HETEROCYCLES

■ Hydrogenolytic Cleavage of C=O Bond in γ-Piperidone Derivatives

Waleria Wysocka

*Department of Chemistry, Adam Mickiewicz University, ul. Grunwaldzka 6, 60-780 Poznán, Poland

Abstract

The proton transfer via the hydrogen bond system of γ-aminoketones, dissolved in aqueous solution of strong acids, is postulated as the driving force for the hydrogenolytic cleavage of the C=O bond of γ-piperidone derivatives.

■ A One-Pot and Selective Preparation of 2-(N-Alkyl-4-chlorobutylamino)-4-chloroquinazolines

Hideki Miki

*Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe 658-8558, Japan

Abstract

A new and facile synthesis of 2-(N-alkyl-4-chlorobutylamino)-4-chloroquinazolines by the reaction of 2,4(1H,3H)quinazolinedione with N-alkylpyrrolidines in phosphoryl chloride is described.

■ The Reaction of 2-Chloro-4-methylthioquinazolines with Alkylamines in Dimethylformamide

Hideki Miki and Junji Yamada

*Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe 658-8558, Japan

Abstract

The reaction of 2-chloro-4-methylthioquinazoline with alkylamines in dimethylformamide afforded 2,4-bis(methylthio)-, 2-alkylamino-4-methylthio-, 4-alkylamino-2-chloro-, 4-alkylamino-2-methylthio-, and 2,4-bis(alkylamino)quinazoline. The relative easiness of displacement of the chlorine and/or the methylthio group in 2-chloro-4-methylthioquinazoline depended on the bulkiness of alkylamines.

■ Formation Mechanism of 2-(N-Alkyl-4-chlorobutylamino)-4-chloroquinazoline

Hideki Miki

*Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe 658-8558, Japan

Abstract

The reaction of 2,4(1H,3H)-quinazolinedione (1) with N-alkylpyrrolidine in phosphoryl chloride undergoes readily the reaction of a von Braun type through the formation of dichlorophosphate and a quaternary ammonium salt in sequence, which decomposes to give 2-(N-alkyl-4-chlorobutylamino)-4-chloroquinazoline (3). A conceivable reaction mechanism is discussed.

■ Structure of Cleomiscosin B, a Coumarino-Lignoid of Cleome viscosa Seeds

Anil B. Ray, Sunil K. Chattopadhyay, Chohachi Konno, and Hiroshi Hikino

*Department of Medical Chemistry, Institute of Medical Chemistry, Banaras Hindu University, Varanasi-221 005, India

Abstract

A new coumarino-lignoid cleomiscosin B has been isolated from the seeds of Cleome viscosa and its structure has been elucidated as I based on chemical and spectroscopic evidence which, in turn, has brought on the revision of the structure of eleomiscosin A as IV.

■ A Synthesis of (+)-2-Oxa-6-azabicyclo[3.3.0]octan-3-one (The Geissman-Waiss Lactone): A Synthon for Some Necines

Heinrich Rüeger and Michael Benn

*Department of Chemistry, The University of Alberta, Calgary, Alberta, T2N, 1N4, Canada

Abstract

The lactone (1), an intermediate in the Geissman-Waiss synthesis of retronecine and a potential synthon for other necines, was synthesised from 4-hydroxy-L-proline.

■ A Short Synthesis of 1-Phenyl-3-oxo-octahydroisoquinolines

Kai S. Ng, Peter S. Rutledge, and Paul D. Woodgate

*Department of Chemistry, University of Auckland, Private Bag 92019, Auckland, New Zealand

Abstract

Equimolar amounts of benzaldehyde and 1-cyclohexenylacetonitrile react with P₂O₅ — methanesulfonic acid to give a mixture isomeric 1-phenyl-3-oxo-octahydroisoquinolines in good yield.

■ Ring D Inversion of Protoberberine Alkaloids. Conversion of Berberine into Non-naturally Occurring 11,12-Oxygenated Protoberberines

Miyoji Hanaoka, Mitsuru Inoue, Misao Takahashi, and Shingo Yasuda

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

Abstract

Three methods were developed for the transformation of a naturally occurring 9,l0-oxygenated protoberberine, berberine into a non-naturally occurring 11,12-oxygenated protoberberine through ring D inversion via a corresponding spirobenzylisoquinoline.

■ Structures of Withaperuvin B and C, Withanolides of Physalis peruviana Roots

Mahendra Sahai, Partha Neogi, Anil B. Ray, Yoshiteru Oshima, and Hiroshi Hikino

*Department of Medical Chemistry, Institute of Medical Chemistry, Banaras Hindu University, Varanasi-221 005, India

Abstract

Two minor withanolides, withaperuvin B and C, have been isolated from the roots of Physalis peruviana. Their structures have been elucidated as those represented by formulae 1 and 2, respectively, based on chemical and spectral evidence.

■ A Simple Method for Introduction of Acyl Groups into Pyridine Nuclei via Trimethylstannyl-pyridines and -quinolines

Yutaka Yamamoto and Akihiko Yanagi

*Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

The 2-trimethylstannyl (TMSn) derivatives of pyridine and quinoline were directly treated with acyl chlorides to afford the corresponding 2-acyl-pyridines and -quinolines in good yields. On the other hand, replacement of the 3- and 4-TMSn groups by acyl groups was satisfactorily achieved by catalysis of palladium compound such as PdCl₂ or PdCI₂(PPh₃)₂.

■ The Synthesis of dl-Steporphine, 4-Hydroxyaporphine Type Alkaloids

Jun-ichi Kunitomo, Megumi Oshikata, Kiyoko Suwa, Kayoko Makayama, and Yoshiko Murakami

*Faculty of Pharmaceutical Science, Mukogawa-Women’s University, 11-68 Koushien Kyuban-Cho, Nishinomiya, Hyogo 663-8179, Japan

Abstract

A 4-hydroxyaporphine type alkaloid, steporphine (1), has been stereospecifically synthesized for the first time.

■ Synthesis of Pyrido[2,1-a]isoindol-6(2H)-one and Its Analogs

Yohshihito Abe, Akio Ohsawa, and Hiroshi Igeta

*School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Abstract

Treatment of o-(2-pyridyl)benzaldiacetate (1a) with HCI afforded pyrido[2,1-a]isoindol-6(2H)-one (3a). 6-Hydroxypyrido[2,1-a]isoindolium hydrochloride (5) was suggested to be an intermediate. Isoindolo[2,1-a]quinolin-11(5H)-one (3b) and isoindolo[l,2-a]isoquinolin-8(12bH)-one (3c) were obtained in a similar way. Enol isomers (e.g. 7) of 3a-c were not detected by ¹HNMR and ¹³CNMR spectrum.

■ Synthesis of Nucleic Acid Base Functionalized Cyclodextrins: The Nucleoside Analogue

Katsuyuki Nagai, Hirosato Kondo, Nobutomo Tsuruzoe, Kenji Hayakawa, and Ken Kanematsu

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

Abstract

The β-cyclodextrins functionalized with the nitrogen-bases of nucleic acid such as thymine, uracil, cytosine, and adenine by a flexible polymethylene bridge have been synthesized and their structures were determined on the basis of the spectroscopic data.

■ Regioselectivity of Reactions of 2-Furoyl-N-aryl Nitrile Imine with Some Dipolarophiles

Ahmad Sami Shawali, Hamdi Mahmoud Hassaneen, Abdel-Fattah Shetta, Abdou Osman, and Fathi Abdel-Galil

*Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt

Abstract

The regioselectivity of the cycloadditions of nitrile imines (1a-d), derived from 2-furoylhydrazidoyl chlorides (3a-d), to the C=C and C=S double bonds of the enol tautomer of acetylacetone and the resonance stabilized thiocyanate anion respectively was investigated. The results indicate that the reactions studied are dipole-LUMO controlled and that the larger orbital coefficient in the LUMO of 7 is on the carbon atom.

■ Novel Heterocycles from 3-Bromo-4-bromomethylcoumarins

Vernon G. S. Box and Crement G. Humes

*Department of Chemistry, Mona Campus, , University of the West Indies, Mona, Kingston 7, Jamaica

Abstract

Whereas 3-bromo-4-bromomethyl-7-methoxycoumarin reacted very reluctantly with phenoxides, it was rapidly converted into pyridinium salts by simply substituted pyridines. The novel tetracyclic salt (11) was formed from tne reaction with 2-aminopyridine. Some or the pyridinium salts show interesting pharmacological activities.

■ A Modified Bischler Synthesis of Some Tetracyclic Indole Derivatives

Anders Hallberg, Donald Deardorff, and Arnold Martin

*Department of Pharmaceutical Sciences, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, U.S.A.

Abstract

The synthesis of 6,7-dihydro-5H-indolo[1,7-ab][1]benzazepine, 5H-indolo[1,7-ab][1] benzazepine, pyrrolo[3,2,1-kl]phenothiazine and 1-phenylindole was accomplished by cyclization of the corresponding diarylaminoacetaldehydes. Carbazole-9-acetaldehyde gave 2,4-dicarbazol-9-yl-2-butenal. The aldehydes were obtained by acid catalyzed hydrolysis of the corresponding diethyl acetals, which differed considerably in their relative hydrolysis rates.

■ Novel Reactions via β-Carboline Intermediates

Seiichi Takano, Kozo Shishido, Yoko Imamura, and Kunio Ogasawara

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

Abstract

Novel reactions via some β-carboline intermediates have been described. Namely, the carboline(1a) gave the tetracyclic lactam(4a) when it was thermally condensed with the formyl ester(2), while its 9-methyl homologue(1b), on the same treatment, gave the 2-formylindole derivative(12). On the other hand, the carboline(13) yielded the tetracyclic lactam(16) when it was treated with butyryl chloride in the presence of triethylamine, whereas the carboline-acid chloride (18). prepared in situ from the amide-acid(17), took different course giving the 2-formylindole(23) on the same treatment.

■ Synthetic Studies on β-Lactam Antibiotics: Conversion of 2-Pyridone into Azetidin-2-one

Tetsuji Kametani, Tomoko Mochizuki, and Toshio Honda

*Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Azetidin-2-one (4), bearing a functionalized carbon atom at the C₄-position, was efficiently synthesized from 2-pyridone (1) by photolysis, followed by ozonolysis.

■ A Direct N-Acylation of Indole with Carboxylic Acids

Masanao Terashima and Masako Fujioka

*Faculty of Pharmaceutical Scicences, Higashinihonngakuen University, 1757 Kanazawa, Toubetu-cho, Ishikari-gun, Hokkaodo 061-0212, Japan

Abstract

A simple method for the N-acylation of indole is described. Indole (1) was directly acylated at nitrogen with various carboxylic acids (2) catalyzed by boric acid in moderate yield.

■ Backdonation and Interrelationships between ¹⁵N, ¹³C Chemical Shifts and Infrared Absorption Frequencies in Heterocyclic N-Oxides

William W. Paudler and Misa V. Jovanovic

*Department of Chemistry, Portland State University, Portland, Oregon 97207, U.S.A.

Abstract

1) A relationship has been shown to exist between the ¹⁵N chemical shifts of a number of N-oxides and their υ_NO absorption frequencies.
2) A similar relationship exists between the σ_NO ionization potentials of N-oxides and their υ_NO absorption frequencies.
3) The changes in ¹⁵N chemical shifts of these N-oxides are reflected in changes of the ¹³C chemical shifts of the carbons α to the N-oxide function.
4) By comparing the ¹⁵N chemical shift changes of the N-oxides and their oxygen protonated analogs, a measure of the extent of backdonation, relatable to the π-deficiency of the N-oxides, has been established.
5) The steric inhibition to backdonation in some appropriately di-substituted N-oxides has been estimated by means of their υ_NO frequencies and changes in the ¹³C chemical shifts of the α-carbons.

■ Synthetic Approaches to Dihydrothiophenes

Walter G. Blenderman and Madeleine M. Joullié

*Department of Chemistry, University of Pennsylvania, 231 South 34th Street Philadelphia, PA 19104-6323, U.S.A.

Abstract

This review surveys available synthetic procedures for the preparation of dihydrothiophenes.

■ Synthesis of Five-membered Heterocycles Involving N Atom from Aliphatic Nitro Compounds

Kazuho Harada, Eisuke Kaji, and Shonosuke Zen

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

■ 1,3-Dipolar Cycloaddition Reactions of Benzylidenecyanoamines

Otohiko Tsuge and Kazunori Ueno

*Research Institute of Industrial Science, Faculty of Engineering, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan

■ Reactions of Tetrakis(trifluoromethyl)-Dewar Pyrroles

Yoshiro Kobayashi, Akira Ando, Youichi Sugisawa, and Itsumaro Kumadaki

*Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

■ Direct Phenylation of Isoxazole Ring Using Palladium Catalysts: Synthesis of 4-Phenylmuscimol

Norio Nakamura, Yawara Tajima, and Kiyoshi Sakai

*Sankyo Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan

■ Synthetic Utility of 2-Oxazolones

Takehisa Kunieda, Tsunehiko Higuchi, Yoshihiro Abe, and Masaaki Hirobe

* Faculty of Pharmaceutical SciencesUniversity of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan

■ Synthesis and Reactions of Pyrrolidine Derivatives from Succinimide

Tatsuo Nagasaka, Fumiko Hamaguchi, Naganori Ozawa, Yoshiyuki Kosugi, Sayuri Esumi, and Sadao Ohki

*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

■ Thermal Reactions of 2-Azabicyclo[3.2.0]heptane-3,4-diones

Takehiro Sano, Yoshie Horiguchi, and Yoshisuke Tsuda

*Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan

■ Prenylation of Tryptophan Derivatives. Synthetic Approach to Fumitremorgin B and Brevianamide E

Masako Nakagawa, Kenji Matsuki, Kohichi Hasumi, Mikio Taniguchi, and Tohru Hino

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

■ Synthesis of Morphan Derivatives from Norbornadiene by Skeletal Transformation

Hiroo Inoue, Katsumi Umano, and Toshiki Origuchi

*Department of Applied Chemistry, College of Engineering, University of Osaka Prefecture, Sakai, Osaka 593-8531, Japan