HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Special Issue
Yoshio Ban's Special Issues, Vol. 42, No. 2, 1996
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■ Synthesis of Philanthotoxin Analogs with Bulky Heads Including Porphyrins. Self-assembly Monitored by Circular Dichroism
Danwen Huang, Stefan Matile, Nina Berova, and Koji Nakanishi
*Department of Chemistry, Columbia University, New York, NY 10027, U.S.A.
Abstract
Philanthotoxin (PhTX) analogs with bulky bis-iminodibenzyl and porphyrin head groups have been prepared. Exciton coupled CD studies show that dependent on the hyorophobicity of the head group PhTX analogs may get amphiphilic properties forming micelles in aqueous solution.
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■ Synthesis and Stereochemistry of 2-Methyl-4H-9,12-dioxa-1,4-diazadispiro[5.2.5.2]tetradec-1-en-3-one and Its 2H-Imidazolo-2-spirocyclohexane Analogue. An Anomalous Michael Type Cyclocondensation
Yves Langlois, Leszek Konopski, and Janusz Zachara
*Laboratoire de Synthèse des Substances naturelles, Institut de Chimie Moléculaire d'Orsay, Université de Paris-Sud, Bâtiment 410, 91405 Orsay Cedex, France
Abstract
Starting from 1,4-cyclohexanedione monoethylene ketal and methyl propiolate in ammonia-saturated methanol at 100°C we obtained 2-methyl-4H-9,12-dioxa-1,4-diazadispiro[5.2.5.2]tetradec-1-en-3-one which was subsequently transformed into its O-methyl ether - a 2H-imidazolo-2-spirocyclohexane derivative. The mechanism of formation of this new heterocyclic system by anomalous Michael type cyclocondensation was proposed.
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■ Total Synthesis of (-)-Dactylynes
Lian-xun Gao and Akio Murai
*Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan
Abstract
The first total synthesis of (-)-dactylyne (1) and (-)-isodactylyne (2), which have been isolated from sea hare, is described in detail. Critical steps in the synthesis include a stereoselective construction as well as an intramolecular ring closure of 32, and the effective double elongation reactions (59 → 63 and 64, 67 → 68, and 70 →71).
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■ A New Bis(zinc(II)-cyclen) Complex as a Novel Chelator for Barbiturates and Phosphates
Haruto Fujioka, Tohru Koike, Naoka Yamada, and Eiichi Kimura
*Department of Medicinal Chemistry, School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
Abstract
A novel bis-zinc(II) receptor (bis(ZnII-cyclen)), which has two macrocyclic tetraamine ZnII complexes connected through a m-xylene bridge, has been synthesized as a potential host for barbiturates and phosphates in aqueous solution. The new zinc(II) complex, bis(ZnII-cyclen) was proven to be an excellent host for barbital and forms a stable 1 : 1 complex (Zn2L-barbital2-) in aqueous solution (KBar = [Zn2-Lbarbital2-]/[uncomplexed Zn2L][uncomplexed barbital] =105.6 M-1 at 25°C and pH 8), wherein both imido groups of the barbital are deprotonated. The bis(ZnII-cyclen) also has a strong affinity to a bidentate phosphomonoester dianion, 4-nitrophenyl phosphate (NP2-) (KNP = [Zn2L-NP2-]/ [Zn2L][NP2-] =104.0 M-1 at 25°C).
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■ A Carbon-Carbon Bond Formation by the Reaction of 4-Chloro-6-methyl-3-phenylethynyl-2H-pyran-2-one with Active Methylene Derivatives
Yutaka Azuma, Atsuko Sato, and Mieko Morone
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
The reaction of 4-chloro-6-methyl-3-phenylethynyl-2H-pyran-2-one (2) with compounds containing active methylene group, such as diethyl malonate, acetylacetone, ethyl cyanoacetate, and malononitrile, in the presence of NaH gives 4-substituted 6-methyl-3-phenylethynyl-2H-pyran-2-one (3) and / or 6-methyl-3-phenylacetyl-2H-pyran-2-one (5).
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■ Rare Earth Salts Promoted Glycosidation of Glycosyl Fluorides
Won-Sup Kim, Shigeru Hosono, Hiroaki Sasai, and Masakatsu Shibasaki
*Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan
Abstract
A glycosidation reaction of glycosyl fluorides with free alcohol acceptors has been found to be promoted effectively by using rare earth metal salts, with or without the requirement of usual Lewis acids such as ZnCl2 and Ba(ClO4)2. Moreover, a glycosidation reaction of glycosyl fluorides with trimethylsilyl ethers has been found to be promoted more effectively by using a catalytic amount of rare earth metal perchlorates.
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■ Asymmetric Syntheses of (-)-Aphanorphine and (-)-Eptazocine
Manabu Node, Hitoshi Imazato, Ryuichi Kurosaki, Yoshikazu Kawano, Takehisa Inoue, Kiyoharu Nishide, and Kaoru Fuji
*Institute for Chemistry, Kyoto University, Uji, Kyoto 611-0011, Japan
Abstract
Formal asymmetric syntheses of (-)-aphanorphine and (-)-eptazocine were done, utilizing asymmetric nitroolefination reaction of α-methyl-δ-valerolactone and a new aromatization of Diels-Alder adducts of chiral nitroolefins with the Danishefsky’s diene.
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■ New Approach to the Imidazolutidine Moiety of MK-996
Chris H. Senanayake, Laura E. Fredenburgh, Robert A. Reamer, Ji Liu, F. Edward Roberts, Guy Humphrey, Andrew S. Thompson, Robert D. Larsen, Thomas R. Verhoeven, Paul J. Reider, and Ichiro Sinkai
*Department of Process Reseach, Merck Research Laboratories, Division of Merck & Co., Inc., P. O. Box 200,0, Rahway, New Jersey 07065, USA
Abstract
A highly effective, regio-selective synthesis of imidazolutidine (1) is described starting from readily available malonamamidine hydrochloride and 2,4-pentanedione.
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■ Biotransformation of Phenyl- and Pyridylalkane Derivatives in Rat Liver 9,000xg Supernatant (S-9)
Mitsuhiro Takeshita, Masatomo Miura, Yukiko Unuma, Sakiko Iwai, Izumi Sato, Takahiko Hongo, Toshie Arai, and Kazuhiro Kosaka
*Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan
Abstract
When phenylpropanes were incubated with phenobarbital-pretreated rat liver 9,000xg supernatant (S-9), oxidative hydroxylation occurred to give phenylpropanol (racemic), (1R, 2S)- and (1R, 2R)-phenylpropanediols, (2S)-hydroxyphenylpropanone. Incubation of pyridylethane and propane with S-9 afforded α-pyridylethanol and propanol, but those were optically inactive. During the incubation of 1-phenylpropanone, an asymmetric redox reaction simultaneously occurred to give (2S)-phenylpropanol, (1R, 2S)- or (1R, 2R)-phenyl propanediols and (2R)-hydroxyphenylpropanone. Acetylpyridines were enantioselectively reduced to afford α-pyridylethanols in high optical yields (94-98%ee). The oxidation of pyridylalkane was significantly inhibited by cytochrome P-450 inhibitor (SKF-525A). but reduction of acetylpyridines was not inhibited. Thus. cytochrome P-450 was found to be responsible for the oxidation of pyridylalkane. but not for the reduction of the ketone.
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■ Synthetic Application of Chiral 4-Methoxy-2-oxazolidinone Synthons to 2-Amino Alcohols of Biological Interest
Tadao Ishizuka, Kohei Morooka, Seigo Ishibuchi, and Takehisa Kunieda*
*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan
Abstract
The versatility as chiral synthons of (4S, 5S)- and (4R, 5R)-5-allyl-4-methoxy-2-oxazolidinones, readily obtainable from 3-[(1S)-2-exo-alkoxy-1-apocamphanecarbonyl]-2-oxazolone, is demonstrated by the facile stereospecific conversions to (2R, 3S)-3-amino-2-hydroxy-3-phenylpentanoic acid, (2R, 3R, 5E, 7E)-2-amino-5,7-tetradecadien-3-ol and (2S, 3R)-dihydrosphingosine.
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■ A Facile Synthesis of β-Lactams by the Cyclization of β-Amino Acids Exploiting 3,3'-(Phenylphosphoryl)-bis(1,3-thiazolidine-2-thione)
Yoshimitsu Nagao, Toshio Kumagai, Satoshi Tamai, Hiroshi Matsunaga, Takao Abe, and Yoshinori Inoue
*Faculty of Pharmaceutical Sciences, University of Tokushima, Sho-machi, Tokushima 770-8505, Japan
Abstract
3,3’-(Phenylphosphoryl)-bis(1,3-thiazolidine-2-thione) (5), obtained from phenylphosphonic dichloride (7) and sodium salt of 1,3-thiazolidine-2-thione (6), proved to be useful for intramolecular dehydration of various β-amino acids to give the corresponding β-lactams.
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■ Conformation and Facial Selectivities of Chiral Six-membered 1,3-Diheterocycles Involving an Enone Function
Masayuki Sato, Satoshi Sunami, and Chikara Kaneko
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Ground-state as well as excited-state reactions of chiral 1,3-dioxin-4-ones and related compounds which involve an enone function in their ring are reviewed with emphasis of the facial selectivity. Sofa conformation of the ring systems and pyramidalization of the enone portions in these heterocycles so far been proposed as the origins of the facial selectivity are summarized and the discrepancies between facial selectivities verified by experimental results and the predicted selectivities from either the conformation or the pyramidalization are pointed out. The reactions of chiral 1,3-dioxane-4,6-diones, 1,3-oxazine-4,6-diones and their 5-benzylidene derivatives are also surveyed. Finally, the present authors’ opinion which accounts for all of the reported reactions having facial selectivities is proposed. This review also includes the present authors’ opinion for the origin of these conformation and pyramidalization.
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■ Synthesis of Fluorine Analogs of Natural Porphyrins Potentially Useful for Diagnosis and Therapy of Cancer
Akira Ando and Itsumaro Kumadaki
*Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata-shi, Osaka 573-0101, Japan
Abstract
Hematoporphyrin derivative (HpD) or Photofrin II are used for photosensitizer of photodynamic therapy (PDT) of cancer. However, these are complex mixtures of porphyrin derivatives. We have synthesized fluorine analogs of naturally important porphyrin derivatives, such as protoporphyrin and hematoporphyrin, which would be useful for diagnosis and therapy of cancer. In this review, we wish to show our syntheses of these fluorine analogs and the localization of these porphyrins to tumor cells and some tissues.
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■ Chemical Identification of Binding Sites for Calcium Channel Antagonists
Hitoshi Nakayama and Yuichi Kanaoka
*Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-hon-machi, Kumamoto 862-0973, Japan
Abstract
Binding sites of three typical calcium channel antagonists including heterocyclic 1,4-dihydropyridine and benzothiazepines, and phenylalkylamines, have been identified within the primary structures of calcium channels by photoaffinity labeling technique. We briefly review the results and discuss the future prospect.
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■ Variations in the Chemical Shift of Benzylic Methylene Carbon of Prenyl Group on Heterocyclic Prenylphenols
Toshio Fukai and Taro Nomura
*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Abstract
13C Nmr examination of 377 kinds of heterocyclic prenyl(geranyl)phenoIs has shown that the chemical shift of the benzylic methylene signal of prenyl (geranyl) group (C1) was depended upon the substituents located at the adjacent positions. The prenyl (geranyl) groups could be classified into the six types and the chemical shifts of the C1 signal were observed in the restricted range specific to each type. The classification of the chemical shift of the C1 signal is useful for the structure determination of complex heterocyclic prenyl(geranyl)phenol. The chemical shifts of the C1 signals of these 377 heterocyclic prenyl(geranyl)phenoIs are listed up.
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■ Sphingosine-related Marine Alkaloids: Cyclic Amino Alcohols
Jun'ichi Kobayashi and Masami Ishibashi
*Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan
Abstract
Two classes of aliphatic alkaloids, pseudodistomins and penaresidins, were isolated from an Okinawan marine tunicate Pseudodistoma kanoko and a sponge Penares sp., respectively. They have piperidine and azetidine skeletons, respectively; these cyclic amino alcohols are likely to be biogenetically related to sphingosine derivatives. Other sphingosine-related metabolites from marine microorganisms are also described.