HETEROCYCLES

■ Biographical Data

Shun-ichi Yamada*

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

■ Bibliography

Shun-ichi Yamada

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

■ Profesor Shun-ichi Yamada

Tohru Hino, Takayuki Shioiri, Shiro Ikegami, Kenji Koga, and Masakatsu Shibasaki

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

■ A New Synthesis of (-)-Aphanorphine by an Enantioconvergent Tactic

Masahiro Shimizu, Takashi Kamikubo, and Kunio Ogasawara*

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

Abstract

A new route to (-)-aphanorphine, isolated from the blue-green alga Aphanizomenon flos-aquae, has been devised by employing an enantioconvergent tactic making use of both enantiomeric starting materials.

■ An Enantioselective Synthesis of Natural (-)-Huperzine A via Cinchona Alkaloids-promoted Asymmetric Michael Reaction

Satoru Kaneko, Toshiharu Yoshino, Tadashi Katoh, and Shiro Terashima*

*Sagami Central Research Center, Hayakawa, Ayase, Kanagawa 252-1193, Japan

Abstract

An enantioselective synthesis of natural (-)-huperzine A (1) was achieved by a method featuring the Cinchona alkaloids-promoted asymmetric Michael reaction. Employing (-)-cinchonidine as a chiral catalyst, the asymmetric Michael reaction gave 64% ee of the product. The optically pure (+)-9 (>99% ee) obtained by recrystallization was convened to (-)-1.

■ A Ring-Expansion Route to Analogues of Dideoxyhydantocidin

Leo A. Paquette* and Carsten Behrens

*Evans Chemical Laboratories, The Ohio State University, 120 W. 18th Avenue, Columbus, Ohio 43210, U.S.A.

Abstract

The acid-catalyzed rearrangement of hydroxy β-lactam (12), formed by addition of the enantiopure dihydrofuranyllithium (10a) to N-benzyl-2,3-azetidinedione, has been investigated as a potential route to spirocyclic nucleosides.

■ New Entry to 1,4,5,6-Tetrahydro-2H-indol-2-ones Using a Cationic 5-endo-trigonal Cyclization onto Enamides

Hiroyuki Ishibashi,* Masahiro Higuchi, Hiromi Masuko, Kazuya Kodama, and Masazumi Ikeda

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

Abstract

A new method for the synthesis of 1,4,5,6-tetrahydro-2H-indol-2-ones by means of 5-endo-trigonal cyclization of α-thiocarbocations generated from sulfoxide (12) and α-chlorosulfide (17) is described. The sulfoxide (12). upon heating with TsOH, gave 14, which eliminated benzenethiol to give tetrahydroindolone (15). By contrast, the chlorosulfide (17), upon treatment with TiCl₄, gave the desulfurized tetrahydroindolone (18). The mechanism for the formation of 18 is also discussed.

■ Synthesis of New Methine Class of Dyes Bearing Maleimide Ring System

Yoshinori Tominaga,* Kaori Komiya, Sachiko Itonaga, Noriko Yoshioka, Seigo Kataoka, Kenji Sasaki, and Takashi Hirota

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

Abstract

Reaction of 1-methyl-3-methylthiomaleimides(1a-c) with N,N-dialkylanilines (2) under refluxing in acetic acid condition gave the corresponding 3-(4-diakylamino)phenyl-1-methylmaleimides (3a-g). Treatment of these 1-methyl-3-phenylmaleimides (3a,c) with Lawesson’s reagent under refluxing in toluene afforded new blue dyes, 4-(4-dialkylamino)phenyl-3-cyano-1-methyl-5-oxopyrrole-2-thiones(5a,b) which are brilliant blue dyes appearing at 606 and 615 nm (log ε: 4.59 and 4.50) in UV spectra. Reaction of 4-methoxycarbonyl-1-methyl-3-methylthiomaleimide (1b) with 3-dialkylaminophenol under the same reaction conditions gave cyclized products, 2H, 4H-[1]-benzopyrano[3,4-c]pyrrole-1,3,4-triones (6a-c) in good yields.

■ Synthesis of Both Enantiomers of Acetophthalidin

Hidenori Watanabe, Kanako Uchida, and Takeshi Kitahara*

*Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan

Abstract

Both enantiomers of acetophthalidin, a potent cell cycle inhibitor, were synthesized employing Sharpless asymmetric dihydroxylation as a key step.

■ Fusion of C₆₀ with Cyclic Amino Acid and Thiourea by Hetero Diels-Alder Reactions

Masatomi Ohno, Satoshi Kojima, Yuri Shirakawa, and Shoji Eguchi*

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

Abstract

C₆₀ underwent hetero Diels-Alder reaction with a carbethoxysubstituted 2-aza-1,3-butadiene and trimethylsilylthio-substituted 1,3-diaza-1,3-butadiene (which possibly reacts as trimethylsilylamino-substituted 1-thia-3-aza-1,3-butadiene) to give C₆₀ derivatives fused with cyclic amino acid and thiourea, respectively. The latter was explained to arise under equilibrated conditions.

■ Chiral Bidentate Lithium Amides Having a Chiral Amide Nitrogen for Enantioselective Deprotonation of 4-tert-Butylcyclohexanone

Haruko Chatani, Makoto Nakajima, Hisashi Kawasaki, and Kenji Koga*

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

Abstract

Enantioselective deprotonation of 4-tert-butylcyclohexanone (1) by chiral bidentate lithium amides ((R)-5a~b) was examined in the presence of excess TMSCI in several solvents containing 2 equivalents of HMPA. The sense of asymmetric induction was found to be the same with that by using (R)-2a~b. This result suggests the formation of a similar chiral amide nitrogen in these chiral lithium amides.

■ Total Synthesis of the Structure Proposed for Picrasidine-H (Dimeric 4-Methoxy-β-carboline Alkaloid)

Hideharu Suzuki, Yuki Ebihara, Yuusaku Yokoyama, and Yasuoki Murakami*

*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

Total synthesis of the reported structure of naturally occurring picrasidine-H (dimeric 4-methoxy-β-carboline alkaloid) was accomplished. However, the synthesized compound was not identical with the natural product. Our precise considerations revealed that the reported structure of picrasidine-H had been incorrectly characterized.

■ A Concise Synthesis of Arnottin I via Internal Biaryl Coupling Reaction Using Palladium Reagent

Takashi Harayama* and Hirotake Yasuda

*Faculty of Pharmaceutical Science, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan

Abstract

Total synthesis of arnottin I (1) was accomplished via the internal arylaryl coupling reaction of iodo-ester (2) by the palladium-assisted cyclization reaction.

■ Enantioselective Synthesis of Eucomols Using Sharpless Catalytic Asymmetric Dihydroxylation

Sang-sup Jew,* Hyun-ah Kim, Jeong-hoon Kim, and Hyeung-geun Park

*College of Pharmacy, Seoul National University, Shillim-Dong, San 56-1, Kwanak-Gu, Seoul 151-742, Korea

Abstract

A novel synthetic method was developed for eucomols, (S)-3-hydroxyhomoisoflavanones. Addition of aryllithium to aldehyde ((S)-9) obtained by asymmetric dihydroxylation of 4, followed by the formation of cyclic ether, gave eucomols, (S)-3-hydroxyhomoisoflavanones (1a-e).

■ Oxidation of Amines with Hypervalent tert-Butylperoxyiodanes: Synthesis of Imines and tert-Butylperoxyamino Acetals

Masahito Ochiai,* Daisuke Kajishima, and Takuya Sueda

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

Abstract

Reaction of secondary amines with 1-tert-butylperoxy-1,2-benziodoxol-3(1H)-one (2) undergoes dehydrogenation to afford imines in the presence of K₂CO₃, while oxidation of tertiary amines without base produces tert-butylperoxyamino acetals.

■ Chiral β-Amino Sulfoxides as Chiral Ligands in Palladium-catalyzed Asymmetric Allylations

Kunio Hiroi* and Yoshio Suzuki

*Department of Synthetic Organic Chemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

New chiral β-amino sulfoxide ligands bearing chiral sulfinyl functionality as a sole chiral source have been deviced and palladium-catalyzed asymmetric allylations of acetoacetate with these ligands have been examined. The highest enantioselectivity (50%) was observed with 5b. The participation of chual sulfinyl functionality to palladium catalysts is discussed on the basis of the stereochemical outcome obtained.

■ Reaction of Pyridazine and Quinoline with Silyl Enol Ethers in the Presence of Alkyl Chloroformate

Takashi Itoh, Michiko Miyazaki, Kazuhiro Nagata, and Akio Ohsawa*

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

Abstract

Pyridazine was allowed to react with silyl enol ethers (or ketene silyl acetals) in the presence of ethyl chloroformate to give 4- and 6-substituted 1-ethoxycarbonyldihydropyridazines in good yields. The vicinal substituents of silyl enol ethers considerably affected the regioselectivity, and one of the two dihydroadducts was selectively obtained by the use of appropriate silyl enol ethers. Similar substituent effect was observed in the reaction of quinolines under the same conditions.

■ A Short Path Synthesis of α-Hydroxy Ester from Aldehyde Using (1-Ethoxy-vinyl)lithium and Its Application to the Syntheses of Thymine Polyoxin C and Uracil Polyoxin C

Hiroyuki Akita,* Kimio Uchida, and Cheng Yu Chen

*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

A short path synthesis of the α-hydroxy esters (4 and 5) from the aldehyde (3) using (1-ethoxyvinyl)lithium and its application to the total syntheses of the pyrimidine nucleoside, thymine polyoxin C (1) and uracil polyoxin C (2), are described.

■ Syntheses of Serotonin, N-Methylserotonin, Bufotenine, and Melatonin, and the First Total Synthesis of N-(Indol-3-yl)methyl-N-methyl-5-methoxytryptamine from Tryptamine through a Common Intermediate, 1-Hydroxytryptamine

Masanori Somei,* Fumio Yamada, and Harunobu Morikawa

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

Abstract

Simple syntheses of serotonin (1a), N-methylserotonin (1b), bufotenine (1c), and melatonin (2), and the first total synthesis of N-(indol-3-yl)methyl-N-methyl-5-methoxytryptamine (3) from tryptamine (4a) are reported through acid catalyzed nucleophilic substitution reaction of 1-hydroxytryptamines.

■ 1,3-Dipolar Cycloadditions of α-Methoxy-carbonylnitrones in the Presence of Eu(fod)₃

Osamu Tamura,* Naka Mita, Kentoku Gotanda, Ken-ichi Yamada, Tsuyoshi Nakano, Ruriko Katagiri, and Masanori Sakamoto*

*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

1,3-Dipolar cycloadditions of α-methoxycarbonylnitrones (1) in the presence of Eu(fod)₃ were investigated. Treatment of the nitrones (1) with vinyl ethers (2) in the presence of Eu(fod)₃ caused intemolecular cycloaddition to give stereoselectively trans-adducts (trans-3). In contrast, the reactions of the nitrones (1) with allyl alcohols (4) under similar conditions induced transesterification and intramolecular cycloaddition to afford polycyclic products (5).

■ New Reactions of Phosgene with Tertiary Amines

Taisuke Itaya* and Tae Kanai

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

Abstract

1-Benzylwye (3) underwent substitution at the 7-position in the presence of COCl₂ and pyridine in THF to afford various products depending upon the post-treatment through 1,4-dihydropyridine (7) and carboxylic acid derivative (8). When Et₃N was used instead of pyridine, it reacted with COCl₂ to provide two enamines (18 and 19), together with diethylcarbamyl chloride (20), after treatment of the reaction mixture with MeOH.

■ An Alternative and Facile Synthesis of Pikronolide

Noriyuki Nakajima,* Makoto Ubukata, and Osamu Yonemitsu*

*Biotechnology Research Center, Toyama Parefectural University, 5180 Kurokawa, Kosugi, Toyama 939-0398

Abstract

An alternative and facile synthesis of pikronolide (2), the aglycon of pikromycin (1), via coupling between the C₁₁-C₁₅ fragment (10) and the C₁-C₁₀-fragment (12), Horner-Emmons cyclization, regioselective protection of the C₅-hydroxy group, and oxidution of the C₃-hydroxy group, is described. In this synthesis, the conformational analysis by NMR played an important role.

■ Chemoenzymatic Formal Synthesis of (-)-Indolmycin

Toshikazu Bando and Kozo Shishido*

*Institute for Medicinal Resources, University of Tokushima, Sho-machi, Tokushima 770-8505, Japan

Abstract

An enantioselective formal total synthesis of indolmycin (1) has been accomplished based on the lipase mediated asymmetric acetylation of the prochiral diol (5).

■ Synthesis and Facile Ring Opening of 2,3,4-Triphenyl-3-azabicyclo[3.2.0]hepta-1,4-diene

Kiyoshi Matsumoto,* Sadahiro Goto, Naoto Hayashi, and Takane Uchida

*Graduate School of Human and Environmental Studies, Kyoto University, Yoshida-Nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

The first synthesis of 2,3,4-triphenyl-3-azabicyclo[3.2.0]-hepta-1,4-diene (pyrrolocyclobutene) that has no substituent in the cyclobutene moiety, is described. This compound underwent an extremely facfle electrophilic attack at the β position to give the ring opened product.

■ A Versatile Approach for Functionalization of 3-Aryl-3-trifluoromethyldiazirine Photophor

Makoto Hashimoto, Yuichi Kanaoka, and Yasumaru Hatanaka*

*Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan

Abstract

We introduce here a novel and simple method for the carbonylation of (alkoxyphenyl)diazirine. 3-(3-Methoxyphenyl)-3-trifluoromethyldiazirine was found to be stable under a typical Friedel-Crafts reaction producing carboxaldehyde derivatives of methoxyphenyldiazirine. The formyl group was easily converted to carboxylic acid, olefin, alcohol, or benzyl bromide providing new derivatives of diazirine photophor in the field of photoaffinity labeling.

■ The First Total Synthesis of Floerkein B and Barbilycopodin

Nobuo Kato,* Atsushi Higo, Xue Wu, and Hitoshi Takeshita*

*Instituete of Advanced Material Study, Kyushu University, 6-1, Kasuga-koen, Kasuga 816-8580, Japan

Abstract

From functionalized iridoid and geranyl synthons, natural floerkein B and barbilycopodin, bicyclic diterpenoids containing an eleven-membered ring, have been totally synthesized via stereocontrolled Cope rearrangement of a dioxasilepine derivative.

■ A Simple and Convenient Synthetic Method for α-Trifluoromethylpyridines

Etsuji Okada,* Tatsuhiko Kinomura, Yukio Higashiyama, Hiroshi Takeuchi, and Masaru Hojo

*Department of Chemical Science andd Engineerring, Faculty of Engineering, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

β-Trifluoroacetylvinylamine (1) reacted easily with various active methylene compounds in the presence of trifluoroacetic acid under mild conditions to give α -trifluoromethylpyridines (2) in moderate to high yields.

■ A New Route for the Tricyclic Indole System: A Useful Intermediate for Ergot Alkaloids

Yuusaku Yokoyama,* Hiroaki Matsushima, Mitsuru Takashima, Tomoko Suzuki, and Yasuoki Murakami*

*School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

Cyclization of 4-bromoindole derivatives which have α,β-unsaturated esters or aldehydes in the C₃-side chain, were accomplished using intramolecular palladium-catalyzed cyclization (Heck reaction) or radical cyclization using Bu₃SnH and AIBN. A cyclohexa[c,d]indole system was formed by the radical reaction, while a cyclohepta[c,d]indole system was obtained using the Heck reaction.

■ Enantiocontrolled Synthesis of (11S,12S,13S)-(9Z,15Z)- and (11R,12S,13S)-(9Z,15Z)-11-Hydroxy-12,13-epoxy Octadecadienoic Acids by Means of the Sharpless Asymmetric Epoxidation of the Unsymmetrical Divinylcarbinol

Toshio Honda,* Mai Ohta, and Hirotake Mizutani

*Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

(11S,12S,13S)-(9Z,15Z)- and (11R,12S,13S)-(9Z,15Z)-11-Hydroxy-12,13-epoxy octadecadienoic acids, self defensive substances against the rice blast disease, were synthesized enantioselectively by employing the Sharpless asymmetric epoxidation reaction of the unsymmetrical divinylcarbinol, as a key step.

■ Photorearrangement of the ortho-Cycloadduct of 6-Chloro-1,3-dimethyluracil to Benzene through [π4s+π2a]Photocycloaddition

Kazue Ohkura, Yukari Noguchi, and Koh-ichi Seki*

*Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

Reaction pathway for the formation of the hydrogen chloride adducts of pyrimidosemibullvalene-2,4-dione derived from the photoreaction of 6-chloro-1,3-dimethyluracil in frozen benzene is interpreted by the mechanism involving the initial ortho-cycloaddition, not meta-cycloaddition, followed by the photochemical disrotatory cleavage of the cyclobutene moiety, and the successive intramolecular photo-Diels-Alder reaction of the resulting cyclooctatetraene ring.