河北医科大学药学院 The stereo structure 3D model of strychnine: C21H22N202 In 1956 the synthesis of reserpine has become a model of elegant technique and has been used for the commercial production of this tranquilizer. MF: MW:609 H CH.OOc OCH reserpine The total synthesis of reserpine.J.Am.Chem.Soc.1956,78: 2023-2025,2057. The total synthesis of reserpine.Tetrahedron.1958,2:1-57.2 天然药物化学教研室
河北医科大学药学院 天然药物化学教研室 11 21 The stereo structure & 3D model of strychnine: N O O N H H H H C21H22N2O2 * * N N O O H H * * * * 22 CH3O OCH3 OCH3 OCH3 reserpine N H OCH3 OC O H H CH3OOC H N In 1956 the synthesis of reserpine has become a model of elegant technique and has been used for the commercial production of this tranquilizer. ⊙ The total synthesis of reserpine. J. Am. Chem. Soc. 1956, 78: 2023-2025, 2057. ⊙ The total synthesis of reserpine. Tetrahedron. 1958, 2:1-57. rauvolfia serpentina L. MF: C33H40N2O9 MW: 609
河北医科大学药学院 The stereo structure of reserpine: OCH CH MF:C3HaoN2O MW:609 Woodward's total synthetic route of reserpine 一地一 袋格一装数 (next page) 天然药物化学教研室 12
河北医科大学药学院 天然药物化学教研室 12 23 OCH3 OCH3 OCH3 COOCH3 * * * * * * OCH3 H H N NH OCH3 H H OC O The stereo structure of reserpine: MF: C33H40N2O9 MW: 609 24 O O HOOC CH2 + O O H H COOH NaBH4 O H H COOH OH PhO3H O H H COOH OH O Ac2O / NaOAc O H H O C O O Al(OPr-i)3 O O H H H O NaOMe O O H H H O H OMe O O H H H O H OMe Br HO NBS / H2SO4 (aq.) H H H H OMe O HOOC OH Woodward`s total synthetic route of reserpine: （next page）
河北医科大学药学院 Woodward's total synthetic route of reserpine (next page) Woodawrd's total synthetic route of reserpine: 天然药物化学教研室
河北医科大学药学院 天然药物化学教研室 13 25 （next page） 1) CH2N2 2) Ac2O / Py 3) OsO4 H H H OMe O MeOOC OCOMe OH OH 1) HIO4 2) CH2N2 H H H OMe MeOOC OCOMe CHO MeOOC MeO N OCH3 H H CH3OOC O OCOMe H N MeO NH NH2 MeO H N N OCH3 H H CH3OOC OCOMe H 1) POCl3 2) NaBH4 Woodward`s total synthetic route of reserpine: 26 1) KOH 2) HCl 3) DCC / Py MeO H N N OCH3 H H C H O O MeOH MeO H N N OCH3 H H MeOOC H OH CH3O OCH3 OCH3 OCH3 reserpine N H OCH3 OC O H H CH3OOC H N OCH3 OCH3 OCH3 C O Cl Woodawrd`s total synthetic route of reserpine :
河北医科大学药学院 Woodward finished the total synthesis of lysergic acid in 1956,too. MF:CIHN2O2 MW:268 lysergic acid stereo structure of lysergic acid (麦角酸) Woodward's subsequent achievements included the syntheses of chlorophyll(1960),tetracycline (1962),colchicine (1963),and cephalosporin C 1966. Chlorophyll A MF:N Mg MW:893.5 pRCHOCH-CH hyll D R=-CHg R'=-CHO (叶绿素) OThe total synthesis of chlorophyll.J.Am.Chem.Soc.,1960, 82:3800-3802. 天然药物化学教研室 14
河北医科大学药学院 天然药物化学教研室 14 27 Woodward finished the total synthesis of lysergic acid in 1956, too . MF: C16H16N2O2 MW: 268 ⊙ The total synthesis of lysergic acid. J. Am. Chem. Soc. 1956, 78: 3087-3014. stereo structure of lysergic acid （麦角酸） （麦角酸） N NH H C O HO lysergic acid 28 N N N Mg N R` R O O O COOCH3 3 chlorophyll A R= -CH3 R`= -CH=CH2 chlorophyll B R= -CHO R`= -CH=CH2 chlorophyll D R= -CH3 R`= -CHO （叶绿素） Woodward`s subsequent achievements included the syntheses of chlorophyll (1960), tetracycline (1962), colchicine (1963), and cephalosporin C (1966). ⊙The total synthesis of chlorophyll. J. Am. Chem. Soc., 1960, 82: 3800-3802. Chlorophyll A MF: C55H72O5N4Mg MW: 893.5