HETEROCYCLES

■ Contents

■ Utility of 2,4-Dioxoesters in the Synthesis of New Heterocycles

Kamal M. Dawood, Hassan Abdel-Gawad, Hanan A. Mohamed, and Bakr F. Abdel-Wahab*

*Applied Organic Chemistry Department, National Research Center, Dokki, Giza, Egypt

Abstract

This review deals with synthesis and reactions of 2,4-dioxoesters. Some of these reactions have been applied successfully to the synthesis of biologically important compounds. The data published over the last years on the methods of synthesis and chemical properties of 2,4-dioxoesters are reviewed here for the first time.

■ Artificial Macrosphelides as a Novel Apoptosis-Inducing Compound

Yuji Matsuya* and Hideo Nemoto

*Faculty of Pharmaceutical Sciences, Toyama University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan

Abstract

Natural 16-membered macrolide compounds, macrosphelides, have recently been disclosed to exert an apoptosis-inducing effect against human lymphoma U937 cells. In this review, molecular design, syntheses, and biological evaluation of artificial macrosphelides are surveyed, focusing on their apoptosis-inducing activity.

■ A [2]Rotaxane Containing N,N-Dialkylammonium Ion and N-Alkylaniline Centers. Translational Isomerism, and Specific N-Acylations

Yuji Tokunaga,* Masanori Kawabata, Yuji Yamauchi, and Naoki Harada

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

Abstract

This paper describes the molecular shuttling and specific N-acylations of a [2]rotaxane featuring an encircling crown ether unit and both N-alkylaniline and N,N-dialkylamine centers on its dumbbell-shaped component. The crown binds predominantly to the dialkylammonium center under neutral conditions. Reactions with acid anhydride in nonpolar solvents and in the absence or presence of a weak base resulted in the N-acylations occurring mainly at the aniline moiety, and selective N-acylations of the dialkylamine unit occurred in polar solvents in the presence of strong bases.

■ An Improved Synthesis of Arylboronates toward Twenty Novel 1,3-Disubstituted 4-Amino-1H-pyrazolo[3,4-d]pyrimidine Analogs

Masato Oikawa*

*Yokohama City University, Seto 22, Kanazawa-ku, Yokohama , Kanagawa 236-0027, Japan

Abstract

By developing an improved procedure for arylboronates, twenty 1H-pyrazolo[3,4-d]pyrimidine analogs were efficiently synthesized as a source of a potent kinase inhibitor.

■ Synthetic Studies on Callipeltins: Stereoselective Syntheses of (3S,4R)-3,4-Dimethyl-L-pyroglutamic Acid and Fmoc-D-allothreonine from Serine Derivatives

Hiroyuki Konno,* Yoko Takebayashi, Kazuto Nosaka, and Kenichi Akaji

*Yamagata University, 3-16 Jonan 4-Chome, Yonezawa 992-8510, Japan

Abstract

The non-proteinogenic amino acids contained in callipeltins, (3S, 4R)-3, 4-dimethyl-L-pyroglutamic acid and D-allothreonine, were synthesized from D- or L-serine. The stereoselective synthesis of two methyl groups of (3S, 4R)-3, 4-dimethyl-L-pyroglutamic acid was accomplished by diastereoselective hydrogenation and alkylation. Kinetic epimerization of the C-4 methyl substituent followed by Boc-deprotection with 10% TFA gave the desired (3S, 4R)-3, 4-dimethyl-L-pyroglutamic acid as a single isomer.

■ The Synthesis of Novel 2,4,6-Trisubstituted 1,3,5-Triazines: A Search for Potential MurF Enzyme Inhibitors

Izidor Sosič, Bogdan Štefane,* Andreja Kovač, Samo Turk, Didier Blanot, and Stanislav Gobec*

*Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, 1000 Ljubljana, Slovenia

Abstract

A series of new 2,4,6-trisubstituted 1,3,5-triazines, possessing a variety of substituents (–OH, –SH, –OMe, –Cl, –HNR, –SR and amino acid moieties), were synthesized and evaluated for the inhibition of the bacterial peptidoglycan biosynthesis enzyme MurF. Ethoxycarbonyl isothiocyanate successfully reacted with a variety of amidines, enabling an approach to 6-substituted-4-thioxo-1,3,5-triazin-2-ones. Also, a representative set of 2-thio-, 2-amino-, and 2-oxo-substituted 1,3,5-triazines was synthesized by the SNAr reaction, employing 2,4,6-trichloro-1,3,5-triazine and 2-chloro-4,6-dimethoxy-1,3,5-triazine as the starting materials. One compound displayed notable inhibitory activity against MurF from Escherichia coli.

■ Exploration of Braverman Reaction Chemistry. Synthesis of Tricyclic Dihydrothiophene Dioxide Derivatives from Bispropargyl Sulfones

Ken S. Feldman* and Brandon R. Selfridge

*Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, U.S.A.

Abstract

The base-mediated bicyclization of unsymmetrical bispropargyl sulfones furnishes varying yields of dihydroisobenzothiophene dioxides through a presumed diradical intermediate. Attempts to trap a putative thiophene dioxide intermediate via Diels-Alder reaction with a pendant alkyne were not successful.

■ Synthesis of Arnoamine B

Shinsuke Nakahara,* Toshiyuki Sadachi, and Akinori Kubo

*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

The synthesis of arnoamine B (2), which inhibits the catalytic activity of topoisomerase II and exhibits selective cytotoxicity against human tumor cell lines, was achieved in six steps from 5-methoxy-6-nitroindole (3) in 33 % overall yield.

■ A Synthetic Study of Dibenzo-Aromatic Macrolactams

David P. Brown* and Thomas Wong

*Department of Chemistry, St. John’s College of Liberal Arts and Sciences, St. John's University, 8000 Utopia Parkway, Jamaica, New York 11439, U.S.A.

Abstract

Efforts to generate benzenoid macrolactams in the development of hybrid molecules as New Chemical Entities are described. The olefin metathesis protocol was adopted in facilitating the cyclization process.

■ New, Facile Synthesis of 3,3-Disubstituted Phthalides Based on the Reaction of α-Substituted 2-Lithiostyrenes with Carbon Dioxide

Kazuhiro Kobayashi,* Taketoshi Kozuki, Shuhei Fukamachi, and Hisatoshi Konishi

*Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

A new method to prepare 3,3-disubstituted phthalides [isobenzofuran- 1(3H)-ones] from α-substituted 2-bromostyrenes has been developed. The reaction of α-substituted 2-lithiostyrenes, generated in situ by bromine-lithium exchange between α-substituted 2-bromostyrenes and butyllithium, with carbon dioxide gave the corresponding lithium 2-vinylbenzoates, which upon treatment with concentrated hydrochloric acid afforded the desired products in one pot.

■ A Non-Catalyst Method for the Synthesis of Bis-4-aryl-3,4-dihydropyrimidones (thiones) under Solvent-Free Conditions

Chhanda Mukhopadhyay* and Arup Datta

*Department of Chemistry, University of Calcutta, 92, APC Road, Kolkata-700009, India

Abstract

Three component coupling of an aromatic dialdehyde, a β-keto ester or β-diketone and urea or thiourea (1:2.2:2.5 mol ratios) in one–pot under solvent-free conditions without any catalyst produced the bis-dihydropyrimidones (thiones) in a microwave oven. This is therefore a “green” synthesis of the title compounds under the said conditions.

■ Preparation of New Nitrogen-Bridged Heterocycles. 68. One-Pot Synthesis of 4-Substituted 5-Acylthieno[3,2-d]thiazole Derivatives

Akikazu Kakehi,* Hiroyuki Suga, Yukihisa Okumura, and Takashi Nishi

*Department of Chemistry and Material Engineering, Faculty of Engineering, Shinshu University, 4-17-1 Wakasato, Nagano 380-8553, Japan

Abstract

The reactions of 5-acyl-3-(1-pyridinio)thiophene-2-thiolates with dimethyl acetylenedicarboxylate in xylene at the reflux temperature afforded the corresponding 2-unsubstituted 5-acylthieno[3,2-d]thiazoles in 25―69% yields together with dimethyl phthalate as another fragmentation product. In a few reactions, the unexpected products, dimethyl 2-[2-acylthieno[2’,3’:2,3]-1,4-thiazino[4,5-a]pyrrol-8-ylidene]succinate derivatives, were also isolated, though their yields were very low.

■ Facile Synthesis of Imidazo[1,2-a]pyridines via Tandem Reaction

Jiong Jia, Yan-Qing Ge, Xu-Tang Tao,* and Jian-Wu Wang*

*School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China

Abstract

An efficient method for the synthesis of 5,6,7-trisubstituted imidazo[1,2-a]pyridines was developed. The products were obtained in good yields under mild conditions.