HETEROCYCLES

■ Contents

■ Chemistry of 2,5-Diketopiperazine and Its Bis-Lactim Ether: A Brief Review

Shigeki Sano* and Michiyasu Nakao

*Molecular Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan

Abstract

2,5-Diketopiperazines have attracted much attention because of their biological activities and molecular structure characteristics. Bis-lactim ethers derived from these 2,5-diketopiperazines include well-known organic molecules such as Schöllkopf chiral auxiliaries, which are used in asymmetric synthesis of α-amino acids. In this article, we briefly discuss the chemistry of both heterocyclic compounds.

■ New Synthetic Approach Leading to 1- or 1,3-Disubstituted 2-Thiouracil-5-carboxylates via Dimroth Rearrangement of Isomeric Thiazines

Veronika Hladíková, Richard Kammel, and Jiří Hanusek*

*Institute of Organic Chemistry and Technology, University of Pardubice, Studentská 573, Pardubice, 532 10, Czech Republic

Abstract

Methyl 1-substituted and 1,3-disubstituted-2-thiouracil-5-carboxylates (3b-d) were prepared using new synthetic approach involving base-catalyzed cyclization of easily available S-[3-methoxy-2-(methoxycarbonyl)-3-oxoprop-1-en-1-yl]isothiuronium salts (1a-d) to methyl 2-substituted imino-4-oxo-3,4-dihydro-2H-1,3-thiazine-5-carboxylates (2a-d) and their nucleophile-assisted Dimroth rearrangement to methyl 1-substituted and 1,3-disubstituted-2-thiouracil-5-carboxylates (3b-d). Cyclization step is very sensitive towards the base used – e.g. 1a react with stronger bases or bases in excess to give bis-[3-methoxy-2-(methoxycarbonyl)-3-oxoprop-1-en-1-yl]sulfide (4) as the only isolated product.

■ A Simple, Efficient and Green Procedure for Knoevenagel Condensation in Hydroxy-Functionalized Ionic Liquids

Yuting Liu, Rong Li, and Yanjun Xing*

*College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Renmin Road 2999#, Shanghai 201620, China

Abstract

An efficient and simple Knoevenagel condensation catalyzed by hydroxy-functionalized ionic liquids proceeded smoothly in high yields under ambient and solvent-free conditions. The condensation procedures of aryl aldehydes and 2,4-thiazolidinedione was involved in hydrogen bonding interactions between the hydroxy groups of the ILs and the carbonyl group of the aldehyde. The ionic liquids can be reused for five times without significant loss in activity.

■ Transformation of Benzoxazinone Derivatives to Some Interesting Heterocyclic Compounds with Expected Biological Activity

Magda I. Marzouk,* Thoraya A. Farghaly, Maher A. El-Hashash, Soheir A. Shaker, and Shadia M. Hussein

*Department of Chemistry, Faculty of Science, Ain Shams University, Abbassia 11566, Cairo, Egypt

Abstract

The newly synthesized iodobenzoxazinone derivative was reacted with benzoyl hydrazide, sodium azide, hydrazine hydrate, p-toluidine, hydroxylamine hydrochloride and formamide to give (quinazolinyl)benzamide, (oxazinyl)benzohydrazide, imidazolecarboxamide, (tetrazolyl)benzoic acid, 3-aminoquinazolinone, p-toylquinazolinone, hydroxyquinazolinone and quinazolinone derivatives respectively. Reaction of hydroxyquinazolinone with acetic anhydride and ethyl chloroacetate afforded (quinazolinyl)acetate and ethyl (quinazolinyloxy)acetate derivatives. The quinazolinone reacted with benzoyl chloride, acetyl chloride and ethyl chloroacetate to afford N-(3-benzoyl-dihydroquinazolinyl)-N-phenylbenzamide, 3-acetylquinazolinone and ethyl quinazolinylacetate respectively. The acetohydrazide which was synthesized from the reaction of the ethyl quinazolinyl acetate with hydrazine hydrate was used as a starting material for preparation of some other quinazolinone derivatives. The newly synthesized compounds were characterized by spectroscopic tools and some of them were screened for antibacterial and antifungal activity.

■ Structure and Absolute Configuration of the 11-Noriridoid “Chapingolide”

Matilde Villa-García, María Amparo Borja-De-La-Rosa, Holber Zuleta-Prada, Rubén A. Toscano, and Benito Reyes-Trejo*

*Laboratorio de Productos Naturales, Área de Química, Departamento de Preparatoria Agrícola, Universidad Autónoma Chapingo, Apartado Postal 74, Oficina de Correos Chapingo, Km 38.5 Carretera México-Texcoco, Chapingo, México 56230, México

Abstract

The natural product chapingolide {systematic name: (4aS, 7R, 7aR)-7-hydroxy-7-(hydroxymethyl)-4,4a,7,7a-tetrahydrocyclopenta[c]pyran-3(1H)-one}, C9H12O4, (1), is a new 11-nor-iridoid isolated from Calatola mollis Standl. The colourless compound has a bicyclic structure with an endo double bond in the five-membered ring. The absolute configuration was established by mean of the anomalous dispersion of the oxygen scatters present in the structure.

■ Cu-Mediated Oxidative Dimerization of Skatole to Tryptanthrin, an Indolo[2,1-b]quinazolone Alkaloid

Tomoki Itoh, Takumi Abe, Shuhei Nakamura, and Minoru Ishikura*

*School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract

A one-pot conversion of skatole to tryptanthrin, an indolo[2,1-b]quinazoline alkaloid, was achieved by Cu-mediated oxidation.

■ A New N-Glucosylated Indole Alkaloid and a New O-Serine Glycoside from Berberis koreana

Ki Hyun Kim, Hee Rae Kang, Eunjung Moon, Sang Un Choi, Ki Sung Kang, Sun Yeou Kim, and Kang Ro Lee*

*Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, 300 Chunchun-dong, Jangan-ku, Suwon 440-746, Korea

Abstract

A new N-glucosylated indole alkaloid, 1-(1-β-glucopyranosyl)-3-(hydroxymethyl)-1H-indole (1) and a new O-serine glycoside, 3-O-α-D-xylopyranosyl-L-serine methyl ester (2), along with five known compounds (3-7) were isolated from the trunk of Berberis koreana. The structures of the new compounds were elucidated by 1D and 2D NMR data analysis and chemical reaction. Compounds 1, 2, 4, 5, and 7 reduced nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, a microglial cell line. In addition, compounds 4 and 5 showed moderate anti-proliferative activity against A549 and HCT-15 cell lines.

■ Synthesis of 10-Substituted Pyrido[2,3-b][1,8]naphthyridin-5(10H)-ones (Anthyridin-5(10H)-ones) Based on the Reaction of Bis(2-chloropyridin-3-yl)methanones with Primary Amines

Kazuhiro Kobayashi,* Toshihide Komatsu, Shohei Yuba, Yuuki Chikazawa, and Miyuki Tanmatsu

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

Abstract

An efficient method for the preparation of 10-substituted pyrido[2,3-b][1,8]naphthyridin-5(10H)-ones, utilizing the reaction of bis(2-chloropyridin-3-yl)methanone, derived from 2-chloropyridine and 2-chloropyridine-3-carbaldehyde, with primary amines under heating at 80 ˚C, followed by sodium hydride promoted intramolecular ring closure of the resulting (2-aminopyridin-3-yl)(2-halopyridin-3-yl)methanone derivatives, has been developed. A similar sequence starting with (2-chloropyridin-3-yl)(3-chloropyridin-4-yl)methanone, derived from 3-chloropyridine and 2-chloropyridine-3-carbaldehyde, leads to the formation of 10-substituted pyrido[2,3-b][1,7]naphthyridin-5(10H)-ones.

■ Development of a Facile and Inexpensive Route for the Preparation of α-Halobenzopyridines from α-Unsubstituted Benzopyridines

Osamu Sugimoto,* Hyuma Iwasaki, and Ken-ichi Tanji

*Laboratory of Organic Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 552-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan

Abstract

A facile and inexpensive route for the preparation of α-halobenzopyridines from α-unsubstituted benzopyridines via N-methylbenzopyridin-α-ones was developed. α-Unsubstituted benzopyridines were converted easily into the corresponding N-methylbenzopyridin-α-ones, which were halogenated using PPh3-TCICA or PPh3-DBICA without using solvent to give α-halobenzopyridines.

■ An Efficient Synthetic Route towards Novel 3N-Substituted Thieno[2,3-d]pyrimidin-4(3H)-ones

Monaem Balti,* Maha Hachicha, and Mohamed Lotfi El Efrit

*Department of Chemistry, Faculty of Sciences of Tunis-Tunisia, El Manar-B.P. 94 Poste Romena, 1068, Tunisia

Abstract

During the last few years, condensed thienopyrimidine derivatives have received considerable attention. Herewith it has been reported the synthesis of some novel 3N-substituted thieno[2,3-d]pyrimidin-4(3H)-ones appended to different bio-potent moieties hopping to obtain new derivatives with dual biological activities.

■ CoCl2•6H2O-Promoted Pinner-Dimroth Tandem Reaction: Facile Synthesis of 3-Substituted Isoindolinones

Mingxing Liu, Jiarong Li, Qi Zhang, and Daxin Shi*

*Department of Chemical Engineering, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing Postcode: 100081, China

Abstract

A convenient one-pot synthesis of 3-substituted isoindolinones were reported in good yield via Pinner-Dimroth tandem reaction of 1,3-dicarbonyl compounds and 2-cyanobenzaldehyde in the catalysis of CoCl2•6H2O. This method has advantages of time efficiency and mild reaction conditions.