HETEROCYCLES

■ Contents

■ Total Synthesis of Gambierol

Yuji Mori*

*Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku, Nagoya 468-8503, Japan

Abstract

Gambierol is a marine polycyclic ether toxin isolated from the cultured cells of the ciguatera causative dinoflagellate Gambierdiscus toxicus. The fascinating molecular structure of gambierol, its association with ciguatera poisoning, and its potential biological activity have drawn significant attention from the synthetic community and provided a strong impetus for the development of an efficient path by which a total synthesis can be achieved. We recently accomplished the synthesis of gambierol based on an oxiranyl anion strategy. To date, four total syntheses have been reported. This review focuses on the efforts that culminated in the total synthesis of gambierol.

■ The Unexpected Formation and Structure of 4,6-Dimethylthieno[3,4-c]thiophene-1(3H)-thione

Nathan C. Tice,* Sarah M. Peak, and Sean Parkin

*Department of Chemistry, Eastern Kentucky University, Richmond, KY, 40475-3102, U.S.A.

Abstract

The reaction of 2,5-dimethylthiophene-3,4-dicarboxaldehye (1) with excess Lawesson’s Reagent afforded the unexpected 5,5-fused ring thienothione derivative, 4,6-dimethylthieno[3,4-c]thiophene-1(3H)-thione (2), in good yield (79%). The desired non-classical thiophene, 1,3-dimethylthieno[3,4-c]thiophene (3), was observed by GC/MS as a minor product (approximately 5%) along with thione 2. The thienothione 2 was characterized spectroscopically and its structure was confirmed by X-ray crystallography. The formation of compound 2 is proposed to occur through a 1,3-hydride shift.

■ An Enantio- and Diastereocontrolled Synthesis of (–)-Salinosporamide A

Yosuke Sato, Hayato Fukuda, Masaki Tomizawa, Tomohito Masaki, Masatoshi Shibuya, Naoki Kanoh, and Yoshiharu Iwabuchi*

*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan

Abstract

The enantio- and diastereocontrolled total synthesis of (–)-salinosporamide A, a potent 20S proteasome inhibitor, was accomplished through organocatalytic aldolization, diastereoselective Claisen condensation, a Rh-catalyzed Reformatsky reaction, and an AZADO-catalyzed oxidative β-lactonization reaction as the key reactions.

■ Synthesis and Antimicrobial Evaluation of Some New Pyridine Based Heterocycles

Elham S. Darwish, Nabila A. Kheder, and Ahmad M. Farag*

*Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt

Abstract

A facile and convenient synthesis of pyridine, pyridazine, 2(3H)-1,3,4-thiadiazole and pyrazole derivatives incorporating a pyridine-2-ylcarboxamido moiety via the versatile, readily accessible 3-oxo-N-(pyridin-2-yl)butanamide is described. Antimicrobial evaluation of some selected examples from the synthesized products was carried out and showed moderate activity.

■ Triacylated Anthocyanidin 3-Arabinosylglucoside-7,3’-diglucosides Isolated from the Bluish Flowers of Tradescantia virginiana Cultivars and Their Distribution in the Tradescantieae

Fumi Tatsuzawa,* Norio Saito, Kazushi Maeyama, Masato Yokoi, Atsushi Shigihara, and Toshio Honda

*Laboratoryof Olericultural and Floricultural Science, Faculty of Agriculture, Iwate University, 3-18-8 Ueda, Morioka, Iwate 020-8550, Japan

Abstract

Two triacylated anthocyanidin 3-arabinosylglucoside-7,3’-diglucosides were isolated from the purple-violet - violet-blue flowers of Tradescantia virginiana cultivars. The structures were determined to be 3-O-[6-O-(2-O-(trans-caffeoyl)-α-arabinofuranosyl)-β-glucopyranoside]-7,3’-O-di-[6-O-(trans-caffeoyl)-β-glucopyranoside]s of delphinidin and cyanidin. The former is a new anthocyanin in plants, whereas the latter, a rare anthocyanin has been recognized to be present in Zebrina pendula. Both anthocyanins exhibited typical three λmax in the visible region at 537, 574 and 620 nm for the delphinidin glycoside and at 510, 545 and 580 nm for the cyanidin glycoside in a 5.6 pH solution. These spectroscopic characteristics might be responsible for forming the intramolecular co-pigmentation between anthocyanidin and caffeic acid residues in these pigments. By HPLC analysis of nine species of the tribe Tradescantieae it was revealed that polyacylated anthocyanidin 3-arabinosylglucoside-7,3’-diglucosides were commonly found in all these plants as their major anthocyanins.

■ Synthesis of Naphtho[2,3-b]- and Naphtho[1,2-b]-fused Thieno[2,3-d][1]benzoxepins and Thieno[2,3-d][1]benzothiepins

Ivana Ozimec Landek,* Dijana Pešić, Rudolf Trojko, Maja Devčić Bogdanović, Mladen Merćep, and Milan Mesić

*IRU Chemistry, GlaxoSmithKline Research Centre Zagreb Limited, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia

Abstract

Synthesis of four novel classes of structurally related fused hetero-pentacyclic compounds, naphtho[2,3-b]thieno[2,3-d][1]benzothiepins (Ia), naphtho[1,2-b]thieno[2,3-d][1]benzothiepins (IIa), naphtho[2,3-b]thieno[2,3-d][1]benzoxepins (Ib,c) and naphtho[1,2-b]thieno[2,3-d][1]benzoxepins (IIb,c), is described. The key intermediates were the tetracyclic ketones, benzo[b]-naphtho[f]-fused thiepinones 1a,b and oxepinones 1c-f, formed by intramolecular cyclization of the corresponding 2-naphthalenylthio- (2a,b) and 2-naphthalenyloxy-substituted (2c-f) phenylacetic acid derivatives. Reaction of ketones 1a-f with Vilsmeier reagent provided β-chlorovinyl aldehydes 10a-f that readily cyclized with ethyl 2-mercaptoacetate to form thieno[2,3-d]-fused derivatives of benzo-naphtho-thiepins 11a,b and benzo-naphtho-oxepins 11c-f. Reduction of ester group of 11a-f afforded final hydroxymethyl derivatives 12a-f.

■ Rearrangement of 2-(2,5-Dioxopyrrolidin-1-yl)guanidine: An Efficient Synthesis and Structure of 3-(5-Amino-1H-1,2,4-triazol-3-yl)propanoic Acid and Derivatives

Victor M. Chernyshev,* Anna V. Chernysheva, and Zoya A. Starikova

*Department of Chemistry, South-Russia State Technical University, Prosveschenya, 132, Novocherkassk 346428, Russia

Abstract

The reaction between aminoguanidine and succinic acid in water under acid catalysis yields a mixture of guanyl- and digyanylhydrazides of succinic acid, which turns into a poorly separable mixture of 3-(5-amino-1H-1,2,4-triazol-3-yl)propanoic acid (3) and 3,3'-(ethane-1,2-diyl)bis(1H-1,2,4-triazol-5-amine) (5) in basic media. The fusion of aminoguanidine hydrochloride with succinic anhydride at 150-170 °C results in the regioselective formation of 2-(2,5-dioxopyrrolidin-1-yl)guanidine hydrochloride (11). Compound 11 upon heating in an aqueous solution in the presence of alkali quantitatively rearranges into 3-(5-amino-1H-1,2,4-triazol-3-yl)propanoic acid (3). This reaction represents a new rearrangement in the 2,5-dioxopyrrolidine series. Investigations by pKa determination, IR, NMR and X-ray revealed that compound 3 exists both in unionized and zwitterionic forms.

■ Anhydrous FePO4: A Green and Cost-Effective Catalyst for the One-Pot Three Component Synthesis of 2,4,5-Triarylated Imidazoles

Farahnaz K. Behbahani,* Talaye Yektanezhad, and Afshin R. Khorrami

*Department of Chemistry, School of Sciences, Islamic Azad University Karaj Branch, Moazen St., Karaj 31485-313, Iran

Abstract

A simple and efficient synthesis of 2,4,5-triarylated imidazoles is achieved by three-component cyclocondensation of benzil and benzoin, aryl aldehyde and ammonium acetate using FePO4 as a catalyst in refluxing ethanol. The key advantages of this process are high yields, cost effectiveness of catalyst, easy work-up, purification of products by non-chromatographic methods and developing of a new derivative of 2,4,5-triarylated imidazole.

■ Ozonolyses of Isophorone and of 3-Methyl-2-cyclohexen-1-one and Subsequent Reactions of the Respective Ozonides to Afford Di-, Tri- and Tetraozonides

In Chan Jung,* Sad Alam Sheikh, Byong-Mun Jon, Wei Li, Bon-Suk Goo, and In-Soo Jeong

*Department of Chemistry, Hanseo University, Seosan 356-706, Korea

Abstract

Ozonolyses of isophorone (1a) and 3-methyl-2-cyclohexen-1-one (1b) in pentane, followed by treatment of the ozonolyses products with O-methyl- hydroxylamine afforded the ozonides 3,3,5-Trimethyl-6,7,8-trioxabicycle[3.2.1]octane-1-carbaldehyde-O-methyloxime (5a) and 5-Methyl-6,7,8-trioxabicyclo[3.2.1]octane-1-carbaldehyde-O-methyloxime (5b), respectively. Coozonolyses of ozonides 5 with selected carbonyl compounds resulted in the formation of diozonides (9, 11), triozonides (12) and tetraozonides (14).

■ New Xanthones from the Barks of Cratoxylum sumatranum ssp. neriifolium

Warraphong Nuangnaowarat, Worrapong Phupong,* and Masahiko Isaka

*School of Science, Walailak University, Thaiburi, Thasala, Nakhon Si Thammarat 80161, Thailand

Abstract

Three new prenylated xanthones, neriifolone A-C (1-3), and eight known xanthones (4-11) were isolated from the barks of Cratoxylum sumatranum ssp. neriifolium. All the new compounds were characterized by intensive spectroscopic methods (1D and 2D NMR, UV and IR spectroscopy and mass spectrometry).

■ Substituent Effect of 7-Hydroxy-1-methylquinolinium Derivatives: A Photochemical Approach to Development of New Fluorescent pH Indicator

Naoko Senda, Atsuya Momotake, and Tatsuo Arai*

*Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki 305-0006, Japan

Abstract

Substituent effect of N-methyl-7-hydroxyquinolinium derivatives on photochemical properties in aqueous solution has been investigated. The efficiency of fluorescence emission from excited zwitter ion enhanced significantly by introduction of methyl group(s). pH Dependence of photochemical behavior of the quinolinium derivatives is also investigated.

■ Diastereoselective Reduction of Chiral N-Tosyl-2-benzoyl-1,3-oxazine Derived from (1R)-(+)-Camphor

Kwang-Youn Ko* and Hoseop Yun

*Department of Chemistry, Ajou University, 5 Wonchun-Dong, Youngtong-Gu, Suwon 443-749, Korea

Abstract

The stereochemistry of reduction of chiral N-tosyl-2-benzoyl-1,3-oxazine prepared by condensation of 1,3-amino alcohol derived from (1R)-(+)-camphor with phenylglyoxal was investigated using various reducing agents. Based on X-ray crystallography, 2-benzoyl group in 1,3-oxazine ring was situated in the axial position. High diastereoselectivity observed in the hydride reduction can be explained by a chelate model where N-tosyl oxygen atom takes part in chelation rather than ring oxygen atom.

■ Synthesis of Isochromans by Hydriodic Acid or Iodine Mediated Cyclization Reactions of 1-(2-Vinylphenyl)propan-2-ols

Kazuhiro Kobayashi,* Kazuaki Shikata, Hiroki Maegawa, Shuhei Fukamachi, Miyuki Tanmatsu, and Hisatoshi Konishi

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

Abstract

Treatment of 1-(2-vinylphenyl)propan-2-ols, which can be easily prepared from 2-bromostyrenes and epoxides, with hydriodic acid in acetonitrile yields the corresponding isochromans (1H-3,4-dihydro-2-benzopyrans). When the above alcohols are treated with iodine in acetonitrile in the presence of sodium hydrogencarbonate, the corresponding 1-iodomethylisochromans are obtained, which can be easily converted into the corresponding 1-alkyl(or aryl)sulfanylmethylisochromans on treatment with sodium thiolates in DMF.

■ An Efficient Synthesis of New Thiazole Based Heterocycles

Yahia N. Mabkhot, Nabila A. Kheder, and Ahmad M. Farag*

*Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt

Abstract

Synthesis of new aminopyrazole, pyrazolo[3,4-d]-1,2,3-triazine, 1,3,4-thiadiazole, thiophene and 1,2-dihydropyridine derivatives containing thiazole template has been carried out by simple, efficient and good yielding routes starting from the versatile and readily accessible 2-cyano-N-(thiazol-2-yl)acetamide.

■ New Prenylated Xanthone from the Branch of Garcinia costata

Warraphong Nuangnaowarat, Worrapong Phupong,* Kamolphan Intereya, and Masahiko Isaka

*School of Science, Walailak University, Thaiburi, Thasala, Nakhon Si Thammarat 80161, Thailand

Abstract

A new triprenylated xanthone, costatin (1), together with five known xanthones (2-6), was isolated from a branch of Garcinia costata (Guttiferae). The structure was elucidated on the basis of spectroscopic data. All xanthone derivatives were evaluated for antimalarial, anti-tuberculosis (TB), cytotoxicity against human breast adenocarcinoma cell line (MCF-7), anti-human KB-cell line and cytotoxicity against African green monkey kidney (Vero) cells. Costatin (1) exhibited significant antimalarial activity (IC50 1.57 μg/mL); however, it also showed comparable cytotoxic activity (IC50 1.12 μg/mL).