HETEROCYCLES

■ Contents

■ 4-Hydroxy-6-methyl-2-pyrone: A Versatile Synthon in the Synthesis of Heterocyclic Scaffolds via Multicomponent Reactions

Ghodsi Mohammadi Ziarani,* Razieh Moradi, Marziyeh Zandiyeh, and Negar Lashgari*

*Department of Chemistry, Alzahra University, Tehran, Iran

Abstract

4-Hydroxy-6-methyl-2-pyrone has been utilized in the synthesis of various heterocyclic compounds. It is a potential 1,3-dicarbonyl compound with diverse synthetic applications that have been extensively investigated. There is a wide range of multicomponent reactions that include 4-hydroxy-6-methyl-2-pyrone in the synthesis of heterocyclic compounds. This review highlights the advances in the use of this compound as starting material in the synthesis of various organic compounds.

■ Novel One-Pot Synthesis of Dihydroacenaphtho[1,2-f][1,3]oxazepines via 1,4-Dipolar Cycloaddition Reaction

Mervat S. Sammor, Mustafa M. El-Abadelah,* Ahmad Q. Hussein, and Firas F. Awwadi

*Department of Chemistry, Faculty of Science, The University of Jordan, Amman 11942, Jordan

Abstract

A facile three-component reaction involving 3-alkyl(aryl)imidazo[1,5-a]pyridines 7a-g, dimethyl acetylenedicarboxylate 2 (DMAD) and acenaphthene-1,2-dione 5 led to the construction of the respective dihydroacenaphtho[1,2-f][1,3]oxazepinedicarboxylates 10a-g in fair yields. Structures of the latter tetracyclic adducts, are based on NMR and MS spectral data and confirmed by single-crystal X-ray diffraction analysis for compound 10a. Most logically, the reaction proceeds via initial formation of the relevant diastereomeric spiro[1,3]oxazine-1,4-dipolar cycloadducts 12, 13 which then suffer skeletal rearrangement leading to the respective acenaphtho[1,2-f]-[1,3]oxazepines 10a-g.

■ A Short-Step Synthesis of Onychine and the Related 4-Azafluorenones via Hetero Diels-Alder Reaction of 5-Substituted Isotellurazoles

Yusuke Taneichi, Kazuaki Shimada,* and Toshinobu Korenaga

*Department of Chemistry and Biosciences, Faculty of Science and Engineering, Iwate University, Iwate 020-8551, Japan

Abstract

Synthesis of onychine and the related 4-azafluorenones was achieved from 5-substituted isotellurazoles through a two-step procedure involving hetero Diels-Alder reaction with methyl phenylpropiolate and the subsequent Friedel-Crafts ring closure of the resulting pyridine derivatives.

■ Prins Reaction Using Trioxane for Trisubstituted, cis-Fused Hexahydro-2H-furo[3,2-b]pyran Derivative

Oriel Hlokoane, Hiyori Itagaki, Manami Chiba, Taiki Noda, Yuichi Takasaki, Kei Miyako, Ryuichi Sakai, Yuichi Ishikawa,* and Masato Oikawa*

*Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan

Abstract

The construction of cis-fused heterobicyclic system involved in neuroactive natural products such as dysiherbaine has been accomplished by employing Prins strategy using 1,3,5–trioxane as an equivalent for formaldehyde. The reactions allowed stereoselective construction of the trisubstituted cis-fused hexahydro-2H-furo[3,2-b]pyran with maximum yield of 60%.

■ Synthesis of the Anti-Prostate Cancer Drug Abiraterone Acetate

Siyue Ma, Jianheng Li,* Huayang Tang, and Feng Xu

*School of Pharmacy, Hebei University, No.180 WuSi Road, Baoding, 071002, China

Abstract

Abiraterone acetate is used for the treatment of castration-resistant prostate cancer. Abiraterone acetate was synthesized from dehydroepiandrosterone via a three-step reaction including the formation of tosylhydrazone, cross-coupling reaction and acetylation, and a two-step purification including column chromatography and recrystallization with an overall yield of 51.9%. Here, an improved procedure for the preparation of abiraterone acetate is described. This synthetic process is of easy operation and low cost, which is suitable for industrialization.

■ Synthetic Studies of Yessotoxin: Stereoselective Annulation of the CD and JK Ring Fragments by Using Pd(II)-Catalyzed Cyclization

Hajime Yokoyama,* Genki Moriyama, Kazuki Nishida, Yasuhiro Kusumoto, Kiyoshi Tsuge, Masahiro Miyazawa, and Yoshiro Hirai

*Department of Chemistry, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan

Abstract

Yessotoxin is the polycyclic ether implicated in diarrheic shellfish poisoning. This toxin has A-K ring system involving 6-, 7-, 8-membered ether rings. We have been studying high stereoselective Pd(II)-catalyzed cyclization. Herein we describe the CD and JK ring fragments of yessotoxin by our annulation based on Pd(II)-catalyzed cyclization. The efforts to understand these high stereoselectivities are also disclosed. This annulation method could be applicable to other polyethers and related natural products.

■ A Practical Synthesis of the Cyclic Butylene Terephthalate Trimer

Xiaolin Li, Pu Zhou, Wenxuan Wu, Li Zhan, Ting Liu, Fan Yang, Jie Tang, Shanbao Yu, Hui Li, and Yu Luo*

*Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, China

Abstract

This paper described a practical synthetic approach for the cyclic butylene terephthalate trimer (7). The key step was a ring-closing metathesis, using Grubbs’ second-generation catalyst to form the macrocyclic ring. The advantages of this procedure included short reaction steps, simple operations and good yields.

■ Nazarov Cyclization of an Indolyl Vinyl Ketone Promoted by Acetyl Chloride and Sodium Iodide: Formal Synthesis of Bruceolline E

Takumi Abe*

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

Abstract

An acetyl chloride/NaI-mediated Nazarov-type cyclization of an indolyl vinyl ketone was developed to give a cyclopenta[b]indole in high yield. An acyl Finkelstein reaction is a key feature for this unprecedented Nazarov-type cyclization.

■ Brønsted Acid-Promoted Multicomponent Reaction for the Construction of Pyrrolocoumarin Derivatives

Zhiwei Chen,* Sunjia Ye, and Xiongfei Zhang

*Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China

Abstract

An efficient one-pot synthesis of functionalized indole-containing pyrrolocoumarin derivatives via a three-component reaction of 4-aminocoumarins, arylglyoxal monohydrates and indoles promoted by p-TSA in ethanol is described. The attractive features of this protocol are simple starting materials, operational simplicity, short reaction time and moderate to good yields.

■ A Simple Method for Synthesis of Thioamides and Application in Synthesis of 1,2,4-Thiadiazoles

XianTing Cao, HuiYong Yang, Hui Zheng, and PengFei Zhang*

*College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China

Abstract

A novel, simple protocol is disclosed for the synthesis of 1,2,4-thiadiazoles starting from thioamides with Na2-eosin Y-sensitized titanium dioxide as catalyst through visible light irradiation (7 W blue LED light) and only 0.3 mol% catalysts were used. The raw material thioamides is prepared by aryl nitriles and sodium sulfide (Na2S·9H2O) in DMF and in this reaction, readily available, inexpensive inorganic salt (Na2S·9H2O) serves as the sulfur source and various functional groups of aryl nitriles were well and thioamides were synthesized successfully in gram-scale.

■ A Facile Ultrasound Assisted for an Efficient Synthesis of Imidazo[1,2-a]pyrazine-fused β-Carbolines

Yi-Xin Tang, Jiao Xu,* Wei Ma, Dao-Lin Wang,* and Liang Yan

*College of Chemistry and Chemical Engineering, Bohai University, Jinzhou, China

Abstract

An efficient tandem process for the synthesis of imidazo[1,2-a]pyrazine-fused β-carbolines is described. The construction of these compounds was achieved by three component reaction of 1H-indole-3-carbaldehyde, 2-aminopyrazine and trimethylsilyl cyanide via Groebke-Blackburn-Bienaymé reaction, followed by cyclization through the Pictet-Spengler reaction of the resulting 3-aminoimidazo[1,2-a]pyrazine which allowed access to the title heterocycles under ultrasound irradiation.