A simple and efficient approach to the synthesis of furopyran derivatives: four-component reaction of isocyanides with arylidene-substituted Meldrum’s acid

Abstract

Multicomponent reactions (MCRs) are powerful tools for the synthesis of complex biologically relevant molecules. The atom economy of MCRs, their convergent character, operational simplicity, the structural diversity [1, 2], and complexity of the resulting molecules make this type of reactions exceptionally useful for discovery and optimization processes in the pharmaceutical industry. Isocyanide-based multicomponent reactions (IMCRs) are easily performed using readily available starting materials and tolerate a variety of functional groups. A plethora of variations and subsequent transformations provide access to a fairly large number of unique structures that would otherwise require lengthy preparations. Therefore, IMCRs present an ideal tool for accessing large and diverse chemical space and have been used since the advent of combinatorial chemistry to construct such libraries of compounds [3]. During the past decade, IMCRs gained significant interest within the scientific community as an efficient, convenient, time-saving, and atom-economical approach to a variety of drug-like small heterocyclic molecules [4–12]. The furopyran skeleton is frequently found in various natural and biological products. Waol A (FD-211) has a broad spectrum of activity against cultured tumor cell lines [13]; the closely related compounds TAN-2483A and TAN-2483B show strong c-Src kinase inhibitory action and a potential for treatment and prevention of osteoporosis [14]. Antibacterial Massarilactone B was isolated by Gloer from the freshwater aquatic fungus Massarina tunicata [15]. Usually these and similar compounds are synthesized via multistep approach, often under very forcing reaction conditions [16–17]. The reactions of alkylidene- and arylidene-substituted Meldrum's acid with alkyl and aryl isocyanides have been extensively studied, and diverse products were obtained [18–21]. We have been interested in isocyanide-based multicomponent reactions and synthesis of heterocyclic skeletons [18, 20–22]. Recently, we have reported the reaction of alkylidene-substituted Meldrum's acid and isocyanide that led to new furo[3,4-b]pyran derivatives [23]. To expand this method (3+1 IMCR) for synthesis of novel furo[3,4-b]pyran derivatives, we wish to report the result of this approach for the synthesis of some novel furopyran derivatives via reaction of arylidene-substituted Meldrum's acid and isocyanides.