HETEROCYCLES

■ Contents

■ Recent Advances in the Total Synthesis of Clavilactones

Akihiro Ogura and Ken-ichi Takao*

*Department of Applied Chemistry, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, Japan

Abstract

Clavilactones are meroterpenoids containing a 10-membered carbocycle fused to an α,β-epoxy-γ-lactone and a hydroquinone or benzoquinone. This review describes the total synthesis of clavilactones achieved by four research groups, focusing on their innovative synthetic strategies.

■ Reactivity of 4,6-Dimethoxy Activated Benzimidazoles

Mahiuddin Alamgir, Glenn C. Condie, Vesna Martinovic, Joanne Wood, Mohan Bhadbhade, Naresh Kumar, and David StC. Black*

*School of Chemistry, The University of New South Wales, Sydney 2052, Australia

Abstract

4,6-Dimethoxy-2-substituted-benzimidazoles undergo formylation, acylation, nitration and bromination at C7. The 7-carbaldehydes can be reduced to the corresponding hydroxymethyl compounds. Benzimidazole-2-carbaldehydes can be prepared by oxidation of 2-methyl- and 2-styryl-benzimidazoles. N-Methylation and N-allylation have also been investigated and lead to isomeric mixtures of 4,6- and 5,7-dimethoxybenzimidazoles. In general the nucleophilic capacity of the activated benzimidazoles is weaker than that of the related activated indoles, but still provides synthetic routes to a range of new heterocyclic structures.

■ Facile Preparation of 3,4-Benzocoumarins from 2-Arylbenzoic Acids with NCS and Nai

Momoko Nakamura and Hideo Togo*

*Graduate School of Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan

Abstract

Treatment of 2-arylbenzoic acids with N-chlorosuccinimide (NCS) and NaI at 70 °C under fluorescent lighting condition gave the corresponding 3,4-benzocoumarins in good yields under transition-metal-free condition. It was found that the reactivity of NCS with NaI for the formation of 3,4-benzocoumarins from 2-arylbenzoic acids was as high as that with NIS. Thus, the formation of carboxyl radicals and their cyclization onto an aromatic ring from 2-arylbenzoic acids with much less expensive NCS and NaI, than NIS could be successfully carried out to form 3,4-benzocoumarins.

■ Structural and DFT Study of 1-(3-Amino-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-3,4-dichloro-1H-pyrrole-2,5-dione: Hypothesis for the Ring Closure

Bader A. Salameh* and Murad A. AlDamen*

*Department of Chemistry, Faculty of Science, the Hashemite University, Zarqa 13133, Jordan.

Abstract

The reaction of 2,3-dichloromaleic anhydride with 2,3-diamino-1,4-naphthoquinone was studied and afforded to 1-(3-amino-1,4-dioxo-1,4- dihydronaphthalen-2-yl)-3,4-dichloro-1H-pyrrole-2,5-dione (3). Experimental techniques (NMR and single-crystal structures) confirmed the structure of 3. The study was extended to explore the failure of the intramolecular cyclization of 3 to the imidazole ring. Density Functional Theory at level B3LYP/6-31G(d,p) of theory were used to examine the optimized molecular geometry and to understand the reaction mechanism which reveals that the failure of cyclization is possibly due to positive charge of the amine in addition to the high repulsion between the naphthoquinone and the maleimide oxygens.

■ Improved Synthesis of Cyclohexane-Backbone Iridium-Complexes of Quinoline-Phosphine and Their Applications in Asymmetric Hydrogenation

Qibin Liu*

*R&D department, Dalian Allychem Co. Ltd, No 5 of Jinbin Road, Jinzhou New District 116620, China

Abstract

The iridium-complexes 3 and 4 with cyclohexane-backbone derived from quinoline were easily synthesized. The key step is cis/trans stereoselective reduction of 2-(quinolin-2-yl)cyclohexanone 5 to trans-2-(quinolin-2-yl)cyclohexanol 6 using Al(Oi-Pr)3/i-PrOH and the following diastereomeric optical resolution of racemic 6 using 0.50 equiv (S)-mandelic acid in EtOAc. These complexes were used in the asymmetric hydrogenation of (E)-1,2-diphenylpropene with up to 13% ee/48% conv. using 3 and 35% ee/9% conv. using 4. For the hydrogenation of (2H-chromen-3-yl)methanol, up to 80% ee/95% yield and 72% ee/96% yield were achieved. The same configuration of the products by using 3 and 4 suggested that the absolute configuration was controlled by the configuration of the stereogenic quinolinyl-bearing carbon of the complexes.

■ Synthetic Approach for Building Heteroannulated Furo[3,2-g]chromenes Using 4,9-Dimethoxy-5-oxo-5H-furo[3,2-g]chromene-6-carbonitrile and Cyclic Carbon Nucleophiles

Magdy A. Ibrahim,* Sami A. Al-Harbi, and Esam S. Allehyani

*Department of Chemistry, Faculty of Education, Ain Shams University, Roxy, Cairo 11711, Egypt

Abstract

A novel series of polyfused heterocyclic systems containing furo[3,2-g]chromenes were efficiently synthesized. The reactivity of 4,9-dimethoxy-5-oxo-5H-furo[3,2-g]chromene-6-carbonitrile (1) was studied towards a variety of carbon nucleophilic reagents such as heterocyclic enols, heterocyclic enamines and cyclic active methylene compounds. Treatment of carbonitrile 1 with 4-hydroxycoumarin, 4-hydroxy-1-methylquinolin-2(1H)-one (3), 2-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one (4) afforded furodichromenopyridine 2, furochromenonaphthyridine 5, furochromenodipyridopyrimidine 6. Reaction of carbonitrile 1 with 4(6)-aminouracil and 5-amino-3-methyl-1H-pyrazole proceed through ring opening followed by cycloaddition into the nitrile group giving pyrido[2,3-d]pyrimidine 7 and pyrazolo[3,4-b]pyridine 8. Also, reaction of carbonitrile 1 with 5-amino-2,4-dihydro-3H-pyrazol-3-one (9), 2-(phenylimino)-1,3-thiazolidin-4- one (11), thiobarbituric acid and cyclohexane-1,3-dione produced the novel annulated furo[3,2-g]chromenes 10, 12-14, respectively. Cyclohexane-1,2-dione reacted with carbonitrile 1 in 1:2 molar ratio afforded bis-(furochromeno)[1,10]phenanthroline 15. The prepared compounds were screened in vitro for their antimicrobial activity and some of them appeared notable activity against the tested microorganisms.

■ Reactivity of the Enamine Tautomer of a Cyclic 1,4-Diazadiene with a Diketone

Kazuhide Nakahara,* Koki Yamaguchi, and Hisao Kansui

*Department of Integrative Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1, Nagaotoge-cho, Hirakata-shi, Osaka 573-0101, Japan

Abstract

Cyclic 1,4-diazadiene (2,3-dihydro-5-methyl-6-phenylpyrazine) and diketone (1-phenyl-1,2-propanedione) yielded two products via dehydration–condensation of the diamine and diketone moieties when a mixture of H2O and MeOH was used as the solvent. The structures of the new products were established by 2D NMR analysis. Single-crystal X-ray structural characterization and density functional theory calculations allowed us to determine that this reaction took place via reaction of the enamine tautomer.

■ Rumphellolide K, a Novel C-3/8 Ether Linkage Caryophyllane from Rumphella antipathes

Hsu-Ming Chung, Yu-Ming Chang, Wei-Hsien Wang, Jih-Jung Chen, Tsong-Long Hwang,* and Ping-Jyun Sung*

*National Museum of Marine Biology and Aquarium, Pingtung 944401, Taiwan

Abstract

Chemical examination of Rumphella antipathes, collected in the waters of Taiwan, led to the isolation of a novel caryophyllane sesquiterpenoid, rumphellolide K (1), with a C-3/8 ether linkage. The structure of 1 was established by spectroscopic analysis and this compound displayed inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.