药品安全与药物手性

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dextrarotatory – d or (+)
levorotatory- l (-)
Terms for non-superimposable images: Optical isomers Optical antipodes Enantiomers
identical physical/chemical properties
欧洲、日本。。。。。。
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Enantiomeric interactions with a chiral biological macromolecule (Easson-Stedman model).
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NOMENCLATURE
CHIRAL CARBON: A carbon atom which has 4 different ligands attached and is thereby asymmetric.
Result is: nonsuperimposable mirror images rotate pwk.baidu.comlarized light
e.g., R-(-)- levorotatory, but with absolute configuration R
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STEREOCHEMISTRY CONSIDERATIONS
Most natural organic products, the essential products of life, are asymmetric ... This established perhaps the only well marked line of demarcation that can at present be drawn between the chemistry of dead matter and the chemistry of living matter.
H 3 CO
H
CH=CH 2
H
N
HO
H
N
Q u i n i n e [ 8 S , 89 R/1]0/2020
N
E p iq u in in e [8S , 9S ]
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PREFIXES USED TO DENOTE CHIRAL PROPERTIES
PREFIX d-/l-
D-/L-
R-/S-
PROPERTY Rightward (dextro), clockwise/Leftward
以单个对映体给药509 种
以外消旋给药8种
化学合成药物 1327种
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非手性799种 手性528种
以单个对映体给药61种
以外消旋给药467种
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农药 550种
天然农药 13种
非手性0种
手性13种
以单个对映体13种 以外消旋应用0种
非手性447种
化学合成农药 537种
手性90种
以单个对映体给药7 种
以外消旋体或异构体 混合物应用83种
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美 国 FDA'S POLICY STATEMENT FOR THE
DEVELOPMENT OF NEW STEREOISOMERIC
DRUGS,1992 中国SFDA:手性药物药学研究技术指导原则 (HGPH8-1),2006年6月
Canada Minister of Health ,GUIDANCE FOR INDUSTRY, Stereochemical Issues in Chiral Drug Development
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穿龙薯蓣（左手性）
常青油麻藤 （右手性 ）
在植物界许多藤本植物的茎是右手性的， 少量是左手性的，一部分则不显现手性。
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d
2
S
c
d
d
a
1
C
a
c
b
C
c
a
b
c
d
d
c
3 b
a
a
b
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b 5
N a
c
a
b
C
4
C
C
a
b
d
S
c
a
b
N a
c
Racemic mixture: d, l or +,-
Ex: d,l-propranolol
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H 3 CO
H
CH=CH 2
H
N
H
OH
H 3 CO
H CH=CH 2
N H
H
OH
N Q u in id in e [8R , 9S ]
H 3 CO
H CH=CH 2
N H
HO
H
N
E p iq u in id in e [8R , 9R ]
(leuvlo), counterclockwise, optical rotation. Used interchangably with (+)/(-) Rightward/leftward arrangement of substituents about chiral center (archaic, used for amino acids & carbohydrates) Rightward (rectus)/leftward (sinister) arrangement of substituents about chiral center (modern, used for drugs)
第十章、药品安全与药物的手性
/药物分析与药物代谢实验室/
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手性（chirality）一词源于希腊词 "手"，指左手与右手的差异特征。
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左手性者为葎草(Humulus scandens)，图中以A标出 ，桑科，也叫拉拉秧，叶 酷似啤酒花的叶。
右手性者为牵牛(Pharbitis nil)，以B标出，被缠绕的 植物为杨树。
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CO2
H H3C
NH 2
L-(+) alanine
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CO2
H H2N
CH3
D-(-) alanine
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rotation = configuration
R – rectus or D S – sinister or L
Thermodynamic equilibrium – 50:50 mixture
Louis Pasteur, circa. 1848
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Therapeutic Armamentarium
Non-optically active Drugs (40%)
药物 1850种
Optically active drugs (60%)
天然和半合成药物 523种
非手性6种 手性517种