HETEROCYCLES

■ Contents

■ Preface

Markus Kalesse

*Institute of Organic Chemistry, University of Hannover, Schneiderberg 1B, D-30167 Hannover, Germany

■ Preface

Hans-Joachim Knölker

*Institute of Organic Chemistry, Technical University Dresden, Bergstrasse 66, D-01069 Dresden, Germany

■ Preface

Ichiya Ninomiya

*1-7-17 Hanayashiki, Kawanishi-shi 666-0035, Japan

■ Curriculum Vitae

Ekkehard Winterfeldt

*Institute of Organic Chemistry, University of Hannover, Schneiderberg 1B, D-30167 Hannover, Germany

■ Summary

Ekkehard Winterfeldt

*Institute of Organic Chemistry, University of Hannover, Schneiderberg 1B, D-30167 Hannover, Germany

■ Publications

Ekkehard Winterfeldt

*Institute of Organic Chemistry, University of Hannover, Schneiderberg 1B, D-30167 Hannover, Germany

■ Structure and Biological Activity of the Furan-Diterpenoids from the Genera Leonotis and Leonurus

Franco Piozzi,* Maurizio Bruno, Sergio Rosselli, and Antonella Maggio

*Department of Organic Chemistry, University of Palermo, Viale delle Scienze, 90128 Palermo, Italy

Abstract

The present review, covering the literature up to 2006, reports the chemistry and the biological activities of the diterpenoids occurring in the aerial parts of species belonging to the genera Leonotis and Leonurus, family Lamiaceae.

■ Bioactive Nitrogenous Metabolites from Ascidians

Weifang Wang and Michio Namikoshi*

*Department of Natural Product Chemistry, Tohoku College of Pharmacy, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan

Abstract

Ascidians (class Ascidiacea) belong to the subphylum Urochordata (Tunicata) and are generally called as tunicates because the body is covered by tunic, a sack-like case, or sea squirts since they spurt water when disturbed. Nitrogenous secondary metabolites form more than 80% of new natural products obtained from ascidians and showed a wide variety of bioactivities. This review describes the structures and bioactivities of major classes of unique nitrogenous ascidian metabolites: cyclic peptides, in which aplidine is in the Phase II clinical trials, pyridoacridine alkaloids, β-carboline alkaloids, lamellarins and related pyrrole alkaloids, ecteinascidins (ETs, ET 743 completed the Phase III clinical trials), diterpene and steroidal alkaloids, and polysulfur alkaloids.

■ Aryne-Mediated Synthesis of Heterocycles

Diego Peña, Dolores Pérez, and Enrique Guitián*

*Department of Organic Chemistry, University of Santiago, 15706 Santiago de Compostela, Spain

Abstract

Arynes have been used as intermediates in the synthesis of heterocycles with a variety of heteroatoms (O, N, S, Ni, Pd) and rings sizes (from 5 to 8-membered).

■ Methodology for the Synthesis of Pyridines and Pyridones: Development and Applications

Marco A. Ciufolini* and Bryan K. Chan

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

Abstract

We review some reactions devised in our laboratory for the rapid assembly of pyridines and pyridones. Applications of the new methods in the total synthesis of lavendamycin, pyridoacridine and phenanthroizidine alkaloids (pyridine chemistry), and of camptothecin, nothapodytine B and streptonigrone (pyridone-forming reactions) are described.

■ Survey of Chemical Syntheses of the Pyrrolizidine Alkaloids Turneforcidine and Platynecine

John A. Vanecko and Frederick G. West*

*Gunning/Lemieux Chemistry Center, Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada

Abstract

The necine bases turneforcidine and platynecine have inspired a great deal of synthetic effort. Key challenges include the construction of the bicyclic pyrrolizidine ring system and controlled introduction of three contiguous stereocenters. This review will survey the many diverse strategies by which these natural products have been synthesized.

■ Effective Synthetic Routes to 4H- and 10bH-Pyrido[2,1-a]isoindol-6-ones

Robert D. Dura, Isabelle Modolo, and Leo A. Paquette*

*Department of Chemistry, The Ohio State University, 100 West 18th Avenue Columbus, Ohio 43210, U.S.A.

Abstract

Two previously unknown pyridoisoindolones have been synthesized from N-allylphthalimide as the common precursor. The methodologies allowing these constructions include a novel twofold dehydrobromination involving an N-acyliminium ion that experiences regiocontrolled hydration. The synthetic routes are completed by indirect introduction of the diene unit.

■ Photoinduced Electron Transfer-Initiated Enantioselective Cyclization of N-Benzoyl-α-dehydroarylalanine tert-Butyl Esters in the Presence of Chiral Amine

Haruo Watanabe, Kei Maekawa, Tetsutaro Igarashi, and Tadamitsu Sakurai*

*Material and Life Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

The asymmetric photocyclization of the title compounds in 1,2-dichloroethane was found to proceed cleanly in the presence of primary, secondary, or tertiary chiral amine to give the corresponding cis- and trans-3,4-dihydrooxazole derivatives in enantiomeric excess (ee) of 11-38% and 6-33%, respectively, depending on the steric factor of the aryl substituent as well as on the hydrogen-bonding ability of the chiral amine.

■ Synthesis of a Series of Structural Analogues of the Cinchona Alkaloids

Kadzushi Furukawa, Masahiro Katsukawa, Mohammad Nuruzzaman, and Yuichi Kobayashi*

*Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan

Abstract

Five olefins, each possessing an aryl (Ar) group, an aliphatic moiety, and a protected amino group as N-Teoc (-CO₂(CH₂)₂TMS) or N₃ at the aliphatic end, were converted to the corresponding epoxides with high ee. The amino group was generated by deprotection of the N-Teoc group with CsF or by Staudinger reaction of the azide group at elevated temperatures, under which the intramolecular epoxide ring-opening with the resulting amino group took place concomitantly to afford the analogues of the Cinchona alkaloids.

■ Synthesis and Properties of PET Fluoroionophore Having 1-Pyridin-2-ylpiperazine Group

Kanji Kubo,* Tadamitsu Sakurai, Hajime Takahashi, and Haruko Takechi

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

Abstract

9-[4-(2-pyridinyl)-1-piperazinyl]methyl]anthracene (1) and 9,10-bis[[4-(2-pyridinyl)-1-piperazinyl]methyl]anthracene (2) were synthesized as a fluorescent PET sensor. The sensor functions as an off-on-off fluorescence switch for proton.

■ Substrate-Controlled Formal Synthesis of (+)-Laurenyne by a Chemoselective Chelation-Controlled Alkylation Strategy

Byungsook Kim, Gukwha Cheon, Janghyun Park, Hyunjoo Lee, Hyoungsu Kim, Sanghee Kim, and Deukjoon Kim*

*The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shillim-Dong, San 56-1, Kwanak-Gu, Seoul 151-742, Korea

Abstract

A substrate-controlled formal synthesis of (+)-laurenyne has been accomplished featuring a highly stereoselective chemoselective chelation-controlled amide enolate alkylation for synthesis of the α,α’-syn-bis-alkene without resorting to use of a chiral auxiliary.

■ Titanium Tetraiodide Promoted Reductive Opening of 2-(1-Benzyloxyiminoethyl)aziridines, Leading to Aza-Aldol Reaction

Makoto Shimizu,* Shuji Nishiura, and Iwao Hachiya

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

Abstract

Reductive ring-opening of 2-(1-benzyloxyiminoethyl)aziridines was regioselectively carried out with titanium tetraiodide to form the titanium aza-enolates, which in turn were subjected to addition reaction with aldehydes to give aza-aldol products in good yields with high diastereoselectivities.

■ Synthesis of (±)-Lauthisan

Naoki Miyakoshi, Yuki Ohgaki, Kosuke Masui, and Chisato Mukai*

*Division of Pharmaceutical Sciecnes, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Abstract

A new total synthesis of (±)-lauthisan was accomplished based on the endo-mode ring-closing reaction of 1-(5-hydroxyhept-1-yl)-3-pentyl-1-phenylsulfonylallene.

■ An Alternative Regioselective Ring-Opening of Epoxides to Chlorohydrins Mediated by Chlorotitanium(IV) Reagents

Kiyoshi Nishitani,* Kyoko Shinyama, and Koji Yamakawa

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

Abstract

A regioselective cleavage of various epoxides to vic-chlorohydrin isomers by using TiCl₄ or TiCl₄-Ti(O-i-Pr)₄ complex was investigated. The less substituted alcohols, C2-attack products, were formed by the use of TiCl4 in CH₂Cl₂. On the other hand, the less substituted chlorides, C1-attack products, were formed by using TiCl(O-i-Pr)₃ in DMF. These regioselectivities depend on both the acidity of the Lewis acids and the polarity of the solvents.

■ Synthesis of (-)-Trolline, (-)-Crispine A and (-)-Crispine E

Takuya Kanemitsu, Yuki Yamashita, Kazuhiro Nagata, and Takashi Itoh*

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

Abstract

Biologically active 1-subsutituted tetrahydroisoquinoline alkaloids, (-)-trolline, (-)-crispine A, and (-)-crispine E were synthesized using a chiral isoquinolinecarbaldehyde as a key material. The aldehyde was readily obtained from a 1-cyanoisoquinoline, and subjected to a Horner-Wadsworth-Emmons reaction. The chiral tetrahydroisoquinoline derivative thus obtained was used for the synthesis of the optically active isoquinoline alkaloids.

■ Spirocyclization of an N-Acyliminium Ion with Substituted Pyridine: Synthesis of Tricyclic Spirolactams Possessing Pyridine or Pyridone Nucleus

Hideki Abe, Kei-ichi Takaya, Kazuhiro Watanabe, Sakae Aoyagi,* Chihiro Kibayashi, and Tadashi Katoh*

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

Abstract

Spirocyclization of an N-acyliminium ion with pyridine activated by a 2-methoxy substituent as an aromatic π-nucleophile was developed. The reactions proceeded in the presence of Brønsted acids at a high temperature, producing tricyclic spirolactams that possess the ability to act as conformationally constrained nicotine analogues.

■ A Practical Route to Pyrazines and Quinoxalines, and an Unusual Synthesis of Benzimidazoles

Catherine Mougin, Julien Sançon, and Samir Z. Zard*

*Department of Chemistry, Ecole Polytechnique, CNRS UMR 7652, F-91128 Palaiseau, France

Abstract

1,2-Dicarbonyl compounds can be accessed by a radical addition-transfer of xanthates and used for the synthesis of pyrazines and quinoxalines, as well as in an unusual approach to benzimidazoles.

■ Formation of Hetero-Boroxines: Dynamic Combinatorial Libraries Generated through Trimerization of Pairs of Arylboronic Acids

Yuji Tokunaga,* Hiroki Ueno, and Youji Shimomura

*Department of Materials Science and Engineering, Faculty of Engineering, Fukui University, Bunkyo, Fukui 910-8507, Japan

Abstract

Condensation of pairs of arylboronic acids provided homo- and hetero-boroxines in solution as evidenced from NMR spectra, and those boroxines were detected in the gas phase by GC-MS spectrometry. Equilibrium constants for the formation of these boroxines in solution were obtained through integration of pertinent signals in the NMR spectra of the mixtures of boronic acids.

■ Conformational Biasing in 1,3-Oxidative Rearrangements of Dienols

George Majetich,* Hisaya Nishide, Ryan M. Phillips, and Jianhua Yu

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

Abstract

1-Vinyl-2-cycloalkenols are oxidized to form conjugated dienones in useful yields. Although this oxidative rearrangement is general, severe steric interactions can favor the formation of a conjugated dienal instead of a conjugated dienone. Several heterocyclic analogues were also studied.

■ Suzuki-Miyaura Coupling of Benzylic Carbonates with Heteroarylboronic Acids

Ryoichi Kuwano* and Jung-Yi Yu

*Department of Chemistry, Faculty of Science, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan

Abstract

Cross-coupling of benzylic carbonates with heteroarylboronic acids successfully proceeded in the presence of the palladium catalyst that was generated in situ from [Pd(η³-C₃H₅)Cl]₂ and a chelate bisphosphine DPPPent. Various heteroarylboronic acids were applicable to the catalytic cross-coupling, giving the desired benzylated heteroaromatics in high yields.

■ Synthesis and Structure of One-Dimensional Linear Copper(II) Coordination Polymer Bridged by Dicyclopentanopyrazine

Keiji Nakano, Kengo Miyata, and Masato Kitamura*

*Research Center for Materials Sciences and Department of Chemistry, Graduate School of Science, Nagoya University, Chikusa, Nagoya, Aichi 464-8602, Japan

Abstract

Crystalline Copper(II) coordination polymers bridged by dicyclopentanopyrazine (1), CuCl₂-1, were synthesized. The coordination geometries of the metal centers were tuned to square planar, orthogonal to the plane of the pyrazine ring, by steric hindrance from the methylene chains of pyrazine derivatives.

■ Synthesis of Psymberic Acid

Birgit Henßen, Elena Kasparyan, Gernot Marten, and Jörg Pietruszka*

*Institute of Bioorganic Chemistry, Heinrich-Heine-University Duesseldorf/FZ Juelich, Stetternicher Forst, Geb. 15.8, D-52426 Juelich, Germany

Abstract

A short synthesis of the unique side-chain of psymberin (1) — the psymberic acid (4) — is presented. Notable features of it include a highly selective aldol addition and an attempted enzymatic resolution step.

■ Synthesis and Properties of Bis(1,3-benzodithiole)-Type Redox Systems Containing a Xylyl Rotator Unit: A New Type of Redox-Responsive Molecular Rotor

Yuzuru Uchiyama, Akira Ohta,* and Kunihide Fujimori

*Department of Chemistry, Faculty of Science, Shinshu University, Asahi, Matsumoto 390-8621, Japan

Abstract

A new type of redox-responsive molecular rotors (3²⁺/4) possessing a xylyl rotator unit have been designed and synthesized. Reduction of 3²⁺ with zinc gave the corresponding cyclization products (4), from which dications (3²⁺) were regenerated upon oxidation. Cyclic voltammetry also showed the interconversion between 3²⁺ and 4. Variable-temperature ¹H NMR measurements revealed that the rotational barriers of the xylyl units in the neutral states (4) are higher than those in the dication states (3²⁺).

■ Stereoselective Synthesis of the GHI-Ring of Maitotoxin, a Marine Polycyclic Ether

Masanori Satoh, Masaki Mori, and Tadashi Nakata*

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

Abstract

The GHI-ring of maitotoxin, a marine polycyclic ether, was stereoselectively synthesized by way of SmI2-induced reductive cyclization of β-alkoxyacrylate and aldehyde.