HETEROCYCLES

■ Contents

■ A Novel Heterocumulenic Pauson-Khand Reaction of Alkynylcarbodiimides: A Facile and Efficient Synthesis of Heterocyclic Ring-fused Pyrrolinones

Takao Saito,* Masahiro Shiotani, Takashi Otani, and Satoshi Hasaba

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

Abstract

The first examples of the heterocumulenic Pauson-Khand reaction are described. Alkynylcarbodiimides undergo an intramolecular Pauson-Khand cycloaddition upon heating in the presence of Mo(CO)₆ and DMSO to afford 4,5-dihydro-1H-pyrrolo[2,3-b]pyrrolin-2-ones and 1H-pyrrolo[2,3-b]indol-2-ones.

■ Indoloquinones, Part 8. Palladium(II)-catalyzed Total Synthesis of Murrayaquinone A, Koeniginequinone A, and Koeniginequinone B

Hans-Joachim Knölker and Kethiri R. Reddy

*Institut für Organische Chemie, Technische Universität Dresden, Bergstrasse 66, 01069 Dresden, Germany

Abstract

Regioselective addition of the appropriate arylamines to 2-methyl-1,4-benzoquinone followed by a palladium(II)-catalyzed oxidative cyclization opens up an efficient route to the naturally occurring 3-methylcarbazole-1,4-quinone alkaloids murrayaquinone A, koeniginequinone A, and koeniginequinone B.

■ Synthesis and Crystal Structure of New Dinitro Derivatives of Sesquiterpene Lactone Achillin

Adekenov Sergazy Mynzhasarovich,* Rakhimova Bibigul Bagdatovna, Kulyjasov Arman Tabylovich, Seema Zareen, M. Iqbal Choudhary, and Atta-ur-Rahman

*International Centre for Chemical Sciences, H. E. J. Research Institute of Chemistry, University of Karachi, Karachi-75270, Pakistan

Abstract

An unexpected dinitro derivative (2) of sesquiterpene lactone achillin (1), isolated from the aerial part of Achillea micrantha Wild., was formed when this compound was exposed to gaseous NOCl in CHCl₃. This derivative was transformed into dinitrocarbonic acid (3) in pyridine in 30 minutes and in quantitative yield. The structures of these compounds were unambiguously determined by single-crystal X-Ray diffraction analysis.

■ High Yield Synthesis, Separation and Structural Characterization of New [n+n]-Polyazamacrocycles

Markus Allmendinger, Philipp Zell, Amal Amin, Ulf Thewalt, Martti Klinga, and Bernhard Rieger*

*Department of Materials and Catalysis, University of Ulm, Albert-Einstein-Allee 11, 89069 ULM, Germany

Abstract

t-Bu- and isopropyl-substituted aromatic dialdehydes (1a-c) and diamines (2a-f) were used to synthesize a series of imine macrocycles (3a-m). The highly selective cyclization reaction resulted either in a [2+2] stoechiometry or in a mixture of different [n+n] cycles, depending on the diamine building block. For some defined macrocycles (3b, 3d, 3e) the structure was elucidated by single crystal X-Ray diffraction that revealed a column-like arrangement of the macrocycles in the solid state. Mixtures of macrocycles were investigated with a combination of MALDI-Tof and analytical GPC which brought significant improvements in the determination of the exact size distribution. Isolated higher homologues of polyimine cycles were made available by preparative GPC for the first time. The possibility to reduce the imine macrocycles quantitatively to their corresponding amine analogues was demonstrated exemplary by the reduction of two pyridine containing cycles (4a-b).

■ A New Addition-Rearrangement of [1,4]Thiazine-2-thiones with Aryl-1,2,4-triazoline-3,5-diones

Nuria García, Pedro Fuertes, Susana Barriga, Ana G. Neo, Daniel Miguel, and Tomás Torroba*

*Department of Chemistry, Faculty of Sciences, University of Burgos, 09001 Burgos, Spain

Abstract

Arylcarbamoylimino derivatives of the (1,3-dithiol-2-ylidene)[1,2]dithiolo[3,4-b][1,4]thiazine ring system were synthesized by a new addition-rearrangement reaction of [1,2]dithiolo[1,4]thiazine-2-thiones with 4-aryl-1,2,4-triazoline-3,5-diones.

■ A Novel Substitution Reaction of Tetrahydropyrano[3,4-b]indole Derivative — Chain Extension and Structural Correlation Study

Shan-Yen Chou

*Development Center for Biotechnology, Hsi-Chih Research Park 101, Lane 169, Kang Ning St, Hsi Chih Cheng, Taipei Hsien, Taiwan, R.O.C.

Abstract

An unusual cyanation with rearrangement of a 1-chloromethyl- tetrahydropyrano[3,4-b]indole-1-acetic acid ester derivative is reported. The resulting C-1 chain extension product is identified by correlation studies and spectral method.

■ Nucleophilic Reactions at Optically Active Bis(4-methyl-5-phenyl-1,3-oxazolidin-3-yl)methane

Raúl Salas-Coronado, Sonia A. Sánchez-Ruiz, Juan Carlos Gálvez-Ruiz, and Angelina Flores-Parra*

*Department of Chemistry, Centro de Investigación y de Estudios Avanzados del I.P.N., A.P. 14-740, C.P. 07000 México, D.F., Mexico, D.F.

Abstract

The reagents RMgCl, RLi, NaOMe and amines (R = Me or t-Bu) with bis(4-methyl-5-phenyl-1,3-oxazolidin-3-yl)methane (1) attack nucleophilically at its endo- or exocyclic methylenic groups (C-2 or C-6) giving: 3-ethyl-4-methyl-5-phenyl-1,3-oxazolidine (3), 3-neopentyl-4-methyl-5-phenyl-1,3-oxazolidine (4), 2-[neopentyl-(4-methyl-5-phenylethan-1,3-oxazolidin-3-ylmethyl)amino]-1-phenylpropan-1-ol (6), N-neopentyl norephedrine (7), 3-methoxymethyl-4-methyl-5-phenyl-1,3-oxazolidine (8), N-benzyl-(4-methyl-5-phenyl-1,3-oxazolidin-3-yl)methane (9), 2-chloropropyl-(4-methyl-5-phenyl-1,3-oxazolidin-3-ylmethyl)amine (10), 2-[(benzylamino-methyl)amino]-1-phenylpropan-1-ol (11). A high yield synthesis of 3(H)-4-methyl-5-phenyl-1,3-oxazolidine (5) is also reported.

■ Equilibrium between Bis(1,3-oxazolidin-3-yl)methanes and 3,8-Dioxa-1,6-diazabicyclo[4.4.1]undecanes

Raúl Salas-Coronado, Juan Carlos Gálvez-Ruiz, Carlos Guadarrama-Pérez, and Angelina Flores-Parra*

*Department of Chemistry, Centro de Investigación y de Estudios Avanzados del I.P.N., A.P. 14-740, C.P. 07000 México, D.F., Mexico, D.F.

Abstract

The equilibrium between bis(1,3-oxazolidin-3-yl])methanes (A) and 3,8-dioxa-1,6-diazabicyclo[4.4.1]undecanes (B) is reported. A and B were prepared from formaldehyde and (±)-1-methylethanolamine (1), 2,2-dimethyl-ethanolamine (2), (1S, 2R)-1-methyl-2-phenylethanolamine (3), ethanolamine (4), (R)-2-carboxyethanolamine methyl ester (5), (S)-2-ethylethanolamine (6), (R)-2-phenylethanolamine (7). The equilibrium depends on the substituents. Thermodynamic structures (A) derived from 5 and 7 by slow crystallization are completely transformed into undecanes (B) by an equilibrium asymmetric transformation. Structures were established by ¹H, COSY, HETCOR and NOESY NMR experiments. Preferred conformer of the undecane ring was identified.

■ Synthesis of Metabolites of the Prodrug 2,5-Bis(4-O-methoxyamidinophenyl)furan

Mariappan Anbazhagan, Janelle Y. Saulter, James E. Hall, and David W. Boykin*

*Department of Chemistry, Georgia State University, University Plaza, Atlanta, GA 30303, U.S.A.

Abstract

The synthesis of three metabolites of the prodrug 2,5-bis (4-O-methoxyamidinophenyl)furan (1), 2-(4-hydroxyamidinophenyl)-5-(4-meth- oxyamidinophenyl)furan (M1), 2-(4-amidinophenyl)-5-(4-ethoxyamidino- phenyl)-furan (M3) and 2-(4-amidinophenyl)- 5-(4-hydroxyamidinophenyl)furan (M4), is reported. The key step in each of the syntheses involves the Heck reaction.

■ Oxovanadium Complexes of N-Substituted 3-Hydroxy-2-methyl-4(1H)-pyridinones: Synthesis, Spectroscopic Characterization, and the Insulin-mimetic Activity

Akira Katoh,* Kazutoshi Taguchi, Ryota Saito, Yae Fujisawa, Toshikazu Takino, and Hiromu Sakurai

*Department of Applid Chemistry, Faculty of Engineering, Seikei University, Musashino, Tokyo 180-8633, Japan

Abstract

Five kinds of N-substituted 3-hydroxy-2-methyl-4(1H)-pyridinones, and two kinds of tetradentate ligands, N,N ’-[bis(3-hydroxy-1,4-dihydro-2-methyl-4-oxo-1-pyridyl)hexanoyl- and -octanoyl]-1,5-diamino-3-oxapentanes, were syn-thesized. Treatment of these ligands with VO(acac)₂ in CH₃OH exclusively gave CH₃O-coordinated oxovanadium(V) complexes. On the other hand, treatment with VOSO₄ in H₂O at around pH 10 afforded oxovanadium(IV) complexes. On the basis of the inhibitory effect of oxovanadium(IV) complexes on free fatty acid (FFA) release from rat adipocytes treated with epinephrine in the presence of 0.1% glucose in vitro, it was revealed that some of oxovanadium(IV) complexes show the insulin-mimetic activity.

■ Transformations of Methyl 2-Benzoylamino-2-oxobutanoate. The Synthesis of Oxazolo[4,5-c]quinoline and 1-Substituted 1H-Imidazole-4-carboxylate Derivatives

Urska Bratusek, Simon Recnik, Jurij Svete,* Anton Meden, and Branko Stanovnik*

*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, P.O. Box 537, SI-1000 Ljubljana, Slovenia

Abstract

Methyl 2-benzoylamino-2-oxobutanoate (1) was transformed with aromatic amines (2a-d) into methyl 2-arylamino-2-(benzoylamino)but-2-enoates (3a-d) Cyclization of compounds (3a-c) in polyphosphoric acid affords a mixture of oxazolo[4,5–c]quinoline derivatives (4a-c) and 1-aryl-2-phenyl-5-methyl-1H-imidazole-4-carboxylates (5a-c), while compound 3d gives a mixture of 9-bromo- (4d) and 7-bromooxazolo[4,5–c]quinoline derivative (4d’).

■ Stereoselective Synthesis of trans-4,5-Disubstituted Oxazolidin-2-ones by Intramolecular Conjugate Addition of N-p-Toluenesulfonyl Carbamates

Marco Ciclosi, Cristiana Fava, Roberta Galeazzi, Mario Orena,* José Sepúlveda-Arques, and Maria Eugenia González-Rosende*

*Dipartimento di Scienze dei Materiali e della Terra, Università di Ancona, Via Brecce Bianche, I-60131 Ancona, Italy

Abstract

p-Toluenesulfonyl carbamates (2a-d) were prepared starting from allylic alcohols (3), in which the double bond is conjugated with an electron withdrawing group. In the presence of a catalytic amount of DBU, an intramolecular cyclisation occurred, leading to trans-4,5-disubstituted oxazolidin-2-ones (1a-d) with total stereoselection, which can be precursors of syn-4-hydroxy-3-amino acids.

■ 3-Dimethylhydrazono-1,1,1-trifluoro-2-propanone as a Useful Synthetic Equivalent of Trifluoropyruvaldehyde — Application to Synthesis of Fluorine-containing Heterocycles

Yasuhiro Kamitori*

*Department of Chemical Science and Engineering, Faculty of Engineering, Kobe University, Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

3-Dimethylhydrazono-1,1,1-trifluoro-2-propanone (4) which is easily obtainable from formaldehyde dimethylhydrazone and trifluoroacetic anhydride was found to be an usuful synthetic equivalent of trifluoropyruvaldehyde for the synthesis of fluorine-containing heterocycles. With the use of 4, 4-trifluoromethylimidazoles and 2-trifluoromethylquinoxaline were successfully synthesized.

■ A Facile Synthesis of Indoloquinazolines

Nagappan Arumugam and Panayencheri C. Srinivasan*

*Department of Organic Chemistry, Guindy Campus, University of Madras, Chennai-600 025, India

Abstract

4-[Indol-2’-yl]quinazolines were synthesized from 2-[o-acetamidobenzoyl]indoles and 25% ammonia by heating in a sealed tube at 180 - 200 °C for 2 h.

■ New Pyrrolizidine Alkaloids from Ligularia tsangchanensis

Aimin Tan, Zhengtao Wang,* Hongping He, Mian Zhang, and Xiaojiang Hao

*Department of Pharmacognosy, China Pharmaceutical University, 1 Shen Nong Road, Nanjing 210038, China

Abstract

Two new pyrrolizidine alkaloids named O-acetylyamataimine (1) and O-acetylyamataimine N-oxide (2) along with a known one (3) were isolated from the roots of Ligularia tsangchanensis, and their structures were established by spectroscopic analysis.

■ 9-O-Deacetylumbraculolide A, a New Diterpenoid from the Gorgonian Junceella fragilis

Ping-Jyun Sung* and Tung-Yung Fan

*National Museum of Marine Biology and Aquarium, 2 Houwan Road, Checheng, Pingtung, Taiwan 944, Taiwan, R.O.C.

Abstract

A new briarane-type diterpenoid, 9-O-deacetylumbraculolide A (1), has been isolated from a Formosan gorgonian Junceella fragilis. The structure of this metabolite was established by spectroscopic and chemical methods.

■ Formal Synthesis of Anisomycin

Meng-Yang Chang, Shui-Tein Chen,* and Nein-Chen Chang*

*Institute of Biological Chemistry, Academia Sinica, 128, Yan-Chiu-Yuan Road, Sec II, NanKang, Taipei, 11529, Taiwan, R.O.C.

Abstract

A straightforward formal synthesis of anisomycin has been established starting from trans-4-hydroxyproline.

■ Syntheses of 4-Selenazolones. Hetero Diels-Alder Reaction of the Selenazadienes with DMAD

Mamoru Koketsu,* Futoshi Nada, Takumi Mio, and Hideharu Ishihara*

*Department of Chemistry, Faculty of Engineering, Gifu University, 1-1 Yanagito, Gifu, Gifu 501-1193, Japan

Abstract

Hetero Diels-Alder reaction of selenazadiene with dimethyl acetylenedicarboxylate yielded 4-selenazolone instead of the expected Diels-Alder adduct.

■ A Concise Synthesis of an AHR Endogenous Ligand with the Indolecarbonylthiazole Skeleton

Pawel Grzywacz, Rafal R. Sicinski, and Hector F. DeLuca*

*Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, U.S.A.

Abstract

Short synthesis of an endogenous ligand for the arylhydrocarbon receptor (AHR), 2-(1’H-indole-3’-carbonyl)thiazole-4-carboxylic acid methyl ester (7), has been described. N-Acylation of the L-cysteine methyl ester (4) with indoleglyoxylyl chloride (1) provided glyoxylamide (5) which underwent the TiCl₄-mediated cyclization to thiazoline compound (6), followed by dehydrogenation to the final indole thiazole ketone (7).

■ 1,2,3-Triazole Formation under Mild Conditions via 1,3-Dipolar Cycloaddition of Acetylenes with Azides

Alan R. Katritzky,* Yuming Zhang, and Sandeep K. Singh

*Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, U.S.A.

Abstract

1,3-Dipolar cycloaddition of azides to various electron-withdrawing group substituted acetylenes leading to triazole formation under mild conditions (reaction temperature around 55 °C or below) are reviewed. Furthermore, our efforts to lower the reaction temperature of cycloaddition of acetylenic amides with azides have also been discussed.