Scheme 3.
Synthesis of triptolide (1) through Compound 14. ⅰ) H2, Pd/C, NH(OMe)MeˑHCl, CDI, Isopropenyl magnesium bromide; ⅱ) NaBH4, CeCl3ˑ7H2O, CH3C(OEt)3, CH3CH2COOH, reflux; ⅲ) LiOH, NH(OMe)MeˑHCl, CDI; ⅳ) Trimethylsilyl lithium acetylide, -78 ℃ to -20 ℃; ⅴ) compound 19, HCOOH, TEA, THF; ⅵ) K2CO3, TBSCI, imidazole; ⅶ) InBr3 (20%), -20 ℃; ⅷ) BH3ˑTHF, H2O2, 3N NaOH; ⅸ) NaH, PMBCI, PTSA; ⅹ) Jones reagent, LiHMDS, Tf2NPh, -78 ℃ to rt; ⅹⅰ) DDQ, CO, Pd(PPh3)4, Bu3N, LiCl, 80 ℃; ⅹⅱ) Rh(PPh3)3Cl, Et3SiH, toluene reflux; ⅹⅲ) I2, AgOTf; ⅹⅳ) Pb(dba)2, TBAF, compound 29, 5% Pd/C.