A simple and efficient approach to the synthesis of 4H-furo[3,4-b]pyrans via a three-component reaction of isocyanides Ahmad Shaabani * , Ebrahim Soleimani, Afshin Sarvary, Ali Hossein Rezayan Department of Chemistry, Shahid Beheshti University, PO Box 19396-4716, Tehran 19839-4716, Iran article info Article history: Received 5 March 2008 Revised 28 May 2008 Accepted 5 June 2008 Available online 10 June 2008 Keywords: Multi-component reaction Isocyanide Tetronic acid 4H-furo[3,4-b]pyran abstract A three-component reaction of an isocyanide, a dialkyl acetylenedicarboxylate, and tetronic acid in dichloromethane at room temperature afforded 4H-furo[3,4-b]pyran derivatives. These compounds are closely related with ring systems, TAN-2483B, TAN-2483A, and FD-211 which have a broad spectrum of biological activity. Ó 2008 Published by Elsevier Ltd. Multi-component reactions (MCRs) have been frequently used by synthetic chemists as a facile means to generate molecular diversity from bifunctional substrates that react sequentially in an intramolecular fashion. 1–4 Devising such types of MCRs that achieve the formation of multiple bonds in a single operation is one of the major challenges in modern organic synthesis. 5–9 As such processes avoid time-consuming and costly purification pro- cesses, as well as protection–deprotection steps, they are inher- ently more environmentally benign and atom-economic. 10,11 They provide a powerful tool toward the one-pot synthesis of di- verse and complex compounds as well as small and drug-like het- erocycles. 12 MCRs that involve isocyanides are by far the most versatile reactions in terms of scaffolds and number of accessible compounds. 1–5,13 Mizoue and co-workers reported the isolation of waol A (FD- 211), which has a broad spectrum of activity against cultured tu- mor cell lines, including adriamycin-resistant HL-60 cells, from the fermentation broth of Myceliophthora lutea TF-0409. 14 TAN- 2483B and TAN-2483A which have closely related compounds with this ring system (FD-211) show strong c-src kinase inhibitory action and inhibit PTH-induced bone resorption of a mouse fe- mur. 15 Other related compounds include the antibacterial massar- ilactone B, which was isolated by Gloer from the freshwater aquatic fungus Massarina tunicata in 2001. 16 Fusidilactones A and B isolated by Krohn from an endophytic Fusidium sp. in 2002 17 show good antifungal activity against Eurotium repens and Fusarium oxysporum (Fig. 1). Very recently, Snider and co-workers reported the synthesis of TAN-2483A, massarilactone B, fusidilactone B, and waol A (FD- 211) via multi-step approach under very hard reaction conditions. 18,19 As part of our continuing interest in the development of new synthetic methods in heterocyclic chemistry and our interest in isocyanide-based multi-component reactions, 20–27 herein we de- scribe an efficient synthesis of 4H-furo[3,4-b]pyrans 4 via the reac- tion of an isocyanide 1 with an dialkyl acetylenedicarboxylate 2 and tetronic acid 3 in high yields without using any catalyst at ambient temperature 28 (Scheme 1). 0960-894X/$ - see front matter Ó 2008 Published by Elsevier Ltd. doi:10.1016/j.bmcl.2008.06.014 * Corresponding author. Tel.: +98 21 29902800; fax: +98 21 22403041. E-mail address: a-shaabani@cc.sbu.ac.ir (A. Shaabani). O O O H HO Me H Me H H O O O HO Me H Me H H H O O O HO H Me H H H Me O O O HO Me Me OH O O O HO Me OH Me Me Et O O O HO Me OH Me OH Et Me H H TAN-2483B TAN-2483A FD-211 massarilactone B massarilactone A fusidilactone B Figure 1. Structures of TAN-2483B, TAN-2483A, FD-211, massarilactone B, mas- sarilactone A, and fusidilactone B. Bioorganic & Medicinal Chemistry Letters 18 (2008) 3968–3970 Contents lists available at ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl