HETEROCYCLES

■ Biographical Data

Shigeru Oae*

*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki 305-8571, Japan

■ Bibliography

Shigeru Oae

*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki 305-8571, Japan

■ A Tribute to the Contributions of Professor Shigeru Oae in Heterocyclic Chemistry

Waichiro Tagaki

*Department of Applied Chemistry, Faculty of Engineering, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan

■ Simple Procedure for the Synthesis of 2,5-Bis(silylated) Thiophene S-Oxides with m-Chloroperbenzoic Acid in the Presence of BF₃(Et₂O)

Naomichi Furukawa,* Shaozhong Zhang, Soichi Sato, and Masato Higaki

*Tsukuba Advanced Research Alliance Center, Department of Chemistry, University of Tsukuba, Tsukuba, Ibaraki 305, Japan

Abstract

Oxidation of 2,5-bis(silyl)thiophenes (1) with m-chloroperbenzoic acid (m-CPBA) in the presence of BF₃(Et₂O) gave the corresponding S-oxides (2) in moderate yields, while, without BF₃(Et₂O), the oxidation gave solely the corresponding thiophene S-dioxides (3) and no S-oxide was obtained at all. This procedure was successfully applied to the synthesis of other 2,5-bis-substituted thiophene monooxides.

■ Syntheses of Imidazoles and Pyrroles: BetMIC and TosMIC as Complementary Reagents

Alan R. Katritzky,* Dai Cheng, and Richard P. Musgrave

*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, U.S.A.

Abstract

p-Tolylsulfmylmethyl isocyanide (TosMIC) and benzotriazol-1-yl-methyl isocyanide (BetMIC) were compared as to their synthetic utilities for the synthesis of imidazoles and pyrroles and found to be complementary.

■ Synthesis of β- and Iso-β-cycloawaodorin

Mugio Nishizawa,* Hiroshi Imagawa, Ikumi Hyodo, Yukiko Kan, and Hidetoshi Yamada

*Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihamabouji, Yamashiro-machi, Tokushima, 770-8514, Japan

Abstract

Cyclic heptamers of L-rhamnose, β-cycloawaodorin and a stereoisomer, have been prepared by means of α-selective thermal glycosylation and DMTST induced cycloglycosylation. These novel oligosaccharides have characterized by nmr experiments as well as high resolution FAB mass spectra.

■ Synthesis of Highly Congested Bi- and Terthiophenes; 3,4,3',4'-Tetra-tert-butylbithiophene and 3',4'-Di-tert-butyl-2,2':5'2''-terthiophene

Juzo Nakayama,* Yo Ting, Yoshiaki Sugihara, and Akihiko Ishii

*Department of Chemistry, Faculty of Science, Saitama University, Saitama, Saitama 338-8570, Japan

Abstract

The Pd(PPh₃)₄-catalyzed coupling of 3,4-di-tert-butyl-2-thienylmagnesium bromide with 2-bromo-3,4-di-tert-butylthiophene gave 3,4,3’,4’-tetra-tert-butyl-2,2’-bithiophene (5) in moderate yield. X-Ray single crystal structure analysis of 5 revealed that its thiophene rings remain planer, but their plane is perpendicular to each other. The synthesis of 3’,4’-di-tert-butyl-2,2’:5’,2”-terthiophene in a similar way is also described.

■ 2-Methyl-4-nitroisoxazolin-5-one: Ring Transformation to 3-Nitropyrroles

Masahiro Ariga,* Nagatoshi Nishiwaki, Yuko Miwa, Keita Tani, and Yasuo Tohda

*Department of Chemistry, Osaka Kyoiku University, 4-698-1 Asahigaoka, Kashiwara, Osaka 582-8582, Japan

Abstract

Ring transformation of 2-methyl-4-nitroisoxazolin-5-one with some enolate anions afforded 3-nitropyrroles. A ring-opened intermediate of the ring transformation was isolated.

■ Synthesis and Chemiluminescence of 1,3-Disubstituted 4-Hydroxypyrazolo[4',3':5,6]pyrido[2,3-d]pyridazine-5,8(6H,7H)-diones

Yoshinori Tominaga,* Noriko Yoshioka, Hiroki Minematsu, and Seigo Kataoka

*Faculty of Pharmaceutical Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

Reanions of 1,3-disubstituled 5-aminopyrazole-4-carboxylate derivatives (1a-c) with dimethyl acetylenedicarboxylate gave the corresponding dimethyl 1,3-disubstituted 4-hydroxypyrazolo[3,4-b]pyridine-5,6-dicarboxyIate(2a-c) which reacted wilh hydrazine hydrate to give 1,3-disubstituted 4-hydroxy-1H-pyrazolo[4’,3’:5,6]pyrido[2,3-d]pyridazine-5,8(6H,7H)-diones (3a-d). These tricyclic pyridazine derivatives were alternatively synthesized from 4-hydroxypyrrolo[3,4-e]pyrazolo[3,4-b]pyridine-5,7-diones (7a-c) prepared by reactions of 5-aminopyrazoles (1e-g) with 1-methyl-3-methylthio-4-methoxycarbonylmaleimide (5) followed by Gould-Jacacobs reaction. These tricyclic pyridazine derivatives were evaluated for chemiluminescence. 4-Hydroxy-3-methylthio-1-phenyl-1H-pyrazolo[4’,3’:5,6]pyrido[2,3-d]pyridazine-5,8(6H,7H)-dione (3d) showed the greatest chemiluminescence intensity in the presence of H₂O₂ and peroxidase in a solution of phosphate buffer at pH 10.

■ Synthesis of a Fluorine Analog of Hematoporphyrin by Ring Closure

Masaaki Omote, Akira Ando, Toshiyuki Takagi, Mayumi Koyama, and Itsumaro Kumadaki*

*Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata-shi, Osaka 573-0101, Japan

Abstract

Benzyl 3,5-dimethyl-2-pyrrolecarboxylate (1) was converted to 4-(2,2,2-trifluoro-1-hydroxyethyl) derivative (2) on treatment with trifluoroacetaldehyde ethyl hemiacetal in the presence of zinc chloride. After protection of the hydroxy group, 2 was converted to benzyl 4-methyl-3-(2,2,2-trifluoro-1-methoxyethyl)2-pyrrolecarboxylate (9) and benzyl 5-acetoxymethyl-3-methyl-4-(2,2,2-trifluoro-1-methoxyethyl)-2-pyrrolecarboate (10). Both esters were condensed to a dipyrrolomethane compound (11), which was debenzylated, decarboxylated, and condensed with a bottom half of the porphyrin to give a hexafluorohematoporphyrin derivative (14), potentially useful for photodynamic therapy of cancer.

■ Studies with Plant Cell Cultures of the Chinese Herbal Plant, Tripterygium wilfordii. Synthesis and Biotransformation of Diterpene Analogues

James P. Kutney,* Kang Han, Francisco Kuri-Brena, Radka K. Milanova, and Malcolm Roberts

*Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, B.C. V6T 1Z1, Canada

Abstract

Synthetic routes to a series of diterpene analogues from dehydroabietic acid (1) are presented. These synthetic compounds are then utilized as substrates in biotransformation experiments with the cells of a stable cell line (coded as TRP4a) of the Chinese herbal plant, Tripterygium wilfordii. The enzyme-catalyzed conversions of the substrate, isotriptophenolide (12), afford a series of novel diterpene analogues to be evaluated in pharmacological screening programs as antineoplastic and immunosuppressive agents. Of particular interest are the quinone epoxides (14) and (15) for comparison with the highly active diterpene triepoxides, triptolide and tripdiolide. Some screening data obtained with the latter compounds and relating to their anticancer and immunosuppressive activity are also presented.

■ Rearrangement-Ring Expansion Reaction of Functionalized Cyclic Ethers. Stereoselective Synthesis of the ST- and XY-Ring Systems of Maitotoxin

Kazuo Nagasawa, Nobuyuki Hori, Ryuichi Shiba, and Tadashi Nakata*

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

Abstract

The rearrangement of 6-membered ethers having olefinic functional groups on the C2-side chain with Zn(OAc)₂ proceeded smoothly with ring expansion to give the 7-membered ethers. The 5,7-membered ether, prepared from the 7-membered ether, was again subjected to the rearrangement-ring expansion reaction to give the 6,7-membered ether, corresponding to the ST- and XY-ring systems of maitotoxin.

■ A Novel Synthesis of 1,2-Dehydro-1-aminophosphonates via Beckmann Rearrangement. Application to the Synthesis of a-Aminophosphonic Acid Derivatives

Tsutomu Yokomatsu, Takayuki Minowa, Yoshinori Yoshida, and Shiroshi Shibuya*

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

Abstract

Beckmann rearrangement of oxime mesylates (6a,b and 6d) mediated by TiCl₄, in the presence of (EtO)₃P gave the 1,2-dehydro-1-aminophosphonates (7a,b and 7d) in good yield. The utility of 7a,b was illustrated by a synthesis of α-aminophosphonates (11) and (12).

■ Synthesis and Central Nervous System Stimulant Activity of Camphor-1,2,4-triazines Fused with 1,2,4-Triazolo, Tetrazolo and 1,2,4-Triazine

Shin-ichi Nagai, Taisei Ueda, Akito Nagatsu, Nobutoshi Murakami, and Jinsaku Sakakibara*

*Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan

Abstract

Camphor-1,2,4-triazines fused with 1,2,4-triazole(3-9), tetrazole(10) and 1,2,4-triazine(11), were synthesized starting with (5R,8S)-3-hydrazino-5,9,9-trimethyl-5,6,7,8-tetrahydro-5,8-methano-1,2,4-benzotriazine(2). Compounds(2,3 and 10) showed central nervous system (CNS) stimulant activities.

■ New Synthetic Access to 1,3-Diaza-5-sila-2-boracyclohexane Frameworks by the Reaction of Borane with Bis[(N-arylimino)organosilylmethyl]silanes

Michinori Suginome, Masahiro Murakami, and Yoshihiko Ito*

*Departmene of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyou-ku, Kyoto 606-8501, Japan

Abstract

trans-4,6-Bis(organosilyl)-1,3-diaryl-1,3-diaza-5-sila-2-boracyclohexane derivatives were synthesized by the reaction of borane with bis[(N-arylimino)(organosilyl)methyl]silanes which were prepared by palladiumcatalyzed insertion of aryl isocyanides into the all Si-Si bonds of trisilane and tetrasilane.

■ A Novel Route to Diverse Fused Oxabicyclo[3.2.1]octanes –- A Ring Modified Trichothecanes

Hideo Nemoto, Junji Miyata, and Keiichiro Fukumoto*

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

Abstract

The novel A-ring modified trichothecane type of compounds (9a, b, 11, 13, 14a, b, 15a, b, and 16a, b), were synthesized starting from the A-ring aromatic diol (6).

■ A New Enantiocontrolled Route to (-)-Kainic Acid

Mitsuhiro Kawamura and Kunio Ogasawara*

*Pharnaceutical Institute, Tohoku University, Aramaki, Aoba-ku, sendai 980-8578, Japan

Abstract

A new route to (—)-kainic acid, the parent member of the kainoids, has been developed using (+)-norcamphor as the starting material.

■ A Facile Synthesis of 2-Acylimino-3-biphenylmethyl-1,3,4-thiadiazoline Derivatives

Terukage Hirata, Motoo Shiro, and Yoshimitsu Nagao*

*Faculty of Pharmaceutical Sciences, University of Tokushima, Sho-machi, Tokushima 770-8505, Japan

Abstract

Regioselective biphenylmethylation of 2-hifluoroacetamido-1,3,4-thiadiazole (3b) gave 2-trifluoroacetylimino-1,3,4-thiadiazoline derivatives (4c,d) in good yields. Compound (4d) was converted to 2-(2-chlorobenzoyl)imino-1,3,4-thiadiazoline derivative (6), an angiotensin II receptor antagonist. This methodology was also applied to the preparation of 2-acylimino-1,3,4-oxadiazoline derivative (8).

■ 6-Acetyl-8-hydroxy-2,2-dimethylchromene, an Antioxidant in Sunflower Seeds; Its Isolation and Synthesis and Antioxidant Activity of Its Derivatives

Hideyuki Tsuda, Youichi Ishitani, Yoshiyuki Takemura, Yoshiaki Suzuki, and Tadahiro Kato*

*Department of Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka 1-3, Shinjuku-ku, Tokyo 162-8601, Japan

Abstract

By the guide of assay toward inhibition of photooxidation of β-carotene, 6-acetyl-8-hydroxy-2,2-dimethylchromene (1) was isolated from sunflower seeds. In addition to 1, the analogous compounds possessing the chromene (chromane) skeleton were synthesized and their antioxidant activities were examined.

■ Synthetic Studies of Forskolin. A Diels-Alder Approach to Corey's Endoperoxide

Hsing-Jang Liu* and Xiao Shang

*Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada

Abstract

An alternative synthesis of Corey’s endoperoxide intermediate (2) leading to forskolin (1) has been effected via a Diels-Alder approach. An interesting feature is the unusual dehydrogenation process 12→13 which accompanied the reduction of the mesylate group with zinc and sodium iodide.

■ A Novel Reaction of an Overcrowded Germylene with Isothiocyanate Leading to the Formation of 4-Imino-1,3,2-dithiagermetane Ring System

Norihiro Tokitoh,* Kuniyuki Kishikawa, Kyoko Manmaru, and Renji Okazaki*

*Department of Chemistry, Graduate School of Science, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8567, Japan

Abstract

A diarylgermylene [Tbt(Tip)Ge:] kinetically stabilized by 2,4,6-tris-[bis(trimethylsilyl)methyl]phenyl (Tbt) and 2,4,6-triisopropylphenyl (Tip) groups was allowed to react with phenyl isothiocyanate to afford a germanium-containing four-membered heterocycle, 4-imino-1,3,2-dithiagermetane derivative via [2+2]cycloaddition reaction of initially formed diarylgermanethione [Tbt(Tip)Ge=S], the intermediacy of which was evidenced by electronic spetroscopy.

■ A New Synthesis of 1-Hydroxyindoles and Spectra of 1-Hydroxyindole

Toshiyuki Henmi, Takeshi Sakamoto, and Yasuo Kikugawa*

*Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan

Abstract

Partial reduction of 1-[2-(trimethylsilyl)ethoxy]-2-oxindole (3) with AlH(iso-Bu)₂ (DIBAL) and subsequent removal of the protecting group with (n-Bu)₄NF affords 1-hydroxyindole (1) in sufficiently pure form to produce reliable spectral data (nmr, ms, and uv) for the first time; this methodology is applicable to the synthesis of other 1-hydroxyindoles.

■ Synthesis of a Covalently Linked Bacteriopyropheophorbide — Pyropheophorbide Hybrid Dimer

Atsuhiro Osuka,* Yukihisa Wada, Kazuhiro Maruyama, and Hitoshi Tamiaki

*Department of Chemistry, Gradauate Schol of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan

Abstract

A covalently-linked bacteriopyropheophorbide α-pyropheophorbide α hybrid dimer was prepared. In this molecule, singlet energy transfer takes place from the pyropheophorbide to the bacteriopyropheophorbide subunit.

■ Reduction of Indigo: Simple Syntheses of 3-Acetoxy-, 1-Acetyl-2,3-dihydro-, 3-Acetoxy-3'-acetyl-, 3-Acetoxy-1,3'-diacetyl-2,2'-bisindoles, and 2,2'-Bisindole

Masanori Somei,* Hiroyuki Hayashi, and Shinobu Ohmoto

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

Abstract

Indigo was converted to 2,2’-bisindole by the direct reduction with zinc in acetic acid and acetic anhydride under argon or hydrogen atmosphere. Reduction with tin and iron afforded 3-acetoxy-2,2’-bisindole predominantly. Useful building blocks such as 1-acetyl-2,3-dihydro-, 3-acetoxy-3’-acetyl-, and 3-acetoxy-1,3’-diacetyl-2,2’-bisindoles were also produced depending on metal and reaction conditions.

■ Synthesis and Structures of Bis[N,N'-bis(trimethylsilyl)-2-methyl-1,3,2-diazasilacyclopentane] and Bis(N-trimethylsilyl-2-methyl-4,5-benzo-1,3,2-diazasilacyclopentene)

Nami Choi, Kumiko Asano, and Wataru Ando*

*Department of Chemistry, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki, 305-8571, Japan

Abstract

The reaction of 1,2-dimethyl-1,1,2,2-tetrachlorodisilane with N, N’-bis(trimethylsilyl)-ethylenediamine and -o-phenylenediamine in the presence ol triethylamine yielded bis(2-silaimidazolidine) (3) and bis(2-silaimidazoline) (4) derivatives in 38 and 61% yields, respectively. The structures of 3 and 4 were determined by the X-ray analyses.

■ New Sulfur-Carbon Displacement Reaction and Systematic Desulfurization in Multi-Sulfur Linkages of Benzopentathiepin

Satoshi Ogawa, Makoto Wagatsuma, and Ryu Sato*

*Department of Applied Chemistry, Faculty of Engineering, Iwate University, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan

Abstract

Benzopentathiepin reacts with phosphorus ylides to form a mixture of benzotetrathiepins and benzotrithiins. The carbanion fragment of the phosphorus ylides replaces the one or two sulfur atoms in the multi-sulfur linkages of benzopentathiepin. Systematic desulfurization to form a new cyclic system is accomplished by the use of a combination of phosphorus ylide and triphenylphosphine in the reactions of benzopentathiepin, benzotetrathiepins, and benzotrithiins.

■ A Secure and Convenient Synthesis of 5-Amino-1,2,3-thiadiazole by Diazoacetonitrile

Katsumasa Harada,* Yoshikatsu Mori, and Mamoru Nakai

*Ube Research Laboratory, UBE Indusries, Ltd., 1978-5 Kogushi, Ube Yamaguchi 755, Japan

Abstract

A new synthesis of 5-amino-1,2,3-thiadiazole (3) by diazoacetonitrile (2) and H₂S in the presence of a base is described. The compound (2) is undoubtedly explosive but with our method we found it could be used for industrial purposes.

■ Synthesis of Tetrahydro-1-benzazocin-2(1H)-ones Using 8-endo-trig Radical Cyclization of 2,2-Bis(phenylthio)-N-[o-(prop-2-enyl)phenyl]acetamides

Masazumi Ikeda,* Ken-ichi Obata, Jun-ichiro Oka, Hiroyuki Ishibashi, and Tatsunori Sato

*Kyoto Pharmaceutical University, Misasagi-Shichonocho, Yamashina, Kyorto 607-8414, Japan

Abstract

The effects of N-substituents upon the 8-endo-trig radical cyclization of 2,2-bis(phenylthio)-N-[o-(prop-2-enyl)phenyl]acetamides (4) were examined. The N-(p-methoxybenzyl) (4a) and N-tosyl derivatives (4b), when treated with tributyltin hydride in the presence of a small amount of azoisobutyronitrile, gave regioselectively the corresponding 3,4,5,6-tetrahydro-3-phenylthio-1-benzazocin-2(1H)-ones (5a,b) (8-endo cyclization products) in 40 and 47% yields, respectively, while the N-unsubstituted derivative (4c) afforded the reduction products (6c) and (8) as the major products. Some chemical transformation reactions of 5a are also described.

■ Practical Synthesis of (S)-3-(p-Nitrobenzyloxycarbonylamino)pyrrolidine and Its Related Compounds from L-Aspartic Acid

Hiroshi Tomori, Kuniko Shibutani, and Katsuyuki Ogura*

*Department of Applied Chemistry, Faculty of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

An efficient method for the preparation of (S)-3-aminopyrrolidine derivatives was developed starting from L-aspartic acid, which involves an efficient formation of a pyrrolidine-ring from allylamine and a practical Pd/C-catalyzed cleavage of N-allyl protective group. This method affords the enantiomerically pure desired compounds (1) in high overall yields.

■ Synthesis of Indolizidine Derivatives Trifluoromethylated at Bridgehead Position via Acyl Iminium Ion Intermediates Derived from Ring-Chain Tautomerism of 5,5,5-Trifluoro-4-oxopentanoyl Arylethylamides

Takashi Okano, Tsutomu Sakaida, and Shoji Eguchi*

*Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan

Abstract

Acyliminium ion intermediates were generated from the stable cyclic form of 5,5,5-trifluoro- 4- oxopentanoyl arylethylamides via acid catalyzed dehydration. Electrophilic cyclization of aryl group led to fused indolizidinones.