Mendeleev Communications Electronic Version, Issue 4, 1999 (pp. 129–170) Simple synthesis of natural polyketides, 2-dodecanoyl-5-hydroxycyclohexane-1,3-dione and 2-dodecanoylresorcinol Vladimir G. Zaitsev,* Pavel M. Philipchenko and Fedor A. Lakhvich Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 220141 Minsk, Belarus. Fax: +375 172 63 7274; e-mail: prostan@ns.iboch.ac.by The title compounds were synthesised in two and three steps, respectively, starting from 5-hydroxycyclohexane-1,3-dione. 2-Dodecanoyl-5-hydroxycyclohexane-1,3-dione 1 was identified1 as the major component of the secretions of Stephanitis takeyai. It was prepared by a complex multistage synthesis including the construction of the cyclohexane ring containing a phenyldimethylsilyl substituent as a masked hydroxy group.2 The authors reported the easy aromatization of hydroxytriketone 1 due to the known succeptibility of b-hydroxyketones to dehydration.Recently, we reported the first synthesis of 5-hydroxycyclohexane- 1,3-dione 2.3 We have found that 5-hydroxydiketone 2 exists in solution mainly in the enolic form, and it takes part in reactions through its enol group.It gives little or no by-product aromatics in the absence of an acid. Based on this finding, we carried out a simple two-step synthesis of target compound 1 by the method developed earlier4 for regioisomeric 2-acyl-4- hydroxycyclohexane-1,3-diones. Acylation of 5-hydroxydiketone 2 with dodecanoyl chloride proceeds regiospecifically, affording enolacylate 3. The latter was then subjected to a smooth O–C isomerization into triketone 1† under the CN– catalysis. This method can be used as a general procedure for the synthesis of other 2-acyl-5-hydroxycyclohexane-1,3-diones.Moreover, these 5-hydroxyketones are the immediate synthetic precursors of natural bioactive 2-acylresorcinols.5 Thus, hydroxytriketone 1 was entirely converted into 2-dodecanoylresorcinol 4‡ when treated with a mineral acid.This work was supported by the Byelarussian Foundation for Basic Research (grant no. X97-109). † 2-Dodecanoyl-5-hydroxycyclohexane-1,3-dione 1. To a stirred solution of 0.39 g (3 mmol) of anhydrous 5-hydroxycyclohexane-1,3-dione 2 (mp 95–96 °C) and 0.25 ml (3.1 mmol) of pyridine in 30 ml of dioxane, 0.60 ml (2.5 mmol) of dodecanoyl chloride in 20 ml of dioxane was added dropwise, over 1 h at room temperature.The solvent was evaporated in vacuo, and 20 ml of CHCl3 was added to the residue. The solution was washed with 0.2 M HCl, H2O, brine, and then dried over MgSO4. The crude product after solvent evaporation was recrystallised from hexane giving 0.71 g (92%) of 3-dodecanoyl-5-hydroxycyclohex-2-en-1-one 3.Mp 43–44 °C. 1H NMR (200 MHz, CDCl3) d: 0.88 (t, 3H, Me, J 6.5 Hz), 1.27 (m, 16H, 4'–11'-CH2), 1.67 (m, 2H, 3'-CH2), 2.48 (t, 2H, 2'-CH2, J 7.5 Hz), 2.55 and 2.64 (2dd, 2H, 4,6-Ha, J 6.5 and 17 Hz), 2.70 (dd, 1H, 4- or 6-He, J 4 and 17 Hz), 2.88 (dd, 1H, 4- or 6-He, J 4 and 17 Hz), 4.43 (m, 1H, 5-H), 5.98 (s, 1H, 2-H). IR (KBr, n/cm–1): 3440 (br.), 1765, 1680, 1660, 1480, 1420, 1380, 1145, 1135, 1115, 1070.To a solution of 0.17 g (0.55 mmol) of enolacylate 3 and 0.24 ml (2.5 mmol) of Et3N in 30 ml of acetonitrile, 0.06 ml (0.6 mmol) of acetone cyanohydrin was added. The reaction mixture was allowed to stand for 3 h at room temperature, then the solvent was evaporated in vacuo, and the residue was worked up as above giving, after recrystallization from hexane, 0.16 g (94%) of 2-dodecanoyl-5-hydroxycyclohexane-1,3-dione 1.Mp 55–56 °C. Physical and chemical characteristics of synthetic 1 are the same as those published.2 ‡ 2-Dodecanoylresorcinol 4 was obtained by dehydration in an acid medium (2 drops of conc. HCl in 20 ml of acetone) of crude hydroxytriketone 1 synthesised as described above from 0.30 g (0.97 mmol) of enolacylate 3.After completing the dehydration reaction (3 h, control by TLC), the solvent was evaporated. The residue was dissolved in CHCl3, washed with H2O and brine, dried over MgSO4, and the solvent was evaporated giving, after recrystallization of the residue from hexane, 0.25 g (88%) of 2-dodecanoylresorcinol 4. Mp 85–86 °C. Physical and chemical characteristics of synthetic 4 are the same as those published.6 References 1 J.E. Oliver, W. R. Lusby and J. W. Neal, Jr., J. Chem. Ecol., 1990, 16, 2243. 2 J. E. Oliver, R. M. Waters and W. R. Lusby, Tetrahedron, 1990, 46, 1125. 3 V. G. Zaitsev and F. A. Lakhvich, Mendeleev Commun., 1998, 20. 4 V. G. Zaitsev, G. I. Polozov and F. A. Lakhvich, Tetrahedron, 1994, 50, 6377. 5 (a) R. A. Jurenka, J. W. Neal, Jr., R. W. Howard, J. E. Oliver and G. I. Blomquist, Comp. Biochem. Physiol., 1989, 93C, 253; (b) Y. Tsuda, Sh. Hosoi and Y. Goto, Chem. Pharm. Bull., 1991, 39, 18; (c) V. G. Zaitsev and F. A. Lakhvich, Mendeleev Commun., 1995, 224. 6 K. K. Purushotaman, A. Sarada and J. D. Connolly, J. Chem. Soc., Perkin Trans. 1, 1977, 587. O O HO OH O HO C11H23COCl; Py dioxane, 1 h, room temperature O O HO O H23C11 O O HO C11H23 O CN OH; Et3N MeCN HCl acetone OH OH C11H23 O 2 3 1 4 Received: 18th December 1999; Com. 98/1414