Figure 3
Synthesis of 1α,20S-dihydroxyvitamin D3. Reagents and conditions: (a) K2CO3, MeOH, r.t., overnight. (b) TBSCl, imidazole, DMF, r.t., overnight. (c) NaBH4, DCM: MeOH (1:1), 0 °C - r.t., overnight. (d) Ac2O, Et3N, DMAP, DCM, r.t., overnight. (e) TBAF, THF, r.t., 12 h. (f) DDQ, 1,4-dioxane, reflux, 4 h. (g) KOH, MeOH, r.t., 3 h. (h) TBSCl, imidazole, DMF, r.t., overnight. (i) KOH in MeOH, 30% H2O2, MeOH, −40 °C – 0 °C, 12 h. (j) Li, NH3 (liquid), −80 °C, 30 min; addition of starting material in THF, −80 °C, 2 h; −40 °C, 1 h; NH4Cl, −80 °C, 2 h. (k) Ac2O, Et3N, DMAP, DCM, r.t., overnight. (l) TBAF, THF, r.t., 48 h. (m) DMP, DCM, r.t., 12 h. (n) Dibromantin, AIBN, benzene: hexane (1:1), reflux 20 min; TBAB, THF, r.t., 75 min; TBAF, r.t., 50 min. (o) K2CO3, MeOH, r.t., overnight. (p) i) Mg, I2, 1-bromo-4-methylpentane, THF, reflux, 1 h; ii) 18, THF, 0 °C – r.t., overnight. (q) UVB irradiation, Et2O, 50 °C, 15 min; r.t., 10 d; HPLC, MeCN:H2O. AIBN, azobisisobutyronitrile; DDQ, 2,3-dichloro-5,6-dicyanobenzoquinone; DMP, Dess–Martin periodinane; DMAP, 4-dimethylaminopyridine; HPLC, high-performance liquid chromatography; TBAB, tetra-n-butylammonium bromide; TBAF, tetra-n-butylammonium fluoride; TBSCl, tert-butyldimethylsilyl chloride.
