ACETYLLOVASTATIN synthesis

Yield:81189-92-6 84%

Reaction Conditions:

with pyridine at 20; for 2.5 h;Inert atmosphere;

Steps:

(S)-2-Methyl-butyricacid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-acetoxy -6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester (2a)

To a solution of lovastatin (1, 1.00 g, 2.48 mmol) in pyridine (5 mL) was added Ac₂O (2.5mL). The resulting solution was stirred under N₂ at RT for 2.5 h.The reaction mixture was diluted with EtOAc (50 mL) and the solution was washedwith 1N HCl_(aq)(3 x 25 mL), 10% NaHCO_3(aq) (25 mL), anddistd H₂O (30 mL). Then the organic layer was dried over Na₂SO₄,filtered and the solvent removed in vacuo. The residue was purified by silicagel chromatography (EtOAc: n-hexane=1:4) to give 2a (926 mg, 84%). IR (KBr) 2973,2360, 1844, 1732, 1683, 1652, 1540, 1456, 1373 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ 5.97 (d, J = 9.7 Hz, 1H), 5.76 (dd, J = 6.1, 9.6 Hz, 1H), 5.50 (s, 1H), 5.36(dd, J = 3.1, 6.1 Hz, 1H), 5.21 (dt, J = 1.7, 3.5 Hz, 1H), 4.45 (m, 1H), 2.73(d, J = 5.3 Hz, 1H), 2.70 (dd, J = 1.5, 3.50 Hz, 1H), 2.46 (m, 1H),2.32 (dd, J = 7.0, 13.8 Hz, 2H), 2.22(m, 1H), 2.06 (s, 3H), 2.03 (m, 2H), 1.90 (dd, J = 2.4, 7.7 Hz, 1H), 1.69 (m, 2H), 1.63 (m, 2H), 1.43 (m, 3H),1.23 (m, 1H), 1.08 (d, J = 6.9 Hz, 3H),1.05 (d, J = 7.4 Hz, 3H), 0.87 (d, J = 7.1 Hz, 3H), 0.83 (t, J = 7.4 Hz, 3H). ESI-MS m/z : 469.3 (M+Na)⁺.

References:

Lin, Ruo-Kai;Lin, Yuh-Feng;Hsu, Ming-Jen;Hsieh, Chang-Lin;Wang, Chen-Yu;Huang, Chih-Chiang;Huang, Wei-Jan [Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,# 22,p. 5528 - 5533] Location in patent:supporting information