HETEROCYCLES

■ Contents

■ Recent Trends in the Synthesis of Enaminones

Al-Shimaa Badran, Najla A. Alshaye, Zeinab Hussain,* Aya Ahmed, and Magdy A. Ibrahim

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Heliopolis 11757, Cairo, Egypt

Abstract

Enaminones are very useful intermediates for building different categories of heterocyclic compounds. Formation of enaminone derivatives was achieved using a variety of compounds such as alcohols, aldehydes, active methyl ketones, active methylene ketones, β-alkoxy ketones, β-diketones, acetoacetamides, Grignard reagents, diazocarbonyl compounds, acetylene derivatives, nitrile derivatives, cyclic compounds, acyl chloride and other enaminones. The present review covers the methods developed for the synthesis of enaminone derivatives.

■ Thiofunctionalized γ-Lactams

Alla I. Vaskevych* and Mykhailo Vovk

*Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Academician Kukhar Str., 5, Kyiv-94, 02660, Ukraine

Abstract

This review summarizes and analyzes literature data concerning the methods of preparation and some aspects of synthetic and biomedical applications of 3-, 4-, and 5-thiosubstituted γ-lactams. The material is systematized for each type of structure according to the prevalence and importance of synthetic methods. Practical application aspects are combined in a section that includes all types of compounds. The bibliography of the review involves 120 sources, from the appearance of the first publications till now.

■ Application of Highly Active TEMPO Derivatives for Electrochemical Analysis

Fumiya Sato, Masayuki Kumano, Haruka Nakano, Kyoko Sugiyama, Tsutomu Fujimura, Katsuhiko Sato,* and Kazuhiro Watanabe*

*Faculty of Pharmaceutical Science, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba, Sendai, Miyagi 981-8558, Japan

Abstract

The electrochemical properties of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) derivatives with improved oxidative capability upon introducing electron-withdrawing groups were evaluated by cyclic voltammetry. Synthesized TEMPO derivatives, including 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (A-TEMPO), 4-trifluoroacetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (F-TEMPO), and dinitroxide condensed with TEPMO exhibiting a 1,2-dicarbonyl structure, 4,4′-[(1,2-dioxo-1,2-ethanediyl)diimino]bis[2,2,6,6-tetramethyl-1-piperidinyloxy] (di-TEMPO), were used as electrocatalysts. Ethanol and vancomycin response currents were compared, demonstrating the potential of specific TEMPO derivatives for quantification. TEMPO derivatives showed enhanced response current increase, suggesting their molecular recognition ability.

■ Chiral Benzimidazolium N-Heterocyclic Carbene Ligands with Hydroxyamide- or Hydroxyalkyl-Functionalized Wingtip for Cu-Catalyzed Asymmetric Allylic Alkylation

Satoshi Sakaguchi* and Shota Takayanagi

*Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan

Abstract

An asymmetric allylic alkylation (AAA) reaction of allyl phosphates with dialkylzinc was studied using a combination of a Cu salt and a bis(hydroxyamide)-functionalized benzimidazolium salt ((R,R; S,S)-L1) derived from (1R, 2R)-(−)-1,2-cyclohexanediamine and (S)-leucinol as a catalyst. Treatment of (E)-cinnamyl diethyl phosphate (1) with Et2Zn under the influence of the Cu(acac)2/(R,R; S,S)-L1 catalytic system under ambient conditions without temperature control afforded (R)-3-phenyl-1-pentene ((R)-2) in 91% yield with 83% ee. The enantioselectvity of the reaction was investigated by evaluating the relationship between the catalyst ee and the product ee in the AAA reaction of 1 with Et2Zn, revealing a clear linear relationship. Investigation of the effect of the leaving group in the allylic substrate on the AAA reaction revealed that using a phosphate leaving group was essential to achieve good catalytic performance. 1,2-Diaminocyclohexane-based bis(N-heterocyclic carbene) azolium ligand L1 exhibited higher reactivity than other chiral azolium ligands having a hydroxyamide functional group. Futhermore, it was found that using the Cu(acac)2/hydroxyalkyl-functionalized benzimidazolium salt L7 system to catalyze the AAA reaction of 1 with Et2Zn led to stereoselectivity reversal to afford (S)-2 in 87% yield with 75% ee. A plausible reaction pathway is proposed.

■ New Reactions of Indoline-2-thiones and Aryl Aldehydes: Microwave-Induced One Step Synthesis of Structurally Diverse Thiopyrano-Diindoles

Krisztián Biró, János Tatai, and Miklós Nyerges*

*Servier Research Institute of Medicinal Chemistry, 7 Záhony utca, 1031, Budapest, Hungary

Abstract

A general and efficient synthesis of 7-aryl-5H-thiopyrano[2,3-b:4,5-b']diindoles and 12-aryl-7,12-dihydro-5H-thiopyrano[2,3-b:6,5-b']diindoles described from easily available, common starting materials in simple, microwave assisted reactions. The selectivity was controlled simply by the choice of base. The explored new reactions with the isolated by-products and intermediates give an interesting, new insight into the chemistry of the thio-oxindoles.

■ Mapping the Antimicrobial Activity of Indoloquinoline and Neocryptolepine Analogues

Katja S. Håheim, Marte Albrigtsen, Kirsti Helland, Jeanette H. Andersen, and Magne O. Sydnes*

*Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, NO-4036 Stavanger, Norway

Abstract

A range of naturally occurring indoloquinolines, such as neocryptolepine and isocryptolepine, have been found to possess antimicrobial and anticancer activity. To broaden our understanding of this class of compound´s biological capacity we herein report the results of a screening campaign of a total of 9 11H-indolo[3,2-c]quinolines, 19 neocryptolepine analogues, and two isocryptolepine analogues towards a panel of both Gram-positive (Enterococcus faecialis, Staphylococcus aureus, and Streptococcus agalactiae) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. The compounds were also tested for their cytotoxicity against human liver cells (HepG2) and human fetal lung fibroblast (MRC-5). Several of the compounds showed antimicrobial and cytotoxic activity, making them interesting for further optimization as antimicrobial or anticancer agents.

■ A Convenient Synthesis of 1,2,4-Triazino[2,3-b]indazol-3-amine Derivatives via Tandem Abnormal Staudinger/Aza-Wittig/Isomerization Reaction

Hai Xie,* Xiu-Ting Qin, Ji Li, Ya-Li Zhang, Jin-Yu Li, and Lei Zhang*

*College of Chemistry and Chemical Engineering, Shanxi Datong University, Datong, 037009, People’s Republic of China

Abstract

A Convenient synthesis route of 1,2,4-triazino[2,3-b]indazol-3-amine analogs by iminophosphoranes with in situ generated from acrylamide containing azide and imino groups and tributylphosphine is herein described. This annulation reaction proceeds through a tandem abnormal Staudinger reaction, intramolecular aza-Wittig reaction and isomerization reaction. This operating procedure has the advantages of simple, cheap and easily available starting materials, mild reaction conditions, no catalyst required, simple operation, and good yield (78-86%). The structures of the synthesized compounds were confirmed by IR, NMR, HRMS and X-ray diffraction.

■ Facile Preparation of the Nootropic Agent IDRA-21 and Related Heterocycles via a One-Pot Iron-Mediated Redox Annulation

Kyosuke Kaneda,* Hirotoshi Kabasawa, Syun Nabeki, Uki Matsui, Hiroki Sugiyama, and Takehiro Yamagishi

*Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, 7-15-4-1, Maeda Teine Sapporo Hokkaido 006-8585, Japan

Abstract

The taking advantage of the redox ability of iron powder allowed us to develop an economical and concise method for the preparation of the 3,4-dihydrobenzothiadiazine 1,1-dioxide (DBTD) and the structurally related heterocycles such as 1,2-dihydroquinazolin-4-one and 1,2,3,4-tetrahydroquinazoline. As an application example, a nootropic agent IDRA-21 was synthesized via one-pot cascade sequences from commercial sources under ambient conditions.