine Ring

Akihiro Ohta* and Minoru Ohta

*Tokyo College of Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Abstract

Treatment of THF solutions of 2,5-dialkylpyrazine 1-oxides with oxygen in the presence of bases gave the corresponding 2-hydroxypyrazine 1-oxides and dimers. On the other hand, when 2-chloro-3,6-dialkylpyrazine 1-oxides and 3,6-dialkyl-2-hydroxypyrazine 1-oxides were treated under the same conditions, hydroxylation occurred successfully at the α-position of the side chain.

■ Structure of Ephedradine D, a Hypotensive Principle of Ephedra Roots

Hiroshi Hikino,* Minoru Ogata, and Chohachi Konno

*Pharmaceutical Institute, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan

Abstract

From the crude drug “mao-kon”, the roots of Ephedra plants, a new macrocyclic spermine alkaloid ephedradine D exhibiting the hypotensive activity has been obtained whose stereostructure has been elucidated as shown in formula I based on chemical and physical evidence.

■ Propellanes. LXIII. Dithia[3.3.n]propellanes and Their HgCl₂ Complexes

Ishai Sataty,* Moshe Kapon, Menahem Kaftory, and David Ginsburg

*Department of Chemistry, Israel Institute of Technology, Haifa 32000, Israel

Abstract

Complexes of dithia[3.3.1], dithia[3.3.2], dithia[3.3.3]propellane and of dithia[4.3.3]propellene with HgCl₂ have been prepared. X-ray structures have been determined of most of the complexes and of the uncomplexed substrates.

■ Ring Transformations of Heterocycles via Ylide Intermediates: Synthesis of Hexahydro-2,3-diazepino[5,4-b]indoles from Tetrahydro-γ-carbolines

Yasumitsu Tamura,* Iwao Morita, Hidetsugu Tsubouchi, Hiroyuki Ikeda, and Masazumi Ikeda

*Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Toyonaka, Osaka 560-0043, Japan

Abstract

N-Amination of 2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles with o-(p-toluenesulfonyl)-N-alkylhydroxylamines followed by base treatment gave the ring expanded products, 1,2,3,4,5,6-hexahydro-2,3-diazepino[5,4-b]indoles.

■ Furanoditerpenoids from the Dorid Nudibranch Casella atromarginata

E. Dilip de Silva and Paul J. Scheuer*

*Department of Chemistry, University of Hawaii at Manoa, 2545 Tha Mall, Honolulu, Hawaii 96822-2275, U.S.A.

Abstract

The structures of six furanoditerpenoids isolated from a nudibranch, Casella atromarginata, were determined by spectral analysis and chemical interrelation. Two of the compounds, 1 and 5, are known sponge metabolites of Australian Spongia spp.; two more, 2 and 6, represent minor structural variants; and two, 3 and 4, are characterized by a more highly oxidized A-ring, which bears a monoenolized α-diketone function.

■ Microbial Transformation of 2’-Propoxy Analogs of (-)- and (+)-Dehydrogriseofulvin and (+)-2’-Demethoxydehydrogriseofulvin by Streptomyces cinereocrocatus

Yoshihiro Sato* and Taiko Oda

*Faculty of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, 1-5-30, Shiba-koen, Minato-ku, Tokyo 105-8512, Japan

Abstract

By the fermentation of Streptomyces cinereocrocatus, 2’-propoxy analogs of (-)- and (+)-dehydrogriseofulvin were both converted into the corresponding analog of (+)-griseofulvin and the same treatment of (+)-2’-demethoxydehydrogriseofulvin afforded (+)-2’-demethoxygriseofulvin and (+)- and (-)-2’-demethoxy-2’,3’-dihydrodehydrogriseofulvin, indicating that the (+)-substrates were isomerized into the corresponding (-)-enantiomers and subsequently transformed to the reduction products.

■ Nucleophilic Substitution of 4-Chloroguinoline 1-Oxide and Related Compounds by Means of Hydride Elimination

Masatomo Hamana,* Genji Iwasaki, and Seitaro Saeki

*Faculty of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

Abstract

The reaction of 4-chloroquinoline 1-oxide (1) with pinacolone and t-BuOK in t-BuNH₂ at -10~-15°C gives 4-chloro-2-pinacolylquinoline 1-oxide in good yield by means of hydride-elimination. Similar reactions of 1 with acetone, 2-butanone, acetophenone, and ethyl and t-butyl acetates occur when treated with t-BuOK or n-BuLi in t-BuNH₂ at -10~-15°C, or t-BuOK, KNH₂ or NaNH₂ in liq NH₃ at -70°C. Reactions of this type proceed also with quinoline 1-oxide (2), 3-bromoquinoline 1-oxide (3), p-chloronitrobenzene (4) and nitrobenzene.

■ Photochemical Rearrangements of 18-Hydroxylated Lanosterol Derivatives

Gerhard G. Habermehl,* Jürgen H. Kirsch, and Karl J.Reibstein

*Veterinary University, Bischofsholer Damm 15, D-3000 Hannover, Germany

Abstract

Several lanosterol derivatives with 18-hydroxyl group were subjected to the hypoiodite reaction. A new C-secosteroid was obtained as well as the desired 5-membered 18,20-epoxy compound.

■ Acid-induced Cyclization of 3-Benzyl-3,4-dihydro-2-pyrazinones:synthesis of 1,2,3,4,-5,6-Hexahydro-1,5-imino-3-benzazocine Derivatives

Hideshi Kurihara and Hiroshi Mishima*

*Central Research Laboratories, Sankyo Co.,Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140 Japan

Abstract

3,4-Dihydro-4-ethoxycarbonyl-2-pyrazinones (3), which can be prepared by cyclization of dipeptide aldehyde acetals (2) in the presence of a catalytic amount of proton acid, were shown to be useful intermediates for the preparation of complex heterocycles by acid-induced C-C bond formation. The acid-induced intramolecular cyclization of the intermediates (3) afforded regioselectively 1,5-ethoxycarbonylimino-3-methyl-1,2,5,6-tetrahydro-3-benzazocin-4(3H)-one (4) in quantitative yield. The structural characterization of the cyclization product (4) and its derivatives (6 and 7) was carried out mainly by the analysis of the NMR spectra.