Chiral pharmaceuticals Dramatic examples of how a change in chirality can affect the biological properties of a molecule are seen in many drugs Fluoxetine,a heavily prescribed medication sold under the trade name Prozac -Racemic fluoxetine is an effective antidepressant but has no activity NHCH3 against migraine -The pure S F30 enantiomer works well in preventing (S)-Fluoxetine migraine偏头痛 (prevents migraine) 2007 Thomson Higher Educalion
Chiral pharmaceuticals Dramatic examples of how a change in chirality can affect the biological properties of a molecule are seen in many drugs Fluoxetine, a heavily prescribed medication sold under the trade name Prozac Racemic fluoxetine is an effective antidepressant but has no activity against migraine The pure S enantiomer works well in preventing migraine偏头痛
药物作用有效成分另一对映体用 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
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
Worldwide sales of chiral drugs 1500 1330 1180 uolll!w 1200 934 900 812 706 614 600 452 100 350 300 19931994199519961997199819992000 Chem.Eng.News,2001,Vol.79,No.40,pp79
Worldwide sales of chiral drugs 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 $
Chirality in nature l Natural amino acids are enantiomerically pure These are the building blocks of proteins and enzymes NH> Ho6 alanine phenylalanine histidine Why this enantiomer?Who knows... But why just one enantiomer is more obvious... 胰岛素 Insulin C254H3776507656 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
胰岛素
Chirality in Nature Enantiomers of a chiral molecule Have same physical properties Usually have different biological properties (+)enantiomer of limonene has the odor of oranges (-)enantiomer of limonene has the odor of lemons (+)-Limonene (-)-Limonene (in oranges) (in lemons】 2007 Thomson Higher Education
Chirality in Nature Enantiomers of a chiral molecule Have same physical properties Usually have different biological properties (+) enantiomer of limonene has the odor of oranges (–) enantiomer of limonene has the odor of lemons