HETEROCYCLES

■ Contents

■ Mini Review on Pyrido[2,3-c]coumarins Backbone of Santiagonamine Antibiotics

Prasanta Patra* and Susanta Patra

*Chemisty, Jhargram Raj College, West Bengal, Jhargram College Rd, Jhargram, West Bengal, India

Abstract

Santiagonamine is a natural coumarin fused pyridine, specifically pyrido[2,3-c]coumarin derivative having wound-healing activities and is extracted from stems and branches of the South American shrub Berberis darwinii Hook. It was isolated by Shamma et al. in 1984. Both coumarin and pyridine represent an important class of a multi tasking and multi functional scaffolds in organic synthesis. So, the syntheses of coumarin fused pyridine derivatives have an immense impact in the field of organic and pharmaceutical chemistry due to various biological activities displayed by such classes of compounds as well as for their natural occurrences. The main purpose of this review is to focus on different synthetic methodologies for the synthesis of specifically pyrido[2,3-c]coumarins as it is the backbone of santiagonamine antibiotics. Several methods for the synthesis of pyrido[2,3-c]coumarins have been described in the literature, most of which use 3-aminocoumarin as the starting material.

■ On the Reactivity of 2-Methylene-3-quinuclidinone in Water

Rune Ringom, Tim Blizzard, Corine Sandström, Per H. Svensson, and Lars Hagberg*

*Department of Chemistry, Aprea Therapeutics, Hälsovägen 16, Sweden

Abstract

The biologically active Michael acceptor 2-methylene-3-quinuclidinone (MQ) has a unique chemical reactivity and forms several products upon dissolution in water. With the use of X-ray, NMR and LCMS data the structures of two previously incorrectly characterised compounds are rectified. A complex equilibrium in water, containing novel dimeric species of MQ, and its dependence on temperature, pH and concentration is presented.

■ Supramolecular Self-Assembly Based on Symmetric Tetramethyl-Substituted Cucurbit[6]uril and Small Aromatic Amines

Lin Zhang, Jun Zheng, Xuanxun Wang, Zhu Tao, and Qianjun Zhang*

*Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Institute of Applied Chemistry, Guizhou University, Guiyang, 550025, China

Abstract

In this paper, the interactions formed between symmetric tetramethyl-substituted cucurbit[6]uril (TMeQ[6]) and 4-cyanoaniline (CYA), 4,4'-methylenedianiline (MET), and 4-benzylaniline (BEN), were investigated using 1H NMR spectroscopy and X-ray single crystal diffraction analysis. X-Ray single crystal diffraction showed that CYA was encapsulated in the cavity of TMeQ[6] and formed 1:1 host-guest complex 1. Both MET and BEN were located at the TMeQ[6] portal and coordinated to form complex 2 and complex 3, respectively, forming weak interactions with TMeQ[6], such as hydrogen bonding, C-H···π interactions, and ion-dipole interactions. Complexes 1~3 self-assemble to construct supramolecular nanoscale structures under the induction of [ZnCl4]2- ions. The 1H NMR spectroscopic analysis supported the crystallographic results in which an clathration or portal interaction occured between host and guest molecules.

■ Silver(I) Complexes Bearing Amine-Functionalized N-Heterocyclic Carbenes: Synthesis, Antimicrobial and Theoretical Studies

Beyhan Yiğit, Hasan Akdan, Muhittin Önderci, Selami Günal, Tuğba Taskin-Tok, Murat Yiğit,* and İsmail Özdemir

*Department of Chemistry, Faculty of Science and Art, Adıyaman University, 02040 Adıyaman, Turkey

Abstract

In this study, a series of amine functionalized benzimidazolium salts and their silver(I) N-heterocyclic carbene complexes were synthesized and characterized by FT-IR, 1H NMR and 13C NMR spectroscopy and mass spectrometry. All the compounds were evaluated for their antibacterial and antifungal activities. They showed antibacterial activity with MIC values in the range of 12.5-50 µg/mL and and antifungal activity with MIC values in the range of 25-100 µg/mL. Notably, compounds 3d and 3e exerted antibacterial activity against all tested gram negative and gram positive bacteria including Staphylococcus aureus MRSA strain with a quite low MIC value of 12.5 µg/mL. Besides these, computational study was applied to understand the biochemical activity analyzes of Ag complexes 3a-e. The findings suggest that there are components 3a and 3b with potential drug properties for future advance researches.

■ Effect of Sulfur-Containing Side Chains on Transnitrosation of N-Nitroso Compounds of Thiazolidines

Noriko Usui, Masataka Mochizuki, and Keiko Inami*

*Division of Pharmaceutical Organic Chemistry, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Daigakudo-ri 1-1-1, Sanyo-onoda-shi,Yamaguchi, Japan

Abstract

S-Nitrosoglutathione (GSNO) acts as a potential nitric oxide donor in vivo. 3-Nitroso-1,3-thiazolidine-4-thiocarboxamide (1) exhibited a high GSNO- formation activity. In this study, we synthesized novel compounds in which mercaptomethyl (2) or methylthiomethyl (3) group was incorporated into the thiazolidine skeleton instead of a thioamide group. Pseudo-first-order rate constants for GSNO formation for the reaction between the compounds and glutathione followed the order 1>>2≒3. Introduction of another substituent containing a sulfur atom into the thioamide group this time resulted in a decrease in transnitrosation activity. These differences in activity suggested that compounds 2 and 3 transnitrate via a different reaction pathway than 1.

■ Sialidase Inhibitory Activity of Synthesized Biflavonoid Glycoconjugates

Hiroaki Sasaki,* Takayuki Nagai, Takayuki Nakamura, Yusuke Umezawa, Kazuhiko Miki, Haruki Yamada, Kiyotaka Koyama, Kunio Takahashi, and Kaoru Kinoshita

*Department of Pharmacognosy and Phytochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

Ginkgetin (1) and sciadopitysin (2) have been shown to exhibit influenza virus sialidase inhibitory activity. We report the synthesis and sialidase inhibitory activity of glycoconjugates consisting of biflavonoids (1, 2) and sugars: 2-keto-3-deoxy-D-glycero-D-galactonononic acid (KDN, 3), N-acetyl-D-glucosamine (GlcNAc, 4), and N-acetyl-D-lactosamine (LacNAc, 5). The glycoconjugates (18R, 18S, 21R, 21S) of biflavonoids (1, 2) and GlcNAc (4) showed selective inhibitory activity against sialidase of influenza A virus H1N1 subtype. In particular, the inhibitory activity of 18S was similar to or higher than that of 5,7,4'-trihydroxy-8-methoxyflavone (F36) as a positive control. The glycoconjugate 18S showed the most potent inhibitory activity against sialidase of influenza A virus H1N1 subtype, with an IC50 of 48.5 μg/mL.

■ Catalytic Enantioselective Construction of trans-Fused 2,3,3a,4,5,9b-Hexahydro-1H-pyrrolo[3,2-c]quinoline Derivatives by Intramolecular [3+2]-Cycloaddition

Keigo Sato, Tetsuya Tsujihara,* Sho Inagaki, Tsunayoshi Takehara, Takeyuki Suzuki, and Tomikazu Kawano*

*Department of Medicinal and Organic Chemistry, School of Pharmacy, Iwate Medical University, 1-1-1 Idaidori, Yahaba , Iwate, Japan

Abstract

An enantioselective construction of trans-fused 2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolines via Cu-catalyzed asymmetric intramolecular [3+2]-cycloaddition is described. The method entails the use of glycine ester imines bearing trisubstituted activated olefins derived from the adducts of Morita-Baylis-Hillman reactions as substrates to afford the desired cycloadducts as single diastereomers. A series of trans-fused 2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinoline derivatives were obtained in 19%–93% yield and 80%–93% ee. These results demonstrate that trisubstituted activated olefins are eff

■ Concise Formal Synthesis on Solandelactone E Based on a Regioselective Cyclopropanation

Norihiko Kawasaki, Yu Kikuoka, Keita Komine, Hayato Fukuda, and Jun Ishihara*

*Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

A concise synthetic approach to solandelactone E has been developed based on a regio- and stereoselective cyclopropanation using Zn(CH2I)2·DME and butyldioxaborolane.

■ 12-epi-Briacavatolide B, a New Briarane Diterpenoid from the Octocoral Briareum stechei

Chia-Jung Liu, Hsin-Tzu Liu, Thanh Hao Huynh, Zhi-Hong Wen, Chia-Ching Liaw, Jih-Jung Chen, Jui-Hsin Su, and Ping-Jyun Sung*

*Department of Planning and Research, National Museum of Marine Biology and Aquarium, 2 Houwan Road, Checheng, Pingtung, Taiwan 944, Taiwan

Abstract

A new briarane-type diterpenoid, 12-epi-briacavatolide B (1), along with its known epimer, briacavatolide B (2), were purified from an octocoral identified as Briareum stechei. Spectroscopic approaches were used to reveal the structure of new briarane 1.