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KEYWORDS
Baylis-Hilman adduct
acetate;
4-hydroxycoumarin;
Annulated 2-pyrone;
Solvent-free
conditions.
Abstract. 4-hydroxycoumarin 2a and 4-hydroxy-6-methyl-pyran-2-one 2b were applied in a one-pot reaction with Baylis-Hillman adduct acetates 1 to form novel 3-benzyl-pyrano [3, 2-c] pyran-2, 5-diones 3 in high yields (70-85%). The synthesized framework is available in many biologically active moieties. The reaction was carried out under different conditions to achieve optimum conditions. The results indicated that Et^sub 3^N, as a base under solvent-free conditions, was optimum. The reaction procedure and purification method are mild and straightforward.
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1. Introduction
Generally, 2-pyrone derivatives are an important class of organic compound forming building blocks of many natural and biologically active compounds [1-2]. In particular, annulated pyrones exhibit outstanding natural and biological activities. For instance, Norneolambertellin (1), isolated from a mycroparasite Lambertella sp.1346, functions as an antifungal [3], fordianin A (2) and fordianin B (3) have cytotoxicity against A549 (human lung cancer) and human cervical carcinoma, coumestrol (4) acts as an anti-breast cancer [4-6] and Arisugacin A (5) possesses significance in the treatment of dementia such as Alzheimer's disease [7] (Figure 1).
Because of the importance of fused pyrones, several methods have been described for the synthesis of these frameworks. The synthesis of derivatives of 2H,5H-2,5-dioxo-3-pyrano[3,2c] benzopyranoic acids by the reaction of 3-formyl-4-hydroxycoumarin has been reported in low yields [8]. Mild conversion of 4-hydroxycoumarin to pyranobenzopyran was performed via a modified Pechman reaction [9]. In 2006, Sheibani et al. reported a one-pot synthesis of 2H,5H-pyrano[3,2-c]chromene-2,5-dione derivatives by the reaction of chlorocarbonyl ketenes with 4-hydroxycoumarin [10]. Leutbecher applied enzymatic biotransformation of 4-hydroxy-6-methyl-2H-pyran-2-one into coumestans and related heterocycles in 51 to 99% yields [11].
However, synthesis of the annulated pyrone skeleton is restricted by the lack of enough available methods to construct the desired ring bearing functional groups, and many of them are prepared in multistep procedures. As a result, extension of simple, ecient, green and, specifically, one-pot, methodologies for the synthesis of annulated 2-pyrone derivatives remains crucial.
The Baylis-Hillman reaction recently received considerable attention as a straightforward reaction to form C-C bonds [12-18]. Furthermore, adduct acetates of Baylis-Hillman have been utilized as a versatile synthon to form varieties of biologically active frameworks such as coumarines [19], quinolones [20],quinolines [21],benzazepines [22],...