第5章立体化学 Stereochemistry
2 第5章 立 体 化 学 Stereochemistry
enzyme Me Me2N P Et darvon Darvon is a painkiller. Its enantiomer is an anticough agent
3
Biological Significance of Chirality Enantiomers of Epinephrine H3C⊕ Enzyme Anionic Flat area Anionic Flat area site site Not Occupied Occupied (+)-Epinephrine (-)-Epinephrine Poorer Fit D Less Active Better Fit More Active
4 ◆Biological Significance of Chirality
手性药物 的工 COOH 米 Ibuprofen (Advil) 日异丁苯丙酸，布洛芬（抗炎、镇痛药） 反应停 5
5 N N O O O O H H COOH H 手性药物 Ibuprofen (Advil) 异丁苯丙酸,布洛芬(抗炎、镇痛药) 反应停 * *
侣里 beneficial sedative 米 and anti-nausea drug Caused serious birth 米 defects when taken by pregnant women!
6 N N O O O O H H N N O O O O H H * beneficial sedative and anti-nausea drug * Caused serious birth defects when taken by pregnant women!
手性药物 中888是 镇静 thalidomide 反应停
7 thalidomide N N O O O O * 手性药物 反应停 镇静
药物作用有效成分另一对映体作用 反应停 镇静 S R致畸 Thalidomide 乙胺丁醇 抗结核 SS RR导致失明 心得安 心脏病 S R抑制性欲 Propranolol 氯霉素 抗菌 S R抗菌活性低 萘必洛尔 治疗高血压 右旋 左旋舒张血管 酮基布洛芬 抗炎 S R防治牙周病 ketoprofen 8
8 药 物 作用 有效成分 另一对映体作用 反应停 镇静 S R 致畸 Thalidomide 乙胺丁醇 抗结核 SS RR 导致失明 心得安 心脏病 S R 抑制性欲 Propranolol 氯霉素 抗菌 S R 抗菌活性低 萘必洛尔 治疗高血压 右旋 左旋 舒张血管 酮基布洛芬 抗炎 S R 防治牙周病 ketoprofen
Wosldwide sales of chiral drugs 1500 1330 O!l! 1200 1480 934 目 900 812 706 614 600 5 350 300 0 19931994199519961997199819992000 Chem.Eng.News,2001,Vol.79,No.40,pp79 6,000 5,000 4,000 3.000 2,000 1000 0 2009 2010 2011 2016 ☐Chiral synthesis □Chiral analysis ☐Chiral resolution Source:BCC Research
Chem. & Eng. News, 2001, Vol. 79, No. 40, pp79 350 452 614 812 1330 706 934 1180 0 300 600 900 1200 1500 1993 1994 1995 1996 1997 1998 1999 2000 100 million $ Worldwide sales of chiral drugs
Chirality in nature l Natural amino acids are enantiomerically pure These are the building blocks of proteins and enzymes HO2CMe NH> NH2 Ho alanine phenylalanine histidine Why this enantiomer?Who knows... But why just one enantiomer is more obvious... 胰岛素 1ns如m C254H377M6507656 Insulin is made of 2 peptide chains-1x30 amino acids 1x21 amino acids Potentially 2.25 x 1015 diastereoisomers ● A relatively small protein is ribonuclease at 124 amino acids or Potentially 2.13 x 1037 diastereoisomers
10 胰岛素
自然界的手性 对映异构体： ·物理性质相同 ■生物性能不同 (+)-Limonene (-)-Limonene (in oranges) (in lemons) 2007 Thomson Higher Education
11 自然界的手性 ❖对映异构体： ◼物理性质相同 ◼生物性能不同