HETEROCYCLES

■ Contents

■ The First Chemical Synthesis of 6-Thio-D-fructopyranose via Methyl 6-Bromo-6-deoxy-1,3-O-isopropylidene-α-D-fructofuranoside as a Key Intermediate

Tadashi Hanaya,* Nobuaki Sato, and Hiroshi Yamamoto

*Department of Chemistry, Faculty of Science, Okayama University, Tsushima-naka, Okayama 700-8530, Japan.

Abstract

Selective bromination of sucrose, followed by acetalation with 2,2-dimethoxypropane in 1,4-dioxane in the presence of p-toluenesulfonic acid, afforded methyl 6-bromo-6-deoxy-1,3-O-isopropylidene-α-D-fructofuranoside (4). The first chemical synthesis of 6-thio-D-fructopyranose was accomplished from 4 through its 6-S-acetyl-6-thio derivative.

■ Direct Involvement of Benzoxazinoids in the Growth Suppression Induced by Phototropic Stimulation in Maize Coleoptiles

Riffat Jabeen, Kosumi Yamada,* Tsuyoshi Hasegawa, Eiichi Minami, Hideyuki Shigemori, and Koji Hasegawa

*Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305, Japan

Abstract

The process of growth suppression observed in the illuminated sides in response to phototropic stimulation was investigated in maize coleoptiles. In our previous studies, the increased level of benzoxazinoids,2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and 6-methoxybenzoxazolinone (MBOA), and the up-regulation of β-glucosidase (DIMBOA-glucosidase) activity have been observed in the illuminated halves. In this report, significant accumulation of hydrogen peroxide (H₂O₂) was observed in the phototropically stimulated sides. Moreover, exogenously applied DIMBOA and MBOA induced a significant up-regulation of H₂O₂ in the applied sides, respectively. In addition, lignin level was also slightly increased in the illuminated sides within 60 min. These results suggest that phototropic stimulation induced the production of benzoxazinoids, resulting to the up-regulation of H₂O₂ in the illuminated halves. Consequently, the up-regulated H₂O₂ promoted the cell-wall stiffness, leading to the growth suppression in the illuminated sides. This is the first indication that blue-light induced benzoxazinoids play the role of directional effecter in the growth suppression in the illuminated sides in maize coleoptiles.

■ Diastereoselective Synthesis of Spiro-β-lactams via Staudinger Reaction

Susana Rojas-Lima,* Lidia Santillán-Sid, Heraclio López-Ruiz, and Alejandro Álvarez-Hernández

*Chemical Research Center (CIQ), Autonomous University of Hidalgo (UAEH) University City, Pachuca-Tulancingo road Km 4.5, Pachuca de Soto, Hidalgo, CP 42076, México

Abstract

In this work, eleven new spiro-β-lactams have been prepared using the Staudinger reaction of isomaleimides (1a-d) and carboxylic acids (chloroacetic acid, (-)-menthoxyacetic acid (7) and an oxazolidinone derived acid (10)) in the presence of triphosgene under mild condition. All reactions have been shown to be stereoselective. The new stereogenic centers were assigned by X-ray diffraction.

■ A Simple and Environmentally Benign Method for the Synthesis of Naphthoxazin-3-one Derivatives

Minoo Dabiri, Akram Sadat Delbari, and Ayoob Bazgir*

*Department of Chemistry, Faculty of Science, Shahid Beheshti University, Evin, P.O. Box 19396-4716, Tehran 1983963113, Iran

Abstract

Carbamatoalkylnaphthol derivatives have been synthesized in good yields in a one-pot, and efficient process by condensation of β-naphtol, aromatic aldehydes and methyl carbamate in ionic liquid media. Ring closure of carbamatoalkylnaphthol derivatives occurred in ionic liquid media at 160 °C to give 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazin-3-one derivatives.

■ Synthesis and Aggregation of Tetrathiafulvalene-Annulated Porphyrazines

Tie Chen, Chunlan Wang, Han Qui, Longyi Jin, Bingzhu Yin,* and Kimiaki Imafuku*

*Key Laboratory of Organism Functional Factor of Changbai Mountain, Ministry of Education, 977, Park Road, Yanji City, Jilin Prov. 133002, China

Abstract

Magnesium(II)-porphyrazine (4) was prepared via a Mg-butoxide templated macrocyclization of 2,3-dicyano-6,7-dibutylthiotetrathiafulvalene in buthanol, and then 4 was converted to metal-free porphyrazine (5) by treatment with trifluoroacetic acid in the dark. 5 reacted with excess zinc acetate to give zinc(II)-porphyrazine (6) in the chlorobenzene. Their structure has been characterized by ¹H NMR, MALDI-TOF-MASS, UV-VIS, ESR and EA, and self-assembly behavior of 4 was studied with the help of TEM and DLS data. 4 self-assembled to spherical aggregates in toluene.

■ Wittig-Horner-Emmons Reactions of Triethyl 3-Methylphosphonocrotonate with 3-Formylchromones En Route to Benzophenone-Based Retinoid Candidates

Weilin Sun, Shyam Desai, Huri Piao, Patrick Carroll, and Daniel J. Canney*

*Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA

Abstract

Wittig-Horner-Emmons (WHE) reaction conditions were used in conjunction with other reactions to prepare benzophenone-based retinoid candidates. The chromone nucleus was reacted with triethyl 3-methyl-phosphonocrotonate to afford benzophenones following a known rearrangement of a reaction intermediate. Confirmations of the structure of rearranged products are provided in the form of the X-ray crystal structures and speculation regarding the mechanism for the rearrangements is included. The method provides a facile route to substituted benzophenone-based candidate ligands for retinoic acid receptors (RARs) or for a wide variety of other applications.

■ A Convenient K₂CO₃ Catalysed Regioselective Synthesis for Benzopyrano[4,3-c]pyrazoles in Aqueous Medium

Mazaahir Kidwai,* Priya, Kavita Singhal, and Shweta Rastogi

*Green Chemistry Research Laboratory, Department of Chemistry, University of Delhi, Delhi-110007, India

Abstract

This synthetic approach features heterocondensation reaction between in situ generated 3-arylidene-2,4-chromanediones and N-substituted hydrazine moiety avoiding the use of organic solvents at any stage. Water as solvent is taken for the synthesis of selective benzopyranopyrazole derivatives under microwaves (MWs). Hydroxy coumarin moiety is employed for this ecofriendly strategy.

■ Structures of Dammarane-Type Triterpene Triglycosides from the Flower Buds of Panax ginseng

Seikou Nakamura, Sachiko Sugimoto, Hisashi Matsuda, and Masayuki Yoshikawa*

*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan

Abstract

New dammarane-type triterpene triglycosides, floralginsenosides G, H, I, J, K, La, and Lb, were isolated from the flower buds of Panax ginseng C. A. MEYER together with ten known dammarane-type triterpene oligoglycosides. The structures of new compounds were elucidated on the basis of chemical and physicochemical evidence.

■ Solvation Effects on Imidazolium Salts That Contain Alkyl Side Chains

Allan D. Headley,* S. R. S. Saibabu Kotti, and Bukuo Ni

*Department of Chemistry, Texas A & M University-Commerce1, Commerece, TX 57429, U.S.A.

Abstract

Solvation effects of imidazolium salts that contain alkyl side chains in the 1 and 3 positions have been analyzed using multi-linear regression equations. The major contribution for the solvation of these compounds comes from the solvents’ hydrogen bond acceptor basicity contribution, in which there is an interaction between the solvent and H2 hydrogen of the imidazolium cation. Another solvation effect, which is minimal, comes from the solvents’ hydrogen bond donor acidity contribution, which serves to solvate the anions. The nature of the anion plays a role in the solvation of the anions. Salts with hard anions are solvated to a lesser extent via the solvents’ hydrogen bond acceptor basicity; whereas, salts with softer anions are solvated to a larger extent via this mode. There is not much discrimination in the solvation of imidazolium salts that contain the same anion and different alkyl groups in positions 1 and 3.

■ A Total Synthesis of (17S)-Hexahydro-TMC-69

Kazutoshi Sugawara,* Yasuhiro Imanishi, and Tomiki Hashiyama

*Medicinal Chemistry Research Laboratories, Tanabe Seiyaku Co., Ltd. 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan E-mail: k-suga@tanabe.co.jp

Abstract

The cdc25A protein phosphatase inhibitor (7R,8R,10R,17S)-hexahydro-TMC-69 (1a) has been synthesized in a stereoselective manner, starting from an enantiomerically pure pyranone (3) using Knoevenagel condensation as a key step.

■ Isolation and Structure Elucidation of a Potent Growth Inhibitor, Helian, from Blue Light-Illuminated Sunflower (Helianthus annuus) Hypocotyls

Tsuyoshi Hasegawa, Shigenori Togo, Yosuke Hisamatsu, Kosumi Yamada,* Kiyotake Suenaga, Mitsuhiro Sekiguchi, Hideyuki Shigemori, and Koji Hasegawa

*Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan

Abstract

A potent growth inhibitor was isolated from blue light-illuminated sunflower (Helianthus annuus) hypocotyls and identified as 8-(β-D-glucopyranosyloxy)-3-hydroxy-1,9,14-pentadecatriene-4,6-diyne (1, designated “helian”) from analysis of its ¹H and ¹³C NMR spectra, and HRFABMS. Helian 1 showed plant growth-inhibitory activity at concentrations higher than 2.6 x 10^-6 mol/L for the cress root growth test. The amount of helian was higher in the illuminated halves than in the shaded ones in phototropically stimulated sunflower hypocotyls. These results suggest that this new potent growth inhibitor, helian, may play an important role on phototropism of sunflower hypocotyls.

■ A New One-Step Synthesis of 1,2,4-Triazino[2,3-c]quinazolines

Oleksandr V. Karpenko,* Sergiy I. Kovalenko, Oleksiy O. Chekotylo, and Svitlana V. Shishkina

*Department of Pharmaceutical Chemistry, Zaporizhzhia State Medical University, prosp. Mayakovskogo 26, Zaporizhzhia, 69035, Ukraine

Abstract

A new and efficient one-step protocol for the synthesis of 3-substituted 2H-1,2,4-triazino[2,3-c]quinazolin-2-ones (5) was developed starting from 4-hydrazinoquinazoline (1) and α-ketocarboxylic acids and their esters. Corresponding hydrazones (2a,c and 3a,c,e) were isolated as intermediate products. Further cyclocondensation followed by acid-catalyzed Dimroth rearrangement resulted in the title derivatives 5.

■ Total Synthesis of (S)-(+)- and (R)-(-)-Curcudiols Based on 1,2-Aryl Migration via Phenonium Ion

Takeru Ehara, Hirofumi Yokoyama, Machiko Ono, and Hiroyuki Akita*

*School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

Total synthesis of (S)-(+)- and (R)-(-)-curcudiols (2) was achieved based on the 1,2-aryl migration of the (4R,5R)- and (4S,5S)-4-aryl-5-tosyloxy-(2E)-hexenoates (9) derived from (4R,5R)- and (4S,5S)-4-epoxy-(2E)-hexenoates (3), respectively.

■ Chemoselective Synthesis of New Dibenzo[d,f]-1,3-dioxepines and 12H-Dibenzo[d,g]-1,3-dioxocines

Graziella Tocco,* Michela Begala, Gabriele Meli, and Gianni Podda

*Farmaco Chimico Tecnologico Department - University of Cagliari, Ospedale Street n°72, 09124 - Cagliari, Italy

Abstract

A new series of dibenzodioxepine and dibenzodioxocine derivatives was prepared starting from aliphatic and aromatic aldehydes, underlining the chemoselectivity of both the catalyst and the biphenol, also confirming the importance of the hydrogen atom in αposition to the carbonyl group.

■ Synthesis and Cytostatic Evaluation of Pyridopyrimidobenzimidazole Derivatives

Kristina Starcevic, Marijeta Kralj, Katja Ester, and Grace Karminski-Zamola*

*Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, Marulicev trg 20, HR-10000 Zagreb, Croatia

Abstract

A set of novel 2,5-substituted benzimidazoles (1-7) and their cyclic derivatives (8-11) were synthesized and evaluated for their potential cytostatic effect on various tumor cell lines. The structures of the synthesized compounds were proved by means of IR, ¹H NMR and MS spectral data. Based on presented in vitro screening results we may conclude that cyclic compounds bearing nitro and amino substituents (10 and 11) showed the most pronounced growth inhibitory.

■ Synthesis of 2-Unsubstituted 2,3,5,6,7,8-Hexahydropyrazolo[4,3-d][1,2]diazepinone-8-carboxylates

David Bevk, Jurij Svete,* and Branko Stanovnik*

*Department of Organic Chemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva 5, P.O. Box 537, 1000 Ljubljana, Slovenia

Abstract

Substituted 2,3,5,6,7,8-hexahydropyrazolo[4,3-d][1,2]diazepine-8-carboxy-lates were prepared in good to excellent yields from ethyl (2E)-3-(dimethylamino)-2-{(4Z)-4-[(dimethylamino)-methylidene]-4,5-dihydro-5-oxo-1H-pyrazol-3-yl}propenoate with 1,2-disubstituted hydrazines by heating in an alcohol.

■ Synthesis of a 9-Aza Analogue of Eleutherol

Norman O. Townsend and Yvette A. Jackson*

*Department of Chemistry, University of the West Indies, Mona, Kingston 7, Jamaica, West Indies

Abstract

A 9-aza analogue of the natural product eleutherol was synthesized by intramolecular acylation of a dihydrokynurenic acid.

■ Silica Sulfuric Acid as an Efficient and Reusable Catalyst for the Pechmann Synthesis of Coumarins under Solvent-Free Conditions

Minoo Dabiri,* Peyman Salehi,* Mohammad Ali Zolfigol, and Mostafa Baghbanzadeh

*Department of Chemistry, Faculty of Science, Shahid Beheshti University, Postal Code 1983963113, Evin, Tehran, Iran

Abstract

Silica sulfuric acid is used as an efficient catalyst in the Pechmann condensation of phenols with β-keto-esters leading to the formation of coumarin derivatives in excellent yields under solvent-free conditions. It was found that the catalyst could be recycled and reused for several runs.

■ Oxidative Aromatization of 3,5-Disubstituted Isoxazolines to the Corresponding Isoxazoles with N,N,N’,N’-Tetrabromobenzene-1,3-disolfonamide (TBBDS) and 1,3-Dibromo-5,5-dimetylhydantoin (DBH) as Efficient Reagents under Mild Reaction Conditions

Davood Azarifar,* Behrooz Maleki, and Kobra Mohammadi

*Chemistry Department, School of Science, Bu-Ali Sina University, Postal Code 65174, Hamadan, Iran

Abstract

The oxidation of 3,5-disubstituted isoxazolines to the corresponding isoxazoles has been carried out using N,N,N’,N’-tetrabromobenzene-1,3-disolphonamide and 1,3-dibromo-5,5-dimethylhydantoin (DBH) as effective oxidizing agents under mild conditions at room temperature with good yields.

■ Synthesis of 4,5-Diaminopyrrolo[1,2-a]quinoline Derivatives by a Lewis Acid Catalyzed Reaction of 2-(Pyrrol-1-yl)benzaldimines with Isocyanides

Kazuhiro Kobayashi,* Yasutoshi Himei, Yuichi Izumi, Shuhei Fukamachi, Osamu Morikawa, and Hisatoshi Konishi

*Department of Materials Science, Faculty of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

N-Alkyl(or aryl)-2-(pyrrol-1-yl)benzaldimines, derived from 2-(pyrrol-1-yl)benzaldehydes and primary amines, were treated with aromatic and aliphatic isocyanides in the presence of a catalytic amount of boron trifluoride diethyl etherate to afford the corresponding 4,5-diaminopyrrolo[1,2-a]quinoline derivatives in generally fair to good yields.

■ Synthesis of 3-(2-Pyridyl)-2-pyrazoline Derivatives as Candidates for Heterocyclic Chiral Ligands of the Chirality Relay Types

Hiroshi Yanagita and Shuji Kanemasa*

*Institute for Materials Chemistry and Engineering, Kyushu University, 6-1 Kasugakoen, Kasuga 816-8580, Japan

Abstract

The synthetic work of 3-(2-pyridyl)-2-pyrazolines bearing a chiral center at the 5-position is presented. Three synthetic routes have been examined, including (1) intramolecular cyclization of the hydrazones of α,β-unsaturated ketones, (2) synthesis of N-unsubstituted pyrazolines followed by the optical resolution of diastereomers of sulfonamide derivatives, and (3) asymmetric pyrazoline synthesis between enones and arylhydrazines catalyzed by a chiral metal acetate complex catalyst.