Description
5-(1-Hydroxyethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (Acetyl Meldrum's acid) is a pharmaceutical intermediate compound used in the preparation of Vinaxanthone. Vinaxanthone is a selective inhibitor of signal transduction factor 3A, phospholipase C (PLC), and FabI, and exhibits antibacterial activity.
Synthesis
The general procedure for the synthesis of 5-(1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxo-4,6-dione from cyclic (sub)isopropyl malonate and acetyl chloride is as follows:
GENERAL METHOD: Method A (adapted from Srensen et al:)
1. To a dichloromethane solution of Meldrum acid (1 eq.) was added dropwise pyridine (2 eq.) at 0 °C and stirred for 15 min.
2. to the reaction mixture was added the corresponding acyl chloride (1 eq.).
3. The reaction mixture was stirred at 0 °C for 1.5 hours, followed by continued stirring at room temperature for 1.5 hours.
4. Upon completion of the reaction, the reaction was quenched with 2M hydrochloric acid and extracted with dichloromethane.
5. The organic layers were combined, dried with sodium sulfate, filtered and concentrated in vacuum.
6. the residue is purified by silica gel chromatography using a hexane solution of 5% to 10% ethyl acetate (containing 1% acetic acid) as eluent to afford the target product 5-(1-hydroxyethylidene)-2,2-dimethyl-1,3-dioxo-4,6-dione (acyl Meldrum acid derivatives, nos. 11a-e, j, l, p).
References
[1] Journal of Organic Chemistry, 2000, vol. 65, # 4, p. 1003 - 1007
[2] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 6, p. 1321 - 1340
[3] Acta Chimica Slovenica, 2013, vol. 60, # 2, p. 403 - 410
[4] Canadian Journal of Chemistry, 1992, vol. 70, # 5, p. 1427 - 1445
[5] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 10, p. 1303 - 1306
