Regular Issue

Vol. 43, No. 11, 1996

25 data found. 1 - 25 listed
Communication | Regular issue | Vol 43, No. 11, 1996, pp. 2325 - 2332
Published online:
DOI: 10.3987/COM-96-7569
Chimeric Azalides with Functionalized Western Portions

Sherman T. Waddell, Jeffrey M. Eckert, and Timothy A. Blizzard

*Merck Research Laboratories, 50G-231, P.O. Box 2000 Rahway, NJ 07065, U.S.A.


A series of chimeric azalides which are homologous to the potent azalide antibiotic 9-deoxo-8a-aza-8a-homoerythromycin A (2) in their easter halves, but which have functionally complex western halves derived from a variety of sources, including carbohydrates, is reported.

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Communication | Regular issue | Vol 43, No. 11, 1996, pp. 2333 - 2336
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DOI: 10.3987/COM-96-7588
A Novel Dimerization of 1-Hydroxyindoles

Masakazu Hasegawa, Mutsuko Tabata, Keiichi Satoh, Fumio Yamada, and Masanori Somei

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


1-Hydroxyindoles are sensitive to acids and undergo four types of competing reactions; dehydroxylation, nucleophillic substitution, dimerization, and formation od hexacyclic dimer. The direction of the reaction seems to be determined depending on the subtle balance of substrate structures, acids, and reaction conditions. Structures of variety of products are unequivocally determined by X-ray single crystallographic analyses and chemical correlations.

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Communication | Regular issue | Vol 43, No. 11, 1996, pp. 2337 - 2342
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DOI: 10.3987/COM-96-7594
Stereoselective Synthesis of 6α-Halopenicillanates by Samarium(II) Iodide-promoted Reduction of 6,6-Dihalopenicillanates

Han-Young Kang, Ae Nim Pae, Yong Seo Cho, Kyung II Choi, Hun Yeong Koh, and Bong Young Chung

*Department of Chemistry, Chonbuk National University, Dukjindong 664-14, Chonju, 561-756, Korea


A mild and efficient samarium(II) iodide promoted-reduction of 6,6-dibromopenicillanates for stereoselective synthesis of 6α-bromopenicillanates has been developed.

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Communication | Regular issue | Vol 43, No. 11, 1996, pp. 2343 - 2346
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DOI: 10.3987/COM-96-7596
Application of the Phthalimidine Synthesis with Use of 1,2,3-1H-Benzotriazole and 2-Mercaptoethanol as Dual Synthetic Auxiliaries. Part 1. A Simple Synthesis of (±)-Indoprofen

Ichiro Takahashi, Etsushi Hirano, Teruki Kawakami, and Hidehiko Kitajima

*Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Fukui University, Bunkyo, Fukui-Shi 910-8507, Japan


A representive nonsteroidal anti-inflammatory drug indoprofen is prepared in 4 steps from the commercially available 2-(4-nitrophenyl)propanoic acid. The key step is the mild phthalimidine synthesis by the double Mannich condensation of o-phthalaldehyde with ethyl 2-(4-aminophenyl)propanoate with use of 1,2,3-1H-benzotriazole and 2-Mercaptoethanol as dual synthetic auxiliareis.

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Communication | Regular issue | Vol 43, No. 11, 1996, pp. 2347 - 2351
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DOI: 10.3987/COM-96-7597
Unusual Enamide Cleavage of Frangufoline under Mild Acidic Condition

Dae-Yeon Suh, Yong Chul Kim, Yong Nam Han, and Byung Hoon Han

*Natural Products Research Institute, Seoul National University, 28, Yungun, Jongro Seoul 110-460, Korea


In mild acidic condition (2N HCl, 55 °C), frangufoline, a frangulanine type 14-membered cyclopeptide alkaloid was first converted via unusual enamide cleavage to sanjoinine-G2, which was further hydrolyzed to a linear compound, (S)-[(N’,N’)-dimethylphenylalanyl[-(2S,3S)-3-(p-formylphenoxyleucyl)-(S)-leucine. From the extensive acid hydrolysates, 4-hydroxybenzaldehyde was also isolated. Air oxidation of the vinylic double bond followed by the liberation of formaldehyde is proposed for a possible mechanism for the ring cleavage.

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Communication | Regular issue | Vol 43, No. 11, 1996, pp. 2353 - 2356
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DOI: 10.3987/COM-96-7604
A Short Three Components Approach to Fused Pyrrolo[2,3-b]pyrrolidinone

Yoshinari Okamoto, Tadashi Okawara, and Mitsuru Furukawa

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


4-Methyl-4-dimethoxymethylpyrans (5b) and (5c) prepared from 1,3-cyclohexanediones (2), pyruvaldehyde dimethyl acetal (3b), and malononitrile (4), were subjected to hydrolysis with HCl to give fused furofuranones (6), which were treated with amines to give fused pyrrolidinones (9).

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Communication | Regular issue | Vol 43, No. 11, 1996, pp. 2357 - 2360
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DOI: 10.3987/COM-96-7612
A Diastereoselective Synthesis of trans, trans-Octahydronaphthoquinolizine

Hai Mi and David I. Schuster

*Department of Chemistry, New York University, 31 Washington Place, New York, NY 10003, U.S.A.


A facile approach involving stereospecific reduction of an enamine moiety in a tetracyclic system has made it posible to synthesize diastereospecifically the biologically active octahydronaphthoquinolizine with trans, trans stereochemistry.

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Communication | Regular issue | Vol 43, No. 11, 1996, pp. 2361 - 2365
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DOI: 10.3987/COM-96-7616
The Reaction of Electron Excess Aromatic Heterocycle, 1,4-Dihydropyrrolo[3,2-b]pyrrole and Some Related Compounds with Chlorosulfonyl Isocyanate (CSI)

Kyosuke Satake, Kentaro Yano, Makoto Fujiwara, and Masaru Kimura

*Department of Chemistry, Faculty of Science, Okayama University, 3-1-1 Tsushima-naka, Okayama 700-8530, Japan


The reaction of 3,6-di-tert-butyl-1,4-dihydropyrrolo[3,2-b]pyrrole and its N,N’-dimethoxycarbonyl derivative with chlorosulfonyl isocyanate (CSI) was investigated. The higher reactivity for the electrophilic reaction and a remarkable electron excessiveness of the system were demonstrated by comparing with those of indole and pyrrole derivatives.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2367 - 2376
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DOI: 10.3987/COM-96-7524
Novel Bicyclic Phosphordiamidate HIV Protease Inhibitors

Joanne M. Smallheer and Steven P. Seitz

*The DuPont Merck Pharamceutical Co., Inc., WR 2117, P.O. Box 80722, Wilmington, DE 19880 - 0722, U.S.A.


Several substituted (3-endo,4-endo,6-exo)-8-oxa-7-diaza-1-phosphabicyclo[3.2.1]octanols were prepared and evaluated as inhibitors of HIV protase. This new bicyclic ring system is the product of an unexpected intramolecular cyclization observed upon base treament of a 4,5,6,7-hexahydro-5,6-bishydro-2-phenoxy-1H-1,3,2-diazaphosphepine-2-oxide. An exsample of this new class of compounds had subnanomolar activity vs. HIV protease and antiviral activity in a cell-based assay.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2377 - 2384
Published online:
DOI: 10.3987/COM-96-7526
Synthesis of Vinca Alkaloids and Related Compounds. Part LXXXII. An Unexpected Neber-Type Rearrangement

István Moldvai, Csaba Szántay Jr., and Csaba Szántay

*Central Research Institute for Chemistry, Hungarian Academy of Sciences, H-1525 Budapest, P.O.Box 17, Hungary


(+)-15-Oxo-14,15,-dihydroeburnamenine (2) was tansformed into oxime (3). On treatment with acetic acid or Raney Ni, oxime (3) afforded the 15-acetamidovincamone isomers (4,5) and the 15β-amino derivatives (12,13), respectively. The oxime acetate (14) and the oxime ether (15) were also prepared.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2385 - 2396
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DOI: 10.3987/COM-96-7549
Synthesis, Crystallographic Studies and Biological Evaluation of Some 2-Substituted 3-Indazolyl-4(3H)-quinazolinones and 3-Indazolyl-4(3H)-benzotriazinones

Giuseppe Daidone, Salvatore Plescia, Demetrio Raffa, Domenico Schillaci, Benedetta Maggio, Franco Benetollo, and Gabriella Bombieri

*Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi n 32 90123 Palermo, Italy


A number of new 3-(indazol-3 and 5-yl)-4(3H)-quinazolinone and 4(3H)-benzotriazinone derivatives were prepared by reaction of 3- or 5-(2-aminobenzamido)indazole with ethyl orthoesters and nitrous acid respectively. Structures were established on the basis of analytical and stpectroscopic data. Single-crystal X-ray analysis confirmed the quinazolinone structure of compounds (5). The 4(3H)-quinazolinones and 4(3H)-benzotriazinones were tested at 200 μg/ml for antimicrobial activity against C. albicans, C. tropicalis and S. aureus, at 100 μM for their antitumor effect on human-lymphoblast-like cells and finally at 500 μM for 3a-hydroxysteroid dehydrogenase (3α-HSD) inhibition.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2397 - 2407
Published online:
DOI: 10.3987/COM-96-7555
2-(Tosylamino)benzyltrimethylammonium Halides as Precursors of 2-Substituted Indoles

Piero Dalla Croce, Raffaella Ferraccioli, and Concetta La Rosa

*Centro C.N.R., Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, via Golgi 19, I-20133 Milano, Italy


The reactions of 2-(tosylamino)benzyltrimethylammonium halides (1) with dimethylsulfonium 2-oxo-2-phenylethylide (6b), dimethylsulfonium 2-ethoxy-2-oxo-ethylide (6c) and dimethylsulfonium cyanomethylide (6d) are useful synthetic routes to 2-substituted indoles (8b-d). The relationship between reaction conditions and selectivity is discussed.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2409 - 2413
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DOI: 10.3987/COM-96-7556
Ring Transformation of Cinnolines with Ynamines

Ken-ichi Iwamoto, Hiroyuki Fukuta, Sumiko Suzuki, Jyunko Maruyama, Etsuo Oishi, Akira Miyashita, and Takeo Higashino

*Schol of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan


Cinnolines having electron-withdrawing substituents at 4-position reacted with ynamines to give naphthalene derivatives and/or quinoline derivatives through [4+2] cycloaddition followed by elimination of nitrogen or hydrogen cyanide.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2415 - 2424
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DOI: 10.3987/COM-96-7563
Synthesis and Reactivity of a 3-Vinylidenepiperidine as a Model Study of α-Allenic Amines

Daniel Solé, Silvina Garcia-Rubio, Joan Bosch, and Josep Bonjoch

*Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Av. de Joan XXIII, s/n, 08028 Barcelona, Spain


4-Acetonyl-1-benzyl-3-vinylidenepiperidine (8), prepared by cyclization of Propargylic Silane (7), was used as a model to study the usefulness of the allene moiety as a precursor of the two-carbon chain present in the piperidine ring of Strychnos alkaloids.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2425 - 2434
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DOI: 10.3987/COM-96-7565
An Asymmetric Synthesis of 4-Aryl-1,4-dihydropyridines

Chen-Yu Cheng, Jy-Yih Chen, and Mei-Jing Lee

*Institute of Pharmaceutical Sciences, National Taiwan University, 1, Sec. 1, Jen-Ai Road, Taipei 10018, Taiwan, R.O.C.


Phenyllithium was found to attack preferenitally the ester group of 5-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-2,6-dimethylnicotinic acid ethyl ester (6) to give phenyl ketone (7) and diphenylcarbinol (8), despite the directing effect of the oxazoline group. By replacing the ethyl ester in 6 with a butyl tert-butyl ester, the desired 1,4-addition with PhLi to give 4-phenyldihydropyridine derivative (12) in 67% was observed. As a chiral version of the above reaction, 2-[5-(tert-butoxycarbonyl-2,6-dimethyl-3-pyridyl]-4-(S)-methoxymethyl-5-(S)-phenyl-δ2-oxazoline (13) reacted with PhLi to give 3-(tert-butoxycarbonyl)-2,6-dimethyl-N-ethoxycarbonyl-5-[(4S,5S)-4-methoxymethyl-5-phenyl-4,5-dihydro-oxazol-2-yl]-4-(S)-phenyl-1,4-dihydropyridine (1) and its C-4 epimer (2) in a ratio of 5:1 and a total yield of 54%.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2435 - 2441
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DOI: 10.3987/COM-96-7567
Synthesis of 3-Alkyl-4-aryl- and 3,4-Diaryl-1,2,5-thiadiazoles via Palladium-catalyzed Cross-Coupling Reaction

Yasuaki Hanasaki

*Tokyo Research Laboratory, Tosoh Corporation, 2743-1, Hayakawa, Ayase-shi, Kanagawa-ken 252, Japan


4-Substituted 3-aryl-1,2,5-thiadiazoles were synthesized by palladium-catalyzed cross-coupling reaction of aryldtannane with easily available 4-substituted 3-halogeno- and 3-trifluoromethylsulfonyloxy-1,2,5-thiadiazoles.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2443 - 2456
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DOI: 10.3987/COM-96-7568
Studies with Plant Cell Cultures of Cassia didymobotrya. VII. Enzyme Catalyzed Biotransformation of Dibenzylbutanolides to Podophyllotoxin Analogues and Related Compounds

Bruno Botta, Giuliano Delle Monache, Paola Ricciardi, Alberto Vitali, Vittorio Vinciguerra, Domenico Misiti, James P. Kutney, and Nikolay Stoynov

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


Enzyme-catalyzed cyclizations of synthetic dibenzylbutanolides to analogues of the podophyllotoxin family are described. The biotransformations utilize enzymes derived from Cassia didymobotrya cell cultures and previously synthesized debenzylbutanolides with differ in functionality in order to evaluate the course of the cyclization process. The application of this methodology provides additional informations relating to the utilization of such "substrates" in the future synthesis of the anti-cancer drug, Etoposide, via a combination of synthetic chemistry and biotechnological methods.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2457 - 2464
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DOI: 10.3987/COM-96-7571
Thermal Addition Reaction of Aroylketene with Ethyl Vinyl Ether: Aromatic Substituent Effect on Aroylketene Reactivity

Jun Toda, Toshiaki Saitoh, Taichi Oyama, Yoshie Horiguchi, and Takehiro Sano

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


A series of aroylketenes (2) generated by thermolysis of 5-aryl-2,3-dihydrofuran-2,3-diones (1) reacted with ethyl vinyl ether under a thermal condition to give 2,3-dihydro-4H-pyran-4-ones (3) and/or 4H-pyran-4-ones (4). In this reaction the electron withdrawing substituent (No2, Cl) introduces into the aryl part enhanced the ketene reactivity (2b-e), while the electron donating one (OMe) did not affect its reactivity (2f-g) in a significant extent. The heteroaroylketenes (2h) and (2i) showed a fairly good reactivity.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2465 - 2472
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DOI: 10.3987/COM-96-7572
Synthesis of 1-Aryl-3-phenylsulfonyl-1,2,4-triazoles from 1,5-Diaryl-3-phenylsulfonylformazans

Masahiko Takahashi and Sachio Ohnishi

*Department of Materials Sciences, Faculty of Engineering, Ibaraki University, 4-12-1 Nakanarusawamachi, Hitachi, Ibaraki 316-8511, Japan


1,5-Diaryl-3-phenylsulfonylformazans (5) were prepared through phenylsulfonylmethanal arylhydrazones (4) starting from methyl phenyl sulfone. Treatment of these formazans (5) with formalin and potassium hydrogen sulfate in DMF gave 1-aryl-3-phenylsulfonyl-1,2,4-triazoles (9) instead of the expected 1,5-diaryl-3-phenysulfonylverdazyls (8).

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2473 - 2482
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DOI: 10.3987/COM-96-7575
Ytterbium Triflate Catalyzed Ring Opening of Aziridines with Amines

Masaki Meguro and Yoshinori Yamamoto

*Department of Chemistry, Graduate School of Science, Tohoku University, Aobayama, Sendai 980-8578, Japan


Ring opening of aziridines with amines takes place readily in the presence of catalytic amounts of ytterbium triflate Yb(OTf)3, giving the corresponding 1,2-diamines regioselectively in good high yields.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2483 - 2486
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DOI: 10.3987/COM-96-7579
Two New Acridone Alkaloids from the Roots of Marsh Grapefruit

Yuko Takemura, Junko Takaya, Motoharu Ju-ichi, Mitsuo Omura, Chihiro Ito, and Hiroshi Furukawa

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


Two new acridone alkaloids, margrapine-A and -B were isolated from the roots of Marsh grapefruit (Citrus paradisi Macf.). Their structures were characterized on the basis of spectroscopic evidence.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2487 - 2493
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DOI: 10.3987/COM-96-7582
2:2 Condensation Products from the Reaction of N-Substituted 1,2-Diaminoethanes and 1,3-Diaminopropanes with Succinaldehyde and Glutaraldehyde

Tadashi Okawara, Yoshinari Okamoto, Shuji Ehara, Tetsuo Yamasaki, and Mitsuru Furukawa

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


The reaction of N-substituted 1,2-diaminoethanes and 1,3-diaminopropanes (1) with succinaldehyde (2) and glutaraldehyde (9) in water gave the 2:2 condensation products (4 and 10).

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2495 - 2502
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DOI: 10.3987/COM-96-7586
A New Synthetic Route to 6,7-Dichloro-5,8-quinoxalinedione and Synthesis of Its Derivatives

Gyoonhee Han, Kye Jung Shin, Dong Chan Kim, Kyung Ho Yoo, Dong Jin Kim, and Sang Woo Park

*Division of Applied Science, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, Korea


6,7-Dichloro-5,8-quinoxalinedione (2), an analogue of Dichlone®, was prepared from 4-aminophenol (3) in 27% overall yield in 8 steps via chloroxidation of the sulfuric acid salt of 8-amino-5-quinoxalinol (9) as a key step. And two derivatives, 6-chloro-5-hydroxypyrazino[2,3-a]phenazine (10) and pyrido[1,2-a]imidazo[4,5-g]quinoxaline-6,11-dione (11), were prepared by reaction of 2 with 1,2-phenylenediamine and 2-aminopyridine in 79% and 46% yields, respectively.

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Paper | Regular issue | Vol 43, No. 11, 1996, pp. 2503 - 2511
Published online:
DOI: 10.3987/COM-96-7615
Reaction of 3-Iodochromone with Nucleophile 1. Reaction of 3-Iodochromone with Azoles

Yoshiaki Sugita and Ichiro Yokoe

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


3-Iodochromone (1a) rected with azoles, such as imidazole and pyrazole to afford 2-(N-azolyl)chromones (2-7) under very mild conditions in high yields. In the case of indoles as the nucleophile, aurone derivatives (9) were obtained together with 2-(N-indolyl)chromones (8).

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Review | Regular issue | Vol 43, No. 11, 1996, pp. 2513 - 2522
Published online:
DOI: 10.3987/REV-96-484
Photoamination Directed toward the Synthesis of Heterocyclic Compounds

Masahide Yasuda, Toshiaki Yamashita, Ryuji Kojima, and Kensuke Shima

*Cooperative Research Center, Miyazaki University, Gakuen-Kibanadai, Miyazaki 889-21, Japan


This paper reviews the recent author’s studies on the photoamination via electron transfer which were applied to the introduction of the amino group to C-C double bonds of several kinds of the substrates involving arenes, stilbenes, and benzo[a,d]cycloalkenes. The aminated products were used as the precursors for the synthesis of the heterocyclic compounds involving benzylisoquinolines, aporphines, isopavines, dibenzo[a,d]cycloheptenimines, and oxazepines.

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25 data found. 1 - 25 listed