HETEROCYCLES

■ Some New Synthetic Approaches for the Preparation of Pteridine-3-oxides and Pteridines

Marjan Kocevar, Branko Stanovnik, and Miha Tisler

*Department of Chemistry and Chemical Technology, E. Kardelj University, Murnikova 6, 61000 Ljubljana, Slovenia

Abstract

Starting from 2-amino-3-cyanopyrazine some new syntheses of 4-substituted pteridines and pteridine-3-oxides have been devised.

■ An Efficient Method for C₈-N Bond Cleavage of Tetrahydroprotoberines Using Ethyl Chloroformate

Miyoji Hanaoka,* Kazuyoshi Nagami, Sanae Horima, and Takeshi Imanishi

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

Abstract

Ethyl chloroformate was found to be an effective reagent for C₈-N bond cleavage of tetrahydroprotoberberines having a trans-quinolizidine conformation. And some tetrahydroprotoberberines having a cis-conformation resulted in exclusive C₆-N bond cleavage on treatment with this reagent.

■ Efficient Synthesis of 3-Formyl-1,2,4-triazole Nucleoside Using Diethoxyacetonitrile as a Synthon

Teiichi Murakami, Masami Otsuka, Susumu Kobayashi, and Masaji Ohno*

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

Abstract

Diethoxyacetonitrile has been shown to be an efficient and versatile synthon for the synthesis of 1,2,4-triazole heterocycle (5), and 1-β-D-ribofuranosyl-1,2,4-triazole-3-carboxaldehyde (10) has been synthesized regiospecifically for the nitrogens and stereospecifically for the ribosylation.

■ A One-step Synthesis of 17α-Hydroxy Cardenolides and lsocardenolides from C₁₇ Steroidal Ketones

Rinaldo Marini-Bettolo, Connie S. J. Tsai, Thomas Y. R. Tsai, and Karel Wiesner*

*Institut für Pharmazeutische und Medizinische Chemie, Universität Münster, Hittorfstraβe 58-62, D-48149 Münster, Germany

Abstract

The steroidal ketone (3) gave in high yield the cardenolide (4) and iso-cardenolide (6) by treatment with the lithium derivatives prepared from 4-bromo- and 3-bromo-2-trimethylsilyloxyfuran, respectively.

■ A Synthesis of Pandaca Alkaloids, 20αH -Dihydrocleavamine and 20βH -Dihydrocleavamine

Seiichi Takano,* Masahiro Yonaga, Shin’ichi Yamada, Susumi Hatakeyama, and Kunio Ogasawara

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

Abstract

Alkaloids of Pandaca eusepala, 20αH-dihydrocleavamine and 20βH-dihydrocleavamine, have been synthesized in dl form using a α-diketone monothioketal intermediate.

■ Viscosalactone A and Viscosalactone B, Two New Steroidal Lactones from Physalis viscosa

S. William Pelletier, Gulilat Gebeyehu, Jacek Nowacki, and Naresh V. Mody

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

Abstract

Investigation of the extracts of Physalis viscosa has led to the isolation and structure elucidation of two new steroidal lactones, viscosalactone A (2) and viscosalactone B (3). The structures of these withanolides were assigned on the basis of chemical correlation with withaferin A and their ¹³C NMR spectral data.

■ Stereocontrolled Entry to Pyrimidine Hamamelo-C -nucleosides

T. Sato, H. Kobayashi, and R. Noyori*

*Department of Chmistry, Graduate School of Science, Nagoya University, Chikusa, Nagoya, Aichi 464-8601, Japan

Abstract

The reductive [3 + 4] cyclocoupling reaction of α,α,α’,α’-tetrabromoacetone and a furan has been applied to the first synthesis of hamamelo-C-nucleosides.

■ Lewis Acid Induced Electrophilic Substitution of Indole : Part 3

Julie Banerji,* Mrs. Asima Chatterjee,* Sukumar Manna, Claudine Pascard, Thierry Prange, and James N. Shoolery

*Laboratorio Central de Química, Universidad Técnica del Estado, Santiago 2, Chile

■ Total Synthesis of Furanoeremophilanes : (±)-Decompositin and the Related Natural Products

Koji Yamakawa and Tsuyoshi Satoh

*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan

Abstract

Total synthesis of furanoeremophilanes, (±)-6β-hydroxy-1,10-dehydrofuranoeremophilan-9-one (1a), (±)-decompositin (1b), (±)-adenostylone (1c) , (±)-dihydrodecompositin (16) , and (±)-3β,6β-dipropionyloxyeuryopsin-9-one (2), starting from the diene adduct (3) are described. An angular hydroxylation of 10H-furanoeremophilan-9-one derivatives is a key step in these total synthesis.

■ A Conversion of [1,2,5]-Oxadiazolo [3,4-d ]pyrimidine 1-Oxides into Purines

Fumio Yoneda,* Takao Tachibana, Junko Tanoue, Tetsumi Yano, and Yoshiharu Sakuma

*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan

Abstract

Treatment of [1,2,5]oxadiazolo[3,4-d]pyrimidine 1-oxides with amines led to the formation of the corresponding 8-substituted purine derivatives, along with other heterocyclic compounds in some cases.

■ Synthesis of Se⁸,2’-Cyclo-8-seleno-9-β -D-arabinofuranosyladenine : A Novel Purine Cyclonucleoside with a Selenium-bridge

Dean S. Wise, Jr., George H. Milne and Leroy B. Townsend*

*Department of Medical Chemistry, College of Pharmacy, University of Michigan , 930 North University, Ann Arbor, MI 48109-1055, U.S.A.

Abstract

The synthesis of 8-selenoadenosine (2) and Se⁸,2’-cyclo-8-seleno-β-D-arabinofuranosyladenine (3) are described. This synthesis of 3 involved the first use of 2-acetoxyisobutyryl chloride for the preparation of a purine cyclonucleoside.

■ Syntheses of Aminocyclitols and Aminocyclitol-Oligoglycosides from Uronic Acids and Glucuronide-Saponins by Means of Electrolytic Decarboxylation Reaction

Isao Kitagawa,* Toshiyuki Kamigauchi, Kiyoharu Shirakawa, Yoshiharu Ikeda, Hidenobu Ohmori, and Masayuki Yoshikawa

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

Abstract

By use of the electrolytic decarboxylation reaction as the key step, aminocyclitols (6b, 7b, 8b, 10b, 14b) and aminocyclitol-oligoglycosides (e.g. 18) have been conveniently synthesized from uronic acids (1, 9, 12) and glucuronide-saponins (e.g. 15). The conversions include the first syntheses of optically active D-neo- and L-neo-nitrocyclitols (10, 14).

■ Elaeodendroside D, E, H, I and J : New Cardiac Steroids from Elaeodendron glaucum

Kazutake Shimada, Tomoko Kyuno and Toshio Nambara, and Itsuo Uchida

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

Abstract

Five new cardiac glycosides having an unusual sugar linkage, elaeodendroside D, E, H, I and J, were isolated from seeds of Elaeodendron glaucum Pers. and their structures were assigned on the basis of chemical correlation with elaeodendroside A, respectively. An improved procedure for cleavage of a glycoside having a doubly linked sugar was applied to characterization of elaeodendroside B and C. The probable structures of these two stereoisomers were proposed.

■ 2-Oxazolines from Amides via Imidates

A. I. Meyers,* Mary Ann Hanagan, and Arthur L. Mazzu

*Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, U.S.A.

Abstract

Chiral oxazolines useful in asymmetric synthesis of o-substituted phthalides and benzoic acids are readily prepared from the benzamides via their imino ethers.

■ Synthesis of Imidazolopyridine Derivatives by an Unusual Reaction of N -Benzylpicolinamides with Phosphorus Pentachloride

Ryuji Tachikawa, Shigeru Tanaka and Atsusuke Terada*

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

Abstract

Reaction of N-benzylpicolinamides (1) with phosphorus pentachloride in the presence of pyridine gave rise to 3-phenylimidazolo[3,4-a]pyridines (2). Based on the reaction with N-benzyl-d₇-picolinamide, a possible mechanism for the formation of 2 is proposed.

■ Pericyclic Reaction of Oxepin with 3,4-Diazacyclopentadienone as an Electron-accepting Heterodienone System

Takashi Ban 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 cycloaddition reaction of oxepin with 2,5-diphenyl-3,4-diazacyclopentadienone prepared in situ from thermolysis of 1,3-bisdiazo-1,3-diphenyl-2-propanone gave anti-endo [4+2]π cycloadduct, which was found in the existence of equilibrium with the Claisen rearrangement product in solution by ¹H-NMR inspection.

■ A Facile Stereoselective Synthesis of (±)-Sesbanine

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

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

Abstract

10-Dehydrosesbanine (4), prepared via a sequence in which the tricyclic spiro cyclopentano-2,7-naphthyridine ring system is prepared by condensation of 3-(ethylenedioxy)cyclopentanecarboxylate ester anion with N-benzylnicotinamide, is stereoselectively reduced to a mixture of (±)-Sesbanine and (±)-10-epi-Sesbanine (6:1).

■ Cleavage of 4-Pyridylglycine Derivatives by Ni(II)-Phthalocyanine Catalysed Autoxidation-Model Experiments for Peptide Segment Coupling by Four Component Condensations

P. Bukall and I. Ugi*

*Institute of Chemistry, Academy of Sciences of the Moldavian SSR, Kishinev, U.S.S.R.

Abstract

The four component condensation of 4-pyridinecarboxaldehyde and aliphatic isonitriles with suitable protected α-amino acid derivatives yields products which can be cleaved by oxygen in the presence of nickel(II)-phthalocyanine into elongated peptide derivatives.

■ Amino- and Thiomethylenation of Maleimides

Rudolph A. Abramovitch* and Lubomir Floch

*Department of Chemistry, Clemson University, Clemson, SC 29631, U.S.A.

Abstract

Reaction of pyridinium p-toluenesulfonylmethylide with N-substituted maleimides in the presence of primary or secondary amines gives aminomethylenesuccinimides (4). The geometry of these enamines is presented. In one case, the E- and Z-isomers have been separated and characterized. The NMR spectra of the geometrical isomers is discussed. When thiophenol is used as the nucleophile a small yield of the phenylthiomethylenesuccinimide is obtained, but nucleophilic addition of the thiol to the maleimide takes place.

■ Synthesis of Deoxyribooligonucleotides by Using Aromatic Phosphoramidates as the Protecting Group for the 3’-Phospho Ends

Eiko Ohtsuka, Susumu Shibahara, Teiichi Ono, Toshikazu Fukui and Morio Ikehara

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

Abstract

p-Chlorophenylphosphoranilido chloridate was used to phosphorylate the 3’-hydroxyl groups of N,5’-O-protected deoxyribonucleosides. These nucleotides served as the 3’-terminal unit in the syntheses of some protected oligonucleotides which were used in a block condensation after removal of the anilido groups by treatment with isoamyl nitrite. Using this procedure, deoxyribooligonucleotides e. g. a decanucleotide containing a restriction endonuclease recognition sequence were synthesized.

■ Studies on Ketene and Its Derivatives. CIII. Synthesis of Fused 4-Pyrimidones and Their Photoreactions

Tetsuzo Kato,* Nobuya Katagiri, Uichiro Izumi, and Yutaka Miura, Takao Yamazaki, and Yoshiro Hirai

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

Abstract

The reaction of diketene with 2-amino-2-thiazoline (1a), 2-amino-5,6-dihydro-4H-1,3-thiazine (1b) and 2-amino-4,5,6,7-tetrahydro-1,3-thiazepine (1c) gave rise to 7-methyl-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidin-5-one (3a), 8-methyl-3,4-dihydro-2H,6H-pyrimido[2,1-b][1.3]thiazin-6-one (3b), and 9-methyl-2,3,4,5-tetrahydro-7H-pyrimido[2,1-b][1.3]thiazepin-7-one (3c), respectively. Photolysis of 3b in methanol gave 7-(1-aminoethylidene)-6-methoxy-8-oxo-1-thia-5-azabicyclo[4.2.0]octane (5). However, similar photolysis of 3c did not afford the β-lactam (7), but methyl 3-amino-2-[4,5,6,7-tetrahydro-2-(1,3-thiazepinyl)]crotonate (8).

■ Structure of Ezochasmanine, Ezochasmaconitine, Anisoezochasmaconitine and Synthesis of Vilmorrianine A

Hiromitsu Takayama, Miyuki Ito, Miyuki Koga, Shin-ichiro Sakai,* and Toshihiko Okamoto

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

Abstract

The structures of new diterpene alkaloids, ezochasmanine, ezochasmaconitine, and anisoezochasmaconitine, have been established as 3-hydroxychasmanine, 14-acetyl-8-benzoylchasmanine, and 14-acetyl-8-anisoylchasmanine respectively, in correlation with a known alkaloid chasmanine.
Vilmorrianine A (8-acetyl-14-anisoylezochasmanine) was synthesized from ezochasmanine via benzoylation, trichloroethoxycarbonylation, acetylation and elimination reaction of trichloroethoxycarbonyl group.

■ Convenient Synthesis of 3’-Substituted Methyl 7α -Methoxy-1-oxacephems

Tsutomu Aoki, Mitsuru Yoshioka, Susumu Kamata, Toshiro Konoike, Nobuhiro Haga, and Wataru Nagata*

*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan

Abstract

A convenient synthesis of the title compounds 1 is achieved by formation of glycols 3, 12, 13 and 14 or chlorohydrins 6 from epi-oxazolines having pertinent allylic substituents, followed by stereoselective, intramolecular etherification to 4, 7, 15, 16 and 17, elimination to 5, 18 and 19, and further conversions.

■ Functionalization of C-6 Position of Indolines

Mineo Fukui, Yoichi Yamada, Ayako Asakura, and Takeshi Oishi*

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

Abstract

Lithiation of π-(N-t-butyldimethylsilylindolines)chromium tricarbonyl by n-BuLi in the presence of TMEDA followed by the addition of aldehydes produced 4-, 5-, and 6-substituted indolines, the last ones being major products. 5- and 6-methoxyindolines were obtained from the corresponding addition products.

■ Synthesis of 11-phenyl-5,6-dihydro-11H -dibenz(b,e)azepine Derivatives

Kazuyuki Sasakura and Tsutomu Sugasawa*

*Shionogi Research Laboratories, Shionogi & Co. Ltd., Fukushima-ku, Osaka 553-0002, Japan

Abstract

A simple synthesis of a new type of dibenz(b,e)azepine having basic side chain 4 is described.

■ Studies in 1,3-Benzoxazines IV. Reaction of Imidoyl Chlorides of 1,3-Benzoxazines with Sulfoxides

Ryuji Tachikawa,* Kazuyuki Wachi and Atsusuke Terada

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

Abstract

The reaction of imidoyl chloride (1) with DMSO at room temperature gave rise to dimeric compound (3) as the main product besides hydroxymethyl compound (2), oxidized compound (4) and paraformaldehyde (5). On the other hand, the reaction was carried out at 85°C to give a different type product (9) involving ketal exchange reaction. When dibenzyl sulfoxide was used instead of DMSO, dimethyl ketal exchange product (10) was obtained together with benzaldehyde (11).

■ A Practical Route to Spiro-type Heterocycles Related to Erythrinan

Yoshisuke Tsuda,* Yuki Sakai, Mari Kaneko, Yukie Ishiguro, Kimiaki Isobe, Jun-ichi Taga, and Takehiro Sano

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

Abstract

A new method of synthesizing spiro-type heterocycles by intramolecular cyclization of 3,3-disubstituted dioxopyrrolines was presented. The method is particularly useful in synthesizing erythrinans and has the following advantages: 1) it is of short steps with high yield (one-pot reaction is possible), 2) an activating group at ring A is not necessary, and 3) the procedure can be carried out without protection of phenolic hydroxyl groups. Wide applicability of this method was also shown by synthesizing C-nor and C-homoerythrinans, and other variants which carry heterocycles at ring A instead of benzenoids.

■ Pteridines, LXX- Synthesis and Properties of 1,8-Alkylene-bridged Lumazines

Eugen Uhlmann and Wolfgang Pfleiderer

*Fakultät für Chemie, Universität Konstanz, Posttach 5560, D-7750 Konstantz, Germany

Abstract

A new type of lumazine derivatives (24-30) with a 1,8-alkylene bridge has been synthesized to study the protonation site in lumazine (1) itself. Comparisons of UV-data, however, do not allow a clear decision in this respect but indicate possibly the presence of a mixture of at least two cationic species. The structures of the newly synthesized compounds have been proven by UV- and NMR-spectra as well as pK_a measurements and elementary analyses. 8-β-Hydroxyethyl-7-oxo-7,8-dihydrolumazines (15-17) show an easy cyclization to the corresponding 1,8-ethano-bridged derivatives 18-20 on boiling with DMF.

■ Seven-carbon Annelation Synthesis of Substituted Spirochromans (3,4-Dihydro-spiro-[2H -1-benzopyran-2,1’-cycloheptanes])

P. Canonne,* D. Bélanger and G. Lemay

*Département de Chimie, Faculté des Sciences et de Génie, Université Laval, Cité Universitaire, Québec, G1K 7P4, Canada

Abstract

The use of 1,6-di(bromomagnesio)hexane in tetrahydrofuran leads after double addition at the carbonyl of substituted chromans to the formation of seven membered dihydroxycompounds. Subsequently the title compounds are formed by simple treatment with dilute acid and distillation.

■ Propellanes LVIII. Attempted Preparation of 11, 13-Dioxo-12-t -butyl-12-aza-[4.4.3]propella-2,4,7,9-tetraene

Michael Peled, Jacob Kalo and Devid Ginsburg*

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

Abstract

The title compound could not be prepared via intermediates having a dienic oxidation state nor via those with four double bonds as the latter rearrange during reaction.