Figure 2.
Linear synthesis of eldecalcitol (5) from lithocholic acid (6) via 25-hydroxycholesterol (17). Reagents and conditions: a: NBS/dioxane, 40°C to 55°C. b: LiCO3/DMF, 90°C. c: HCl/MeOH, rt. d: TsOH/Ac2O, 85°C. e: NaBH4/MeOH/THF, 0°C. f: DHP/Amberlyst 15/CH2Cl2, rt. g: Red-Al/benzene, reflux. h: NBS/Ph3P/NaHCO3/DMF, 0°C. i: 2-methyl-1,3-dithiane/n-BuLi/THF/n-hexane, −78°C to 4°C. j: MeI/acetone/H2O, reflux. k: MeMgBr/THF, −5°C to 0°C. l: (Oi-Pr)3Al/cyclohexanone. m: DDQ/AcOEt. n: NaOEt/EtOH. o: NaBH4/MeOH/THF. p: Ac2O/DMPA/pyridine, rt. q: NBS/AIBN/n-hexane, reflux. r: γ-collidine/toluene, reflux. s: KOH/MeOH, rt. t: PTAD/CH2Cl2, rt. u: TBSCl/imidazole. v: MCPBA/CH2Cl2. w: DMI, 140°C. x: TBAF/THF. y: HO(CH2)3OH/t-BuOK, 110°C. z: 400 W high pressure mercury lamp/THF, 0°C then reflux without mercury lamp.