HETEROCYCLES

■ Contents

■ A New Synthetic Entry to Furofuranoid Lignans, Methyl Piperitol and Fargesin

Hidemi Yoda,* Yuji Suzuki, Daisuke Matsuura, and Kunihiko Takabe

*Department of Molecular Science, Faculty of Engineering, Shizuoka University, 3-5-1 Johoku, Hamamatsu 432-8561, Shizuoka, Japan

Abstract

An efficient and general process is described for the preparation of the unsymmetrically substituted diequatorial and axial-equatorial furofuran lignans, methyl piperitol and fargesin. The synthetic strategy is based on a stereoselective manner by nucleophilic addition of organometallic reagent to the monoterpene lactone elaborated from dihydroxyacetone dimer followed by condensation with the corresponding aromatic aldehyde counter part.

■ Conformational Analysis of Dinaphthalene-1-carboxylate Complex of Sn^IV(tetraphenylporphyrin)

Hajime Iwamoto and Yoshimasa Fukazawa*

*Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, 739-8526, Japan

Abstract

Conformational analysis of dinaphthalene-1-carboxylate complex of Sn^IV(tpp) (1) in solution was carried out using temperature dependent ¹H NMR spectra and chemical shift simulation method. It was found that two vertical conformers are in equilibrium in solution for 1.

■ Studies toward the Synthesis of Furanocembrane Bipinnatin J: Synthesis of a 2,3,5-Trisubstituted Furfuryl Ether Intermediate

Masayoshi Tsubuki,* Kazunori Takahashi, Ken Sakata, and Toshio Honda*

*Faculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan

Abstract

Synthesis of 2,3,5-trisubstituted furfuryl ether (29), a potential intermediate in a synthetic approach to bipinnatin J, was achieved by a combination of etherification and Stille cross-coupling reaction. Unexpectedly, an intramolecular coupling reaction of 29 proceeded through S_N2’ substitution to give 15-membered furfuryl ether (30). Formation of γ-butenolide (34) was also accomplished by a ruthenium-catalyzed carbonylation of allenic alcohol (33).

■ Antitumor Agents 238. Anti-tubulin and in vitro Cytotoxic Effects of N-Substituted Allocolchicinoids

Kyoko Nakagawa-Goto, M. Katherine Jung, Ernest Hamel, Chin-Chung Wu, Kenneth F. Bastow, Arnold Brossi, Shunsaku Ohta, and Kuo-Hsiung Lee*

*Natural Products Laboratory, School of Pharmacy, University of North CarolinaChapel Hill, North Carolina 27599, U.S.A.

Abstract

(-)-N-Substituted colchinol methyl ethers (6-10) and N-alkyl HCl salts (8a—10a) were synthesized from (-)-colchicine (1). The new compounds were evaluated for in vitro cytotoxic activity against five human tumor cell lines and for inhibition of tubulin polymerization. The new carbamate (6) and amide (7) showed 10-fold stronger activity against human tumor cell line replication than the amines (8—10). The corresponding HCl salts (8a—10a) generally showed decreased activity. Compounds (6) and (7) also exerted strong inhibitory effects on tubulin polymerization. All of the colchinol methyl ethers showed essentially equal cytotoxic effects against MDR-resistant (KB-V) and non-resistant (KB) cells, while the potency of colchicine was decreased 100-fold against KB-V cells.

■ Syntheses, Spectroscopic Properties, and Cu(I) Complexes of All Possible Symmetric Bi-1,10-phenanthrolines

Shinji Toyota,* Akito Goto, Keiko Kaneko, and Takumi Umetani

*Department of Chemistry, Faculty of Science, Okayama University of Science, 1-1 Ridaicho, Okayama 700-0005, Japan

Abstract

All possible symmetric bi-1,10-phenanthrolines (biphens) were synthesized by Ni-catalyzed coupling of corresponding halo-1,10-phenanthrolines. Their absorption and emission spectra were compared with those of phenanthroline as the reference compound. The spectral feature is explained by the molecular conformation, namely, coplanar 2,2’- and 3,3’-biphens and nearly bisected 4,4’- and 5,5’-biphens. The effects of additives, H⁺ or Zn²⁺, on the electronic spectra varied depending on the biphen ligand. The 2,2’-ligand formed a helical complex with Cu⁺ ions in a 2:2 ratio as revealed by spectroscopic titration and X-Ray analysis.

■ Absolute Stereo-structure of Kendarimide A, a Novel MDR Modulator, from a Marine Sponge

Naoyuki Kotoku, Liwei Cao, Shunji Aoki, and Motomasa Kobayashi*

*Graduate School of Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka 565-0871, Japan

Abstract

The absolute stereostructure of two N-methylcysteines in kendarimide A (1), a novel linear peptide reversing multidrug resistance (MDR) mediated by P-glycoprotein, was determined by comparison with synthetic model compounds. For this purpose, four diastereomers (17a-d) of the C-terminal tetrapeptides in kendarimide A (1), containing L,L-, L,D-, D,L-, D,D-N-methylcysteinyl-N-methylcysteine, were synthesized. The absolute configuration of both the two adjacent N-methylcysteines in 1, which form an eight-membered disulfide ring (ox-[MeCys-MeCys]), was elucidated to be L-configuration by comparison of the NMR spectral data of the four model tetrapeptides with that of kendarimide A (1).

■ Synthesis of 2-Substituted Thiopyrano[3,2-b][1,4]benzoxazine-2,3-dicarboxylic Acid Dimethyl Esters

Sukanta Kamila, Hongming Zhang, Dumming Zhu, and Edward R. Biehl*

*Southern Methodist University, Department of Chemistry, Dallas, TX 75275, U.S.A.

Abstract

The titled compounds were prepared by the reaction of 4H-benzo[1,4]oxazin-3-thiones with dimethyl acetylenedicarboxylate. The 3-thione intermediates were obtained by treating 4-methyl-4H-benzo[1,4]oxazin-3-ones with P₂S₅ followed by piperidine-mediated condensation of the resulting 4-methyl-4H- benzo[1,4]oxazin-3-thiones with various aromatic and heteroaromatic aldehydes. Oxazine-3-thiones, however, failed to react with several benzyne intermediates.

■ Nitrone 1,3-Dipolar Cycloadditions to Enol Ethers Catalyzed by Lewis Acids. An Access to β-Amino Acids

Branislav Dugovic, Tomás Wiesenganger, Lubor Fisera,* Christian Hametner, and Nada Prónayová

*Department of Organic Chemistry, Slovak University of Technology, Bratislava 812 37, Slovakia

Abstract

The stereoselectivity of nitrone cycloaddition with enol ethers (2 and 4) depends upon the nature of the Lewis acid. The 1,3-dipolar cycloaddition of nitrones (1, 6 and 8) with enol ether (2) under the catalysis of AlMe₃ and Et₂AlCl proceeded diastereoselectively; whereas nitrone substitution with TBDPS reverses the diastereoselectivity of the cycloaddition. The oxidative ring-opening of isoxazolidines (3 and 9) with the treatment of benzyl bromide results new β-amino acid esters (11, 13 and 15).

■ Briarane Diterpenes from a Gorgonian Briareum Sp.

Tetsuo Iwagawa,* Kazutaka Babazono, Munehiro Nakatani, Matsumi Doe, Yoshiki Morimoto, and Kaoru Takemura

*Department of Chemistry and Bioscience, Faculty of Science, Kagoshima University, 1-21-35 Korimoto, Kagoshima 890-0065, Japan

Abstract

Eleven new briarane diterpenes have been isolated from a gorgonian Briareum sp., collected in the area of Bonotsu, Kagoshima Prefecture. Their structural elucidation and cytotoxicity tests toward Vero and MDCK cells were performed.

■ Synthesis of 2-(3-Iminoisoindolin-1-ylidene)carboxylate Derivatives by Reactions of Ester Magnesium Enolates with Phthalonitrile Derivatives

Kazuhiro Kobayashi,* Kiyoto Honma, Shizuka Kondo, Osamu Morikawa, and Hisatoshi Konishi

*Department of Materials Science, Faculty of Engineering, Tottori University, Koyama-minami, Tottori 680-8552, Japan

Abstract

Efficient preparation of the title iminoisoindolines and related derivatives can be achieved via the coupling between ester magnesium enolates and one of two nitrile moieties of phthalonitriles, followed by the attack of the resulting imino anion to the second nitrile carbon.

■ Syntheses and Tautomerisations of Amino-substituted and Pyrimidine-annulated Pyrrolobenzodiazepines

Andreas Schmidt,* Abbas Gholipour Shilabin, and Martin Nieger

*Clausthal University of Technology, Institute of Organic Chemistry, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany

Abstract

Different tautomers of 11-amino-substituted pyrrolo[2,1-c][1,4]benzodiazepines and 2-substituted 4,7a,12b-triazadibenzo[e,g]azulene-1,8-diones were formed depending on the substitution pattern. Syntheses, spectroscopic investigations and an X-Ray analysis are presented.

■ Two New Alkaloids from Dendrobium chrysanthum

Li Yang, Chaofeng Zhang, Hong Yang, Mian Zhang, Zhengtao Wang,* and Luoshan Xu

*Department of Pharmacognosy, China Pharmaceutical University, Naning 210038, China

Abstract

Two new alkaloids, trans- and cis-dendrochrysanines (1 and 2) were isolated from the stems of Dendrobium chrysanthum Wall. and their structures were identified as (2S)-N-trans-cinnamoyl-2-oxopropyrrolidine (1) and (2S)-N-cis-cinnamoyl-2-oxopropyrrolidine (2), respectively, on the basis of spectroscopic methods.

■ A Synthesis and Reactivity of 1,4-Dihydro-4-thioxo-3-quinolinesulfonamides

Leszek Skrzypek

*Department of Organic Chemistry, The Medical University of Silesia, Jagiellonska 4, 41-200 Sosnowiec, Poland

Abstract

4-Chloro-3-quinolinesulfonamides (1) were transformed to 1,4-dihydro- 4-thioxo-3-quinolinesulfonamides (2) which methylation gave 4-methylthio-3-quinolinesulfonamides (3). Oxidation of sulfonamides (2) with hydrogen peroxide provided 1,4-dihydro-4-oxo-3-quinolinesulfonamides (4).

■ A Phosphino-substituted Isoindole Obtained by Cyclization of a Thiourea Derivative

Jorge R. Angulo-Cornejo, Arancha Carbayo, Elva Cueva-Talledo, José V. Cuevas, Gabriel García-Herbosa,* and Asunción Muñoz

*Area of Inorganic Chemistry, Faculty of Sciences, University of Burgos, Misael Bañuelos Square, 09001 Burgos, Spain

Abstract

A phosphorous functionalized isoindole derivative has been formed in the cyclization reaction of 3-chloro-p-tolylmethylene-1,1-diethylthiourea with lithium diphenylphosphide. The reaction involves thiourea desulfuration and C-S to P-S sulfur transfer.

■ Hypervalent Iodine(III) Sulfonate Mediated Synthesis of 5-Benzoyldihydro-2(3H)-furanone in Ionic Solvent

Rei-Sheu Hou, Huey-Min Wang, Yu-Chien Lin, and Ling-Ching Chen*

*Graduate Institute of Pharmaceutical Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.

Abstract

The room temperature ionic liquid, n-butylpyridinium tetrafluoroborate (BPyBF₄) is used as a “green” recyclable solvent for the reaction of 4-benzoylbutyric acid with [hydroxy-(2,4-dinitrobenzenesulfonyloxy)iodo]- benzene (HDNIB) to prepare 5-benzoyldihydro-2(3H)-furanone.

■ Molybdatophosphoric Acid/NaNO₂/Wet SiO₂ as an Efficient System for Oxidation of 1,4-Dihydropyridines under Mild and Heterogeneous Conditions

Khodabakhsh Niknam,* Mohammah Ali Zolfigol,* Seyed Mehdi Razavian, and Iraj Mohammadpoor-Baltork

*Chemistry Department, Faculty of Sciences, Persian Gulf University, Bushehr 75168, Iran

Abstract

A combination of molybdatophosphoric acid (H₃PMo₁₂O₄₀.xH₂O) and sodium nitrite in the presence of wet SiO₂ was used as an effective oxidizing agent for the oxidation of 1,4-dihydropyridines to the corresponding pyridine derivatives under mild and heterogeneous conditions in excellent yields.

■ A New Flavone from Lycopodium japonicum

Jian Yan, Lirong Sun, Xianming Zhang, and Minghua Qiu*

*State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650204, China

Abstract

A new flavone, lycopodone (1), together with other three known flavonoids tricin (2), tricetin 3’,4’,5’-OMe (3), 5,7,4’-trihydroxy-3’- methoxy flavone (4), were isolated from the fern Lycopodium japonicum. The structure of 1 was established on the basis of spectral measures. Compounds (1) and (2) showed moderate antitumor activity.

■ Nucleoside Chemistry in Crop Protection

Clemens Lamberth

*Chemistry, Crop Protection Research, Syngenta AG, Schwarzwaldallee 215, CH-4002 Basel, Switzerland

Abstract

This review aims to give an overview of the significance of nucleosides in crop protection. The main herbicidally, fungicidally and insecticidally active nucleoside classes are presented together with their synthetic issues, mode of action and biological efficacy.

■ Synthesis of Benzo[c]phenanthridine Alkaloids Using a Palladium-catalyzed Aryl-Aryl Coupling Reaction

Takashi Harayama

*Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-naka 1-1-1 , Okayama 700-8530, Japan

Abstract

A synthesis of (fully aromatized) benzo[c]phenanthridine alkaloids was accomplished using an intramolecular palladium-catalyzed aryl-aryl coupling reaction of halo- or triflyloxyarenes.