HETEROCYCLES

■ Contents

■ Preface
Honoring the 70^th Birthday of Professor Yoshito Kishi

Robert M. Williams

*University Distinguished Professor, Colorado State University, Department of Chemistry, Fort Collins, Colorado 80523, U.S.A.

■ Biographical Sketch

Yoshito Kishi*

*Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge
Massachusetts 02138, U.S.A.

■ Research Summary of Kishi Group

Yoshito Kishi*

*Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge
Massachusetts 02138, U.S.A.

■ Publications: Yoshito Kishi

Yoshito Kishi*

*Department of Chemistry, Harvard University, 12 Oxford Street, Cambridge
Massachusetts 02138, U.S.A.

■ Bioactive Compounds from Mushrooms

Hirokazu Kawagishi* and Cun Zhuang

*Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, 836 Ohya, Shizuoka 422-8529, Japan

Abstract

Anti-dementia compounds, anti-MRSA compounds, osteoclast-forming suppressing compounds, gastrointestinal toxins and sick-from-drinking toxins from mushrroms are explicated.

■ Heteroditopic Receptors

Nadezhda A. Itsikson, Irina V. Geide, Yuri Yu. Morzherin, Anatoly I. Matern, and Oleg N. Chupakhin*

*Department of Heterocyclic Chemistry, I. Postovsky Institute of Organic Synthesis of RAS, 20/20, S. Kovalevskaya/Akademicheskaya st., 620219, Ekaterinburg, Russia

Abstract

The review outlines the recent advances in the field of coordination chemistry, and is focusing on the function-oriented design of heterotopic co-receptors. Comparative analysis of receptor ability for various classes of organic compounds toward two different substrates, ion pairs or zwitterionic species is presented.

■ Stereoselective Synthesis of N¹-6-Methyluridine and Related 2-Substituted Analogues

Marco Radi, Elena Petricci, Federico Corelli, and Maurizio Botta*

*Dipartimento Farmaco Chimico Tecnologico, Università di Siena, Via Aldo Moro, 53100 Siena, Italy

Abstract

Coupling reaction of 2-substituted-6-methyl-4(3H)-pyrimidinones (1a,b) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (ABR) afforded the corresponding N¹-2,6-disubstituted nucleosides (2a,b) without any trace of the N³-isomer. The 2-methylthio-6-methyl derivative (2b) has then proved to be a key intermediate for the synthesis of N¹-6-methyluridine (4) and the corresponding N¹-2-amino-6-metyhl derivative (5), suggesting the possibility to obtain different 2,6-disubstituted derivatives by means of methylthio nucleophilic substitution. A successful solid phase application was also shown.

■ Synthesis and Properties of Acene Dimers Linked by a 1,3,4-Oxadiazole Spacer

Katsuhiko Ono,* Mayuko Wakida, Ryohei Hosokawa, Katsuhiro Saito, Jun-ichi Nishida, and Yoshiro Yamashita

*Department of Life and Material Engineering, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan

Abstract

Acene dimers linked by a 1,3,4-oxadiazole spacer were synthesized and their physical, optical, and electrochemical properties were investigated. The melting points and electron affinities of the dimers increased in the following order: benzene, naphthalene, and anthracene. The longest absorption maximum was red-shifted with an increase in the number of benzene rings. The π-conjugation between the two acene moieties through the oxadiazole spacer was not strong. Although no OFET properties were observed in a bottom contact device using the anthracene dimer as an active layer, the molecules were perpendicularly arranged on the substrate to form π-stacking films as observed in the X-Ray diffraction analysis.

■ A New Method for Efficient Coupling of Indole and Epoxide Catalyzed with Yb(OTf)₃, and Application to the Total Synthesis of Kurasoin B

Satoshi Tsuchiya, Toshiaki Sunazuka, Tatsuya Shirahata, Tomoyasu Hirose, Eisuke Kaji, and Satoshi Omura*

*Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan

Abstract

The Yb(OTf)₃ catalyzed reaction between indole and epoxide in simple and mild condition was developed. This method is suitable for gram-scale synthesis of 3-indolelactic acid derivatives. The asymmetric synthesis of kurasoin B was achieved using chiral 3-indolelactic acid methyl ester as the starting material.

■ Total Synthesis of (-)- and ent-(+)-4-Desacetoxy-5-desethylvindoline

Hayato Ishikawa and Dale L. Boger*

*Department of Chemistry and, The Skaggs Institute for Chemcial Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, U.S.A.

Abstract

A concise synthesis of (-)- and ent-(+)-4-desacetoxy-5-desethylvindoline (2), a key analogue of vindoline, is disclosed enlisting an intramolecular tandem [4+2]/[3+2] cycloaddition cascade of 1,3,4-oxadiazole (5) to assemble the pentacyclic skeleton of 2 in a single step that forms three new rings, four C-C bonds, and sets all five key stereocenters. The subsequent efforts on the elaboration of 6 to 2 revealed two subtle features key to our recent total syntheses of vindoline, vindorosine, and related natural products based on this strategy.

■ Stereoselective Mannich-Like Reactions of Ester Enolates Generated on Sugar Templates: A Novel Access to a Key Intermediate for 1β-Methylcarbapenem Synthesis

Daisuke Sasaki, Daisuke Sawamoto, Ken-ichi Takao, Kin-ichi Tadano,* Masayuki Okue, and Keiichi Ajito

*Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku Yokohama 223-8522, Japan

Abstract

The Mannich-like reactions of the enolates generated from 2,3-di-O-protected 6-deoxy-4-O-propionyl-α-D-glucopyranosides with (3R,4R)-4-acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]azetidin-2-one were investigated. The corresponding 2,3-di-O-methyl derivative provided the Mannich adduct in good to excellent stereoselectivity. From the major adduct, the azetidin-2-one incorporating an α-methyl acetic acid side chain at the C-4 position with β-configuration was obtained by alkaline hydrolysis. This product, (3S,4S)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-[(R)-1-carboxyethyl]azetidin-2-one, is a useful intermediate for the 1β-methylcarbapenem synthesis.

■ An Example of Overriding Cyanation during Reaction of a Primary Alcohol with o-Nitrophenyl Selenocyanate

Shuzhi Dong and Leo A. Paquette*

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

Abstract

The first example of a nitrile as the end product of a Mitsunobu substitution involving o-nitrophenyl selenocyanate and tributylphosphine is reported. Neighboring group participation operates and leads favorably to competitive formation of a 2-cyanotetrahydrofuran.

■ Synthesis of Oxa-Bridged 7- and 8-Membered Rings via Indium-Mediated Annulation of 1,4- and 1,5-Dicarbonyl Compounds with 3-Iodo-2-[(trimethylsilyl)methyl]propene

Amir Allatabakhsh, Minh Pham, and Thomas Minehan*

*Department of Chemistry and Biochemistry, California State University, Northridge, 18111 Nordhoff St., Northridge, CA 91330, U.S.A.

Abstract

A variety of 1,4- and 1,5-dicarbonyl compounds undergo reaction with 3-iodo-2-[(trimethylsilyl)methyl]propene in the presence of indium metal in aqueous media to produce oxa-bridged 7- and 8-membered rings in good yields. The reaction mechanism likely involves intermolecular indium allylation of one carbonyl of the substrate, followed by indium-halide promoted intramolecular allylsilane cyclization. This procedure offers an environmentally friendly alternative to the analogous tin-mediated annulation process.

■ Crystal Structures of Coumarin-3-carbamate Derivatives with Herbicidal Activities

Hajime Takahashi, Haruko Takechi, Kanji Kubo,* and Taisuke Matsumoto

*School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

Coumarin-3-carbamate derivatives were prepared by the reaction of alcohols with coumarin-3-carbonyl azide. The testosterone derivative has herbicidal activities, but the benzene derivative does not have the activities. The crystal structures of two coumarin-3-carbamate derivatives were analyzed by X-ray crystallography. The crystals of the testosterone derivative had intermolecular N–H···O, C–H···O, and C–H···π interactions.

■ Diastereoselective Reduction of α-Imino Esters with Tris(trimethylsilyl)aluminum

Makoto Shimizu,* Yasuki Niwa, Takeshi Nagai, and Iwao Hachiya

*Department of Chemistry for Materials, Graduate School of Engineering, Mie University, 1577 Tsu, Mie 514-8507, Japan

Abstract

Tris(trimethylsilyl)aluminum was found to be a good chemoselective reducing reagent for α-imino esters to give α-amino esters in good yields. Application to the reduction of 3,5-disubstituted 5,6-dihyro-2H-1,4-oxazine-2-ones realized a stereoselective conversion into cis-3,5-disubstituted morpholine-2-ones.

■ New Preparation of Tridentate Bis-oxazoline Carbazole Ligand Effective for Enantioselective Nozaki-Hiyama Reaction

Masahiro Inoue and Masahisa Nakada*

*Department of Chemistry, School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan

Abstract

A new preparation of the tridentate bis-oxazoline carbazole ligand 1 is described. This method features direct formation of the amide, which is a precursor of the ligand 1, via the Pd-catalyzed amidation and following BF₃·OEt₂ mediated oxazoline formation. This method required only 2 steps from the aryl iodide to form the bis-oxazoline ligand; hence, it would be generally used for preparing other bis-oxazoline ligands.

■ Stereoselective Synthesis of the AB-Ring Fragment of Gambieric Acid A

Haruhiko Fuwa,* Akihiro Suzuki, Kazushi Sato, and Makoto Sasaki*

*Laboratory of Biostructural Chemistry, Graduate School of Life Sciences, Tohoku University, 1-1 Tsutsumidori-amamiya, Aoba-ku, Sendai 981-8555, Japan

Abstract

Stereoselective synthesis of the AB-ring fragment of gambieric acid A has been accomplished, wherein (i) an acetylide-aldehyde coupling for fragment assembly and (ii) construction of the tetrahydrofuran A-ring via a diastereoselective bromoetherification were successfully employed as key transformations.

■ Synthesis and Biological Activities on Batzelladine Derivatives

Jun Shimokawa, Yumi Iijima, Yuichi Hashimoto, Harumi Chiba, Haruo Tanaka, and Kazuo Nagasawa*

*Division of Biotechnology and Life Science, Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588, Japan

Abstract

Structure-activity relationship studies on batzelladines A and D were examined. Seven batzelladine derivatives, including 24-epi-batzelladine A (3) and 7-epi-batzelladine D (4), were synthesized. The inhibitory activity of these derivatives on binding of gp120 with CD4 was evaluated by the use of ELISA-based assay method. For the potent biological activities of batzelladines, tricyclic guanidine moiety, a common structure of batzelladine A and D, and side chain bearing guanidine functional group were found to be mandatory.

■ Synthesis of Cyclic Ether via an Intramolecular Barbier Reaction of Iodo Ester with Butyllithium

Tatsuo Saito, Toshiharu Takeuchi, Miyuki Matsuhashi, and Tadashi Nakata*

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

Abstract

Intramolecular Barbier reaction of 2-(2-iodoethyl)-3-tetrahydropyranyl esters or acyclic 4-iodobutyl ester with t-BuLi or n-BuLi effected cyclization to give six-membered hemiacetals. Based on the present reaction, the synthesis of 2,6-syn-tetrahydropyran and trans-fused polycyclic ethers, and coupling of the AB- and E’FG-rings of gambierol were accomplished.

■ The Regiochemistry of the o-Claisen Rearrangement of Bis-(alloxy)polycyclic Aromatics

George Majetich,* Jianhua Yu, Yang Li, and Scott H. Allen

*Department of Chemsitry, The University of Georgia, Athens, Georgia 30602, U.S.A.

Abstract

The o-Claisen rearrangement of bis-(allyloxy) naphthalenes, anthracenes and phenanthrenes is regiospecific and is consistent with resonance theory and molecular orbital calculations.

■ Versatile Synthesis of 2,2-Disubstituted Indolinones via Protected Indolones Generated by One-Pot Multi-oxidation of 2-Substituted Indoles

Matthew J. Buller, Travis G. Cook, and Yoshihisa Kobayashi*

*Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0343, U.S.A.

Abstract

The discovery of expeditious multi-oxidation of indoles to masked indolones led us to the development of a versatile synthetic method to access a variety of 2,2-disubstituted indolinones bearing two different substituents.

■ Studies toward the Total Synthesis of Grandisine A: Synthesis of 9-epi-Grandisine A

David J. Maloney and Samuel J. Danishefsky*

*Laboratory for Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, U.S.A.

Abstract

A concise synthesis of 9-epi-grandisine A is described, which makes use of a Lewis acid-promoted hetero-Diels-Alder reaction to construct the tricyclic skeleton. Attempts to obtain grandisine A through a late-stage controlled epimerization are also discussed.

■ Diastereoselective Construction of Indolo[2,3-a]quinolizidine Skeleton by Cycloaddition Reaction of 3,4-Dihydro-β-carbolines with γ,δ-Unsaturated β-Ketoesters

Kazuhiro Nagata, Yusuke Sekishiro, and Takashi Itoh*

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

Abstract

Cycloaddition reaction of 3,4-dihydro-β-carboline derivatives with γ,δ-unsaturated-β-ketoesters afforded octahydroindolo[2,3-a]quinolizidines in one step. The reaction was applied to the synthesis of a potential precursor of Eburnamine-Vincamine alkaloids in a highly diastereoselective manner.

■ Total Synthesis of Citrafungin A

Mumen F. A. Amer, Keisuke Takahashi, Jun Ishihara, and Susumi Hatakeyama*

*Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

Citrafungin A, a member of the alkyl citrate class of natural products, was synthesized for the first time employing a convergent approach involving aldol reaction of (R)-4-((1E,5Z)-tetradeca-1,5-dienyl)-γ-butyrolactone with tert-butyl 4-(p-methoxybenzyloxy)-2-oxobutanoate and installation of (2R,3S)-tri-tert-butyl isocitrate.

■ Hilbert-Johnson Reaction under High Pressure: A Facile Preparation of 2-Pyridones

Kiyoshi Matsumoto,* Yukio Ikemi, Machiko Suda, Hirokazu Iida, and Hiroshi Hamana

*Faculty of Pharmaceutical Sciences, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan

Abstract

For the first time, a facile synthesis of 2-pyridones utilizing a classical Hilbert-Johnson reaction of 2-methoxypyridines with haloalkanes under high pressure has been achieved. The reactions were sensitive to steric hindrance of haloalkanes.

■ A Novel Indole Synthesis via Conjugate Addition of Pyrrolidine to o-Nitrophenylacetylenes

Hidetoshi Tokuyama, Takaki Makido, Yuki Han-ya, and Tohru Fukuyama*

*Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Abstract

A novel indole synthesis reaction by conjugate addition of pyrrolidine to o-nitrophenylacetylenes and subsequent reductive cyclization of o-nitroarylenamines was developed.

■ Studies on Enol Carbonate Chemistry: Stereoselective Construction of Vicinal Quaternary Benzylic Centers in the Bis-oxindole Series

Candice Menozzi, Peter I. Dalko,* and Janine Cossy

*Laboratory of Organic Chemistry, University Paris 5, CNRS, 10 rue Vauquelin, 75231 Paris Cedex 05, France

Abstract

The Steglich-type intramolecular acyl transfer of bis-oxindole enol carbonate derivatives 9a-c affords selectively the monorearranged products 11a-c. In turn, Pd(0)-mediated allyl transfer of the bis-Alloc derivative 9c allows an efficient double C-allylation leading preferentially to the d/l isomer.

■ Synthesis of the JK Ring Fragments of Yessotoxin and 42,43,44,45,46,47,55-Heptanor-41-oxoyessotoxin

Koji Watanabe, Hiroaki Minato, Michio Murata, and Tohru Oishi*

*Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-8531, Japan

Abstract

The JK ring fragment (7) of 42,43,44,45,46,47,55-heptanor-41-oxoyessotoxin was synthesized via enyne metathesis and 6-exo cyclization of a hydroxy epoxide. Conversion of 7 into the JK ring fragment (6) of yessotoxin was achieved in a single step by treatment with an alkenyllithium.

■ Studies of Zoanthamine Alkaloids. A General Scheme for the Preparation of Functionalized 8-Oxa-6-azabicyclo[3.2.1]octanes

David R. Williams, Samarjit Patnaik, and Guillermo S. Cortez

*Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, IN 47405-7102, U.S.A.

Abstract

Studies have provided an efficient preparation of 8-oxa-6-azabicyclo[3.2.1]octanes. These functionalized hemi-aminal systems are readily incorporated into a variety of structures which exhibit the pharmacophore characteristics found in the zoanthamine alkaloids.