HETEROCYCLES

■ Contents

■ Synthetic Studies on Azacyclotribenzylenes

Kenta Hayashi, Shoko Inoue, Hanae Shimizu, Akiko Kobayashi, Miyuki Ishizaki, Yutaka Matsuoka, Kiyoshi Nishitani, and Hiroshi Hara*

*Faculty of Pharmaceutical Sciences, Science University of Tokyo, 2641 Yamazaki, Noda, Chiba 278-8510, Japan

Abstract

Azacyclotribenzylene compounds (1, 2) and several of their N-alkyl derivatives (3-6) were synthesized via biarylamines (12, 14) in good yield. Conformational studies of them are also discussed.

■ Enantioselective Synthesis of Poison-Frog Alkaloid 237D and Determination of Absolute Stereochemistry

Naoki Toyooka,* Masashi Kawasaki, Hideo Nemoto,* John W. Daly, Thomas F. Spande, and H. Martin Garraffo

*Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan

Abstract

An enantioselective synthesis of the 5-heptyl-8-methylindolizidine ((-)-7) has been achieved. Alkaloid ((-)-7, (MW 237)) was used to determine the relative and absolute stereochemistry of the natural indolizidine 237D from frog skin as 5S, 8S, 9R using GC-IR and GC-MS. Chiral gas-chromatographic comparisons with catalytically reduced (+)-235B” and (-)-235B’ indicated (-)-7 had the same absolute stereochemistry as the dihydro-product resulting from (-)-235B’ and is naturally occurring in certain extracts of Panamanian poison frogs (Dendrobates).

■ The Thorpe-Ingold Effect in Glutarimide Derivatives. Part II

Michal Pawlowski, Jan K. Maurin, Andrzej Leniewski, Krystyna Wojtasiewicz, and Zbigniew Czarnocki*

*Faculty of Chemistry, Warsaw University, Pasteura St.1, 02-093 Warsaw, Poland

Abstract

Differently substituted glutarimides, 3-methylglutarimide (12), 3,3-dimethylglutarimide (14) and 3,3,4,4-tetramethylglutarimide (18) were prepared and their reactivity towards aryllithiums was investigated. The influence of Thorpe-Ingold effect on the distribution of products in tautomeric equilibrium was observed together with a total regioselectivity of the process. For imide (12) only keto amide (13) was isolated. Imide (14) resulted in formation both hydroxy lactam (16) and keto amide (15), and imide (18) gave only hydroxy lactam (24).

■ Mild, Selective and High-Yield Oxidation of Hantzsch 1,4-Dihydropyridines with Lead(IV) Acetate

Mladen Litvic,* Ivica Cepanec, Mirela Filipan, Karmen Kos, Anamarija Bartolincic, Vinka Druskovic, Mohamed Majed Tibi, and Vladimir Vinkovic

*R & D, Belupo Pharmaceuticals & Cosmetics Inc., Radnicka c. 224, 1000 Zagreb, Croatia

Abstract

Aromatization of 1,4-dihydropyridines with lead(IV) acetate under mild reaction conditions is described. The method is very selective, mild and versatile in the synthesis of different substituted pyridines.

■ First Isolation of Both Indolylcarbinols and Diindolylalkanes from Microwave-assisted Acid (Clay)-catalysed Reaction of Indoles with Diethyl Ketomalonate

Manas Chakrabarty,* Sulakshana Karmakar, and Yoshihiro Harigaya

*Department of Chemistry, Bose Institute, 93/1, A. P. C. Road, Kolkata-700009, India

Abstract

Indoles (1a-f) react with diethyl ketomalonate on montmorillonite K10 clay under microwave irradiation to furnish expeditiously (1-4 min) the corresponding indol-3’-ylcarbinols (2a-f; 20-45%) and the respective diindolylalkanes (3a-f; 5-35%), which constitute the first direct evidence for the intermediacy of indolylcarbinols in the formation of diindolyl-alkanes from the acid-catalysed reaction of indoles with aldehydes and ketones.

■ Synthesis and Structure of New Heterocyclic Derivatives of Curcumin

M. Concepción Lozada, Raúl G. Enríquez,* Carlos E. Lobato, Benjamín Ortíz, Manuel Soriano, Dino Gnecco, and William F. Reynolds

*Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán 04510, Mexico

Abstract

New heterocyclic derivatives of curcumin (3) of different ring size were synthesized by reaction of a key intermediate, 1,7-bis(4-acetoxy-3-methoxyphenyl)hepta-3,5-dione (5) with some bi-nucleophilic molecules. These new synthetic derivatives were obtained in good yields and the structure of all compounds was supported by MS, IR, 1D and 2D ¹H and ¹³C NMR spectra and elemental analysis.

■ 3-Benzoyl-2-isopropyl-4-alkyloxazolidin-5-ones as Efficient and Inexpensive Sources of Enantiopure α,α-Dialkyl α-Amino Acids and α,β-Dialkyl α,β-Diaminopropionic Acids

Susana Rojas-Lima,* Omar Téllez-Zenteno, Heraclio López-Ruiz, Lizeth Loubet-González, and Alejandro Alvarez-Hernandez

*Chemical Research Center (CIQ), Autonomous University of Hidalog (UAEH), University City, Pachuca-Tulancingo Road Km 4.5, Pachuca de Soto, Hidalogo, CP 42076, Mexico

Abstract

It is shown that the 3-benzoyl-2-isopropyl-4-alkyloxazolidin-5-ones (12), derived from isobutyraldehyde and α-amino acids are as efficient as, but more economical than, the corresponding tert-butyl compounds (9), as sources of enantiopure α,α-dialkylated α-amino acids (e.g., 21-23). In the absence of alkylating agents, the anions of (2R,4S)-12 and its enantiomer undergo a fragmentation-recombination process to generate (1S,2’R,4’S)-N-[1-(3-benzoyl- 2-isopropyl-4-methyl-5-oxo-oxazolidin-4-yl)-2-methylpropyl]benzamide ((1S, 2’R,4’S)-20), and its enantiomer. Acidic methanolysis of these condensation products provides access to α,β-dialkylated α,β-diaminopropionic acids [e.g., (2S,3S)-2,3-bisbenzoylamino-2,4-dimethylpentanoic acid methyl ester ((2S,3S)-24)).

■ Synthesis and Cyclization Reaction of Pyrazolin-5-one Derivatives

Jae-Chul Jung, E. Blake Watkins, and Mitchell A. Avery*

*Department of Medicinal Chemistry and the Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677, U.S.A.

Abstract

A versatile synthetic method for preparing 3-pyrazolin-5-ones and 5,8-dihydro-1H-pyrazolo[1,2-a]pyridazines from simple β-keto esters is demonstrated. The synthetic strategies involve the acylation of β-keto esters, cyclocondensation with hydrazine followed by trapping with a diene under oxidative conditions.

■ New Total Synthesis of Dendroamide A from Dehydrodi- and tripeptides

Yasuchika Yonezawa, Naoki Tani, and Chung-gi Shin*

*Departmnet of Applied Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

New total synthesis of triheterocyclic cyclopeptide bistratamide-type dendroamide A, isolated from the cyanobacterium Stigonema dendroideum, was achieved by various conversions of δ¹-dehydrodi- and δ³-dehydrotripeptides.

■ Three Glucosides from Lycopodium clavatum

Motoo Tori*, Yoshie Mukai, Katsuyuki Nakashima, and Masakazu Sono

*Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihamabouji, Yamashiro-machi, Tokushima, 770-8514, Japan

Abstract

Three new glucosides were isolated as their acetates from Japanese Lycopodium clavatum and the structures of acetates were determined based on extensive 2D NMR spectra. Two of them had the apigenin moiety attached to the anomeric position of glucose. The third one had a benzoate unit at the anomeric position, a p-coumarate at the 6-position, and a ferulate at the 2-position of the glucosyl unit.

■ Electron Transfer-initiated and Highly Selective Photocyclization of N-Acyl-α-dehydroarylalaninamides to 3,4-Dihydroquinolinone Derivatives

Kei Maekawa, Kunio Fujita, Katsuyuki Iizuka, Tetsutaro Igarashi, and Tadamitsu Sakurai*

*Departmnet of Applied Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1 Rokkakubashi, Kanagawa-ku, Yokohama 221-8686, Japan

Abstract

The irradiation of (Z)-N-acyl-α-dehydroarylalaninamides [(Z)-1] in methanol containing 1,8-diazabicyclo[5.4.0]undec-7-ene gave substituted 3,4-dihydro-2-quinolinones (2) in high yields along with minor amounts of 2-quinolinone (3) and 4,5-dihydrooxazole (4) derivatives. Analysis of substituent and tertiary amine base effects on the selectivity of each product showed that 2 and 4 are formed via electron transfer from the amine to the excited-state (E)-1, the cyclization of which proceeds in competition with this electron transfer to afford 3.

■ Chemoselective Multicomponent Condensation of 1,3-Cyclohexanedione, Urea or Thiourea with Aldehydes: One-Pot Synthesis of Two Families of Fused Heterobicyclic and Spiro-fused Heterobicyclic Aliphatic Rings

Yulin Zhu, Yuanjiang Pan,* and Shenlin Huang

*Department of Chemistry, Zhejiang University (YuQuan Campus), Hangzhou, 310027, China

Abstract

One-pot chemoselective condensation of 1,3-cyclohexanedione, urea or thiourea with aldehydes has been performed by using TMSCl as a Lewis acid in DMF/MeCN. This extended Biginelli-type reaction afforded two families of fused heterobicyclic and spiro-fused heterobicyclic compounds in excellent yields. para-Substituted benzaldehydes exhibited different chemical behaviors to ortho- or meta-substituted benzaldehydes and aliphatic aldehydes. The possible mechanism was discussed to account for experimental results.

■ One-Pot Synthesis of Alkyl Indeno[1,2-b]quinoxalin-11-ylideneacetates under Solvent-free Conditions

Javad Azizian,* Mohammad R. Mohammadizadeh, Narges Karimi, Ali A. Mohammadi, and Ali R. Karimi

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

Abstract

A series of alkyl indeno[1,2-b]quinoxalin-11-ylideneacetates (3a-f) were prepared using the simple one-pot reactions involving triphenylphosphine, alkyl bromoacetate, ninhydrin, 1,2-phenylenediamines and NaOAc under solvent free-condition.

■ Stereoselective Gram-Scale Synthesis of (S)-5,5-Dimethyl-4-phenyloxazolidin-2-one

Shigeo Sugiyama,* Satoshi Arai, and Keitaro Ishii*

*Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

A stereoselective gram-scale synthesis of (S)-5,5-dimethyl-4-phenyloxazolidin-2-one, SuperQuat [(S)-1], is described. The key step is the diastereoselective reduction of (E)-imine (2), which is synthesized from 2-hydroxy-2-methylpropiophenone (4) and (S)-α-methylbenzylamine using sodium borohydride and acetic acid to give (1S,αS)-2-methyl-1-(α-methyl- benzyl)amino-1-phenylpropan-2-ol (5).

■ A New Phloroglucinol Dimer from Mallotus pallidus

Kittisak Likhitwitayawuid* and Butsarakham Supudompol

*Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand

Abstract

A phytochemical investigation of an EtOAc extract of the leaves of Mallotus pallidus led to the isolation of a new phloroglucinol dimer, mallopallidusol (1), along with five known compounds.

■ Preparation of New Vindoline Derivatives by Palladium-catalyzed Cross-Coupling Reaction

Melinda Fekete, Pal Kolonits, and Lajos Novak*

*Institute for Organic Chemistry, Budapest University of Technology and Economics, H-1111 Budapest, Gellert ter 4, Hungary

Abstract

A new series of aryl-substituted vindoline derivatives (3) was prepared by palladium-catalyzed cross-coupling reaction of 15-iodovindoline (1c) with arylboronic acids (2).

■ Stilbenoids from Leaves of Upuna borneensis

Tetsuro Ito,* Ibrahim Iliya, Toshiyuki Tanaka, Ken-ichi Nakaya, Yukihiro Akao, Yoshinori Nozawa, Jin Murata, Dedy Darnaedi, and Munekazu Iinuma

*Gifu Prefectrual Institute of Health and Environmental Sciences

Abstract

An acetone extract of the leaves of Upuna borneensis afforded two stilbene tetramer derivatives (upunaphenols F and G) together with four stilbenoids (vaticanols B and C, piceid and cis-piceid). The structures and their relative stereochemistry were determined by spectroscopic techniques, in particular by using 2D NMR method. Upunaphenol G was found to suppress cell growth in HL60 cells with IC₅₀ at 15.6 μM.

■ An Improved Method for Chlorination of Nitrogen-containing π-Deficient Heteroaromatics Using Triphenylphosphine and Trichloroisocyanuric Acid

Osamu Sugimoto* and Ken-ichi Tanji*

*Laboratory of Organic Chemistry, School of Food and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan

Abstract

Phosphorus compound prepared by reaction of triphenylphosphine with trichloroisocyanuric acid was found to be applied to chlorination of nitrogen-containing π-deficient heteroaromatics. As self-decomposition of the chlorinating reagent hardly proceeds, the reagent is more useful than phosphorus compound prepared by triphenylphosphine and N-chlorosuccinimide.

■ A Facile Synthesis of Asymmetrical 2,3-Dicyano-substituted Tetrathiafulvalene Derivatives

Tie Chen, Chunlan Wang, Zhiqi Cong, Bingzhu Yin,* and Kimiaki Imafuku*

*Department of Chemistry, Faculty of Science, Kumamoto University, Kurokami 2-39-1, Kumamoto 860-8555, Japan

Abstract

The cross-coupling reactions of 4,5-dicyano-1,3-dithiol-2-one (3) and 4,5-bis(alkylthio)- and 4,5-bis(methoxycarbonyl)-1,3-dithiole-2-thiones (4a-e) gave asymmetrical 2,3-dicyanotetrathiafulvalenes (5a-e) having electron-donating or electron-withdrawing substituents at the 6,7-positions under high dilution condition. A pyrrole-fused tetrathiafulvalene (5f) was also obtained. Their electrochemical behaviors were measured by means of cyclic voltammetry.

■ Survey of Briarane-related Diterpenoids — Part II

Ping-Jyun Sung,* Pi-Chen Chang, Lee-Shing Fang, Jyh-Horng Sheu, Wei-Chen Chen, Yu-Pei Chen, and Mei-Ru Lin

*National Museum of Marine Biology and Aquarium, 2 Houwan Road, Checheng, Pingtung, Taiwan 944, Taiwan, R.O.C.

Abstract

The structures, names, biological activity, and references of sixty-six new briarane-related diterpenoids are described in this mini-review. All briaranes are obtained from Gorgonacea (genus Briareum, Erythropodium, Ellisella, and Junceella) and Pennatulacea (genus Cavernularia and Pteroeides). Some of these natural products showed potential biological activity.