Synthesis
Sodium borohydride (27 mg, 0.70 mmol, 40 eq.) was added to a stirred solution of (-)-cephathione (S9) (5.5 mg, 18 μmol, 1.0 eq.) in methanol (0.65 mL) at -78 °C. The resulting white mixture was continued to be stirred at -78 °C for 10 minutes, followed by a slow warming to 25 °C and stirring at this temperature for 1 hour. Upon completion of the reaction, the mixture was diluted with water (30 mL) and extracted with dichloromethane (4 x 15 mL). The organic phases were combined, dried with sodium sulfate, gravity filtered, and the filtrate was concentrated by rotary evaporation to afford the target product (-)-1 (5.2 mg, 95% yield) as a light yellow film. Thin layer chromatography (TLC) showed an Rf value of 0.08 (unfolding agent: 10% methanol/dichloromethane). The structure of the product was confirmed by 1H NMR (500 MHz, CDCl3), IR and HRMS (ESI): 1H NMR δ 6.68 (s, 1H, ArH), 6.65 (s, 1H, ArH), 5.90 (s, 2H, OCH2O), 4.93 (s, 1H, vinyl H), 4.76 (d, 1H, J = 9Hz, CH(OH )), 3.73 (s, 3H, OCH3), 3.68 (d, 1H, J = 9 Hz, ArCHCH(OH)), 3.35 (m, 1H, CH2), 3.08 (m, 1H, CH2), 2.92 (dd, 1H, J = 12, 11, 7 Hz, CH2), 2.54-2.62 (m, 2H, CH2), 2.36 (ddd, 1H, J = 14, 7Hz, CH2), 2.00 (m, 1H, CH2), 1.60-1.90 (m, 4H, CH2); IR (pure film) 3411 (broad peaks, weak), 2926 (medium), 1651 (medium), 1503 (medium), 1486 (strong), 1222 (strong) cm-1; HRMS (ESI) m/z: C18H22NO4 ([M+H]+) calculated value 316.1549, measured value 316.1559.
References
[1] Journal of the American Chemical Society, 2006, vol. 128, # 32, p. 10370 - 10371
[2] Chemistry - A European Journal, 2008, vol. 14, # 14, p. 4293 - 4306
[3] Patent: WO2009/148654, 2009, A2. Location in patent: Page/Page column 135
[4] Phytochemistry (Elsevier), 1973, vol. 12, p. 2987 - 2991
