西北农林科技大学：《有机化学 Organic chemistry》课程PPT教学课件（2017）McMurry OCB 3Ed Chapter 05 Stereochemistry at Tetrahedral Centers

Organic Chemistry with BiologicalApplications,3 Edition John McMurry Chapter 05 Stereochemistry at Tetrahedral Centers Onderstanding the causes and consequences of molecular handedness is crucial to understanding biological chemistry. Homework:P127:5.10:P132:5.16:P145b:5.32:5.36: By Junru Wang College of Chemistry and Pharmacy Room C206,Science Building Tel:87092829(O):Email:wangjr07@163.com

By Junru Wang College of Chemistry and Pharmacy Room C206, Science Building Tel: 87092829(O)；Email: wangjr07@163.com Organic Chemistry with Biological Applications, 3 rd Edition John McMurry Understanding the causes and consequences of molecular handedness is crucial to understanding biological chemistry. Chapter 05 Stereochemistry at Tetrahedral Centers Homework： P127:5.10; P132:5.16; P145b:5.32; 5.36;

Organic Chemistry with BiologicalApplications,3rEdition John McMurry Chapter 05 Stereochemistry at Tetrahedral Centers

Chapter 05 Stereochemistry at Tetrahedral Centers Organic Chemistry with Biological Applications, 3 rd Edition John McMurry

Main Contents Molecular Chirality Chiral carbon Absolute and Relative Configuration Stereoisomers without chiral carbons Properties of Enantiomers Diastereomers Resolution of Enantiomers Key Notes Chiralenantiomers;Chirality Chiralcenter Opticalrotations;RS,D/L;Diastereomers; Meso forms;Resolution ofenantiomers;

Main Contents ◼Molecular Chirality & Chiral carbon ◼Absolute and Relative Configuration ◼Stereoisomers without chiral carbons ◼Properties of Enantiomers & Diastereomers ◼Resolution of Enantiomers Key Notes Chiral enantiomers; Chirality & Chiral center; Optical rotations; R /S ，D/L; Diastereomers ; Meso forms; Resolution of enantiomers;

Chirality in nature I Natural amino acids are enantiomerically pure These are the building blocks of proteins and enzymes HO2C Me 入K7 H02C、 NH, NH2 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

胰岛素

Chirality in Nature Enantiomers of a chiral molecule Have same physical properties Usually have different biological properties (+)-Limonene (-)-Limonene (in oranges) (in lemons) @2007 Thomson Higher Education The two enantiomers of carvone: 香芹酮 spearmint Caraway(苋蒿，香菜)rye bread

Chirality in Nature Enantiomers of a chiral molecule：Have same physical properties； Usually have different biological properties The two enantiomers of carvone: spearmint Caraway(苋蒿，香菜) rye bread * 香芹酮

Biological Significance 比旋光度mp ◇肌肉运动--乳酸是右旋体，（+)-乳酸+3.82° 53℃ 必乳糖发酵-乳酸是左旋体，（·)-乳酸-3.82° 53℃ 必牛奶变酸--外消旋体，（士)-乳酸 无旋光度 18C OH OH (R)(-)-epinephrine enzyme active site enzyme-substrate complex natural epinephrine Better Fit....More Active 肾上腺素 OH OH Poor Fit....Less Active OH used in medicine as a heart stimulant, CH vasoconstrictor,and bronchial relaxant. 白色到褐色之间的晶体化合物用作心脏兴奋剂、 血管收缩剂和支气管肌松弛剂 (S)-(+)-epinephrine unnatural epinephrine does not fit the enzyme's active site

Biological Significance 肾上腺素 used in medicine as a heart stimulant, vasoconstrictor, and bronchial relaxant. 白色到褐色之间的晶体化合物.用作心脏兴奋剂、 血管收缩剂和支气管肌松弛剂 Better Fit….More Active Poor Fit…. Less Active 比旋光度 mp ❖肌肉运动---乳酸是右旋体，（+）-乳酸 + 3.82° 53℃ ❖乳糖发酵---乳酸 是左旋体，（﹣）- 乳酸 - 3.82° 53℃ ❖牛奶变酸---外消旋体， （±）- 乳酸 无旋光度 18℃ ＊

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

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

Many Pharmaceuticals Are Chiral! 米 Ibuprofen (Advil) Thalidomide: used as a sedative and anti-nausea drug 镇静剂和抗恶心

Many Pharmaceuticals Are Chiral! Ibuprofen (Advil) Thalidomide: used as a sedative and anti-nausea drug * * 镇静剂和抗恶心

手性药物：Why to resolve the racemic mixtures to obtain the single enantiomer? 镇静剂和杭恶心 镇静 Thalidomide 反应停 沙利度胺 Caused serious birth defects when taken by pregnant women!

Thalidomide 手性药物：Why to resolve the racemic mixtures to obtain the single enantiomer? 反应停 沙利度胺 镇静 镇静剂和抗恶心 Caused serious birth defects when taken by pregnant women!

Chiral pharmaceuticals Fluoxetine,a heavily prescribed medication sold under the trade name Prozac Racemic fluoxetine is an effective antidepressant but has no activity against migraine偏头痛 The pure S enantiomer works well in preventing migraine NHCH3 (S)-Fluoxetine (prevents migraine) 2007 Thomson Higher Education

Chiral pharmaceuticals ▪ Fluoxetine, a heavily prescribed medication sold under the trade name Prozac ▪ Racemic fluoxetine is an effective antidepressant but has no activity against migraine偏头痛 ▪ The pure S enantiomer works well in preventing migraine