西北农林科技大学：《有机化学 Organic chemistry》课程教学课件（2009）Chapter 04 stereochemistry

林 Sect D Conformation analysis Stereochemistry ■

西北农林科技大学理学院 By Junru Wang Email: wangjr07@163.com Sect D Sect D Conformation analysis Conformation analysis & Stereochemistry & Stereochemistry

Me2N. Ph 0 t darvo enzyme Darvon is a painkiller. Its enantiomer is an anticough agent. 手性药物 Why to resolve the racemic mixtures to obtain the single enantiomer?

手性药物 Why to resolve the racemic mixtures to obtain the single enantiomer?

Many pharmaceuticals are chiral! COOH 米 Ibuprofen (Advil) Thalidomide: used as a sedative and anti-nausea drug

Many pharmaceuticals are chiral! N N O O O O H H COOH H * Ibuprofen (Advil) Thalidomide: used as a sedative and anti-nausea drug *

Other times,the different interaction of enantiomers with chiral biological molecules is serious. The two enantiomers of Thalidomide: beneficial sedative 米 and anti-nausea drug Caused serious birth defects when taken by pregnant women!

Other times, the different interaction of enantiomers with chiral biological molecules is serious. N N O O O O H H N N O O O O H H * * The two enantiomers of Thalidomide: beneficial sedative and anti-nausea drug Caused serious birth defects when taken by pregnant women!

东林 手性药物 Why to resolve the racemic mixtures to obtain the single enantiomer? 镇静 thalidomide 反应停 (Schudein 1982 and Moow 199

手性药物 ※Why to resolve the racemic mixtures to obtain the single enantiomer? thalidomide N N O O O O * 反应停 镇静

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