e-content of Stereochemistry for Pharmacy and Chemistry students.
contents includes Isomerism, Chirality, Stereoisomers, Enantiomer, Diastereomer, Cis And Trans Configuration ,L And D Configuration ,R And S Configuration and Importance of the chirality in drugs ,Intravenous anaesthetics , etc.
Stereochemistry is the ‘chemistry of space’ , that is stereochemistry deals with the spatial arrangements of atoms and groups in a molecule.
Stereochemistry can trace its roots to the year 1842 when the French chemist Louis Pasteur made an observation that the salts of tartaric acid collected from a wine production vessel have the ability to rotate plane-polarized light, whereas the same salts from different sources did not have this ability.
Isomers are compounds that contain exactly the same number of atoms, i.e., they have exactly the same empirical formula, but differ from each other by the way in which the atoms are arranged.
Constitutional isomers, also known as structural isomers, are specific types of isomers that share the same molecular formula but have different bonding atomic organization and bonding patterns.
Stereoisomers are molecules having the same molecular formula and the atomic arrangement, but differ in their spatial arrangement.
Geometric isomers are two or more coordination compounds which contain the same number and types of atoms, and bonds (i.e., the connectivity between atoms is the same), but which have different spatial arrangements of the atoms.
There are 2 types of geometric isomers, ‘cis’ and ‘trans’. -cis isomers: when similar groups are present on the same side of the double bonds, then they are termed as cis. - trans isomers: when similar groups are present on the opposite sides of the double bonds then they are called trans isomers.
cis-diethylstilbestrol has only 7% of the estrogenic activity of trans-diethylstilbesterol.
Cisplatin have anticancer activity where ae trans platin is an inactive compound.
In chemistry, a molecule or ion is called chiral if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes.
Chirality is the property of being non identical to ones mirror image.
Chiral center is defined as the atom bearing 4 different atoms or group of atoms.
Molecules that form nonsuperimposable mirror images, and thus exist as enantiomers, are said to be chiral molecules.
For a molecule to be chiral, it cannot contain a plane of symmetry.
The term enantioselectivity refers to the efficiency with which the reaction produces one enantiomer.
Enantiomers are stereoisomers that are non-superimposable mirror images.
Have identical properties.
Similar shapes
Diastereomers are stereoisomers that are non superimposable and are not mirror images.
Have distinct physical properties.
Have different molecular shapes.
Enantiomers consist of a pair of molecules that are mirror images of each other and are not superimposable.
When a molecule contains only one chiral centre , the two stereoisomers are known as enantiomers.
These may be referred to or labelled using the configurational descriptors as either:
R(rectus meaning right handed) or S(sinister meaning left handed),
D(dextrorotatory)or L (laevorotatory)
E-Entgegen or Z- Zusamen
Analog design is usually defined as the modification of a drug molecule or of any bioactive compound in order to prepare a new molecule showing chemical and biological similarity with the original model compound
Presented by Dhanashree Kavhale. M. Pharm.(Pharmaceutical Chemistry) 1st year.
Various organic named reactions are there in Advanced Organic Chemistry I, as some of them are explained along with their mechanism.
stereochemistry and drug action ; basic introduction about stereochemistry and stereoisomers ; pharmacokinetic and pharmacodynamics concept of stereochemistry ; easson Stedman hypothesis ; stereo selectivity criteria .
Stereochemistry is the ‘chemistry of space’ , that is stereochemistry deals with the spatial arrangements of atoms and groups in a molecule.
Stereochemistry can trace its roots to the year 1842 when the French chemist Louis Pasteur made an observation that the salts of tartaric acid collected from a wine production vessel have the ability to rotate plane-polarized light, whereas the same salts from different sources did not have this ability.
Isomers are compounds that contain exactly the same number of atoms, i.e., they have exactly the same empirical formula, but differ from each other by the way in which the atoms are arranged.
Constitutional isomers, also known as structural isomers, are specific types of isomers that share the same molecular formula but have different bonding atomic organization and bonding patterns.
Stereoisomers are molecules having the same molecular formula and the atomic arrangement, but differ in their spatial arrangement.
Geometric isomers are two or more coordination compounds which contain the same number and types of atoms, and bonds (i.e., the connectivity between atoms is the same), but which have different spatial arrangements of the atoms.
There are 2 types of geometric isomers, ‘cis’ and ‘trans’. -cis isomers: when similar groups are present on the same side of the double bonds, then they are termed as cis. - trans isomers: when similar groups are present on the opposite sides of the double bonds then they are called trans isomers.
cis-diethylstilbestrol has only 7% of the estrogenic activity of trans-diethylstilbesterol.
Cisplatin have anticancer activity where ae trans platin is an inactive compound.
In chemistry, a molecule or ion is called chiral if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes.
Chirality is the property of being non identical to ones mirror image.
Chiral center is defined as the atom bearing 4 different atoms or group of atoms.
Molecules that form nonsuperimposable mirror images, and thus exist as enantiomers, are said to be chiral molecules.
For a molecule to be chiral, it cannot contain a plane of symmetry.
The term enantioselectivity refers to the efficiency with which the reaction produces one enantiomer.
Enantiomers are stereoisomers that are non-superimposable mirror images.
Have identical properties.
Similar shapes
Diastereomers are stereoisomers that are non superimposable and are not mirror images.
Have distinct physical properties.
Have different molecular shapes.
Enantiomers consist of a pair of molecules that are mirror images of each other and are not superimposable.
When a molecule contains only one chiral centre , the two stereoisomers are known as enantiomers.
These may be referred to or labelled using the configurational descriptors as either:
R(rectus meaning right handed) or S(sinister meaning left handed),
D(dextrorotatory)or L (laevorotatory)
E-Entgegen or Z- Zusamen
Analog design is usually defined as the modification of a drug molecule or of any bioactive compound in order to prepare a new molecule showing chemical and biological similarity with the original model compound
Presented by Dhanashree Kavhale. M. Pharm.(Pharmaceutical Chemistry) 1st year.
Various organic named reactions are there in Advanced Organic Chemistry I, as some of them are explained along with their mechanism.
stereochemistry and drug action ; basic introduction about stereochemistry and stereoisomers ; pharmacokinetic and pharmacodynamics concept of stereochemistry ; easson Stedman hypothesis ; stereo selectivity criteria .
There is a trend in pharmaceutical industry towards the development of chiral drugs. Several factors have
influenced this trend in the pharmaceutical industry towards the development of the chiral drugs to provide more
potent selective and specific drugs. Over 1/3 rd of the marketed drugs worldwide are chiral and the regulators now
only will approve new chiral drugs in the single enantiomer form and even then insists on full profiling of the role
of the individual enantiomers invivo. The importance of chirality lies not only in the product development but in
the area of analytical and bioanalytical method development. Development of chiral analytical method/bioanalytical methods as per regulatory requirements requires a series of selection process to get the adequate resolution and quantification. Selection of compatible mobile phases and stationary phase that suits the particular need is very important. This presentation gives a brief description of chiral products, excipients followed by
functions and effects of its chiral forms. This presentation also describes the case studies of the chiral quantification in bioanalytical and analytical methods and their applications.
Introduction: Most of the drugs substance single enantiomer is active. In such cases the inactive enantiomer is considered as an impurity, e. g. If Dextro form is active then in this case levo form is considered as an impurity.
An enantiomer can be named by the direction in which it rotates the plane of polarized light. An optical isomer can be named by the spatial configuration of its atoms. Clockwise rotation of the light traveling toward the viewer is labelled (+) or R (in Latin Rectus for right) also termed as d-isomer i.e. dextrorotatory enantiomer. Its mirror-image is labelled (−) or S (in Latin Sinister for left) also termed as l-isomer i.e. levorotatory enantiomer.
The R / S system is an important nomenclature system for representing enantiomers. This method labels each chiral centre R or S according to a system by which its substituents are each assigned a priority, according to the Cahn–Ingold–Prelog priority rules (CIP), based on atomic number.
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Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
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1. Presenting by:
MR. PURUSHOTHAM K N
Asst. Professor
Department of
Pharmaceutical Chemistry
SACCP,B.G.Nagara
2021-2022
Stereochemistry and Drug
Action
2. • Stereochemistry mainly deals
with the spatial arrangements
of the atoms or group of
atoms in a molecules.
3. • A clear understanding of stereochemistry is
crucial for the study of complex molecules
that are biologically important e.g. Protiens,
carbohydrates, nucleic acids and drug
molecules (especially in relation to their
behavior and pharmacological actions).
4. IMPORTANT DEFINITIONS
• Isomerism refers to the phenomenon in
which more than one compounds have the
same chemical formula but different
chemical structures. And those chemical
compounds that have identical chemical
formulae but they differ in physical or
chemical properties and the arrangement of
atoms in the molecule are called isomers.
Therefore, the compounds that possess
isomerism are called “isomers”.
5. • Chirality is defined as an object or a compound which is
asymmetric and cannot be superimposed over its mirror
image (for example, our both palms) is known as ‘chiral’ or
‘stereocenter’ and this property is known as “chirality”. The
chirality is due to the three-dimensional or spatial
arrangements of the molecules and a carbon is said to be
chiral carbon when it is bonded with four different
substituents to it. The asymmetry of the molecule or
chirality is mainly responsible for the optical activity in
such organic compounds.
6. • Example: Asymmetric or chiral compounds
•A carbon within an organic
compound that contains four
different atoms or group of
atoms (substituents) bonded to it.
•A carbon with double and triple
bond cannot be considered as
asymmetric because it contain 2
and 3 total bonds respectively.
7.
8.
9. • STEREOISOMERS: Isomers that have same
molecular formula and connectivity but differ
in a way that atoms are oriented in space – i.e;
Difference between isomers lies only in 3D
arrangements of atoms.
10. • ENANTIOMER:
Greek word: enantio : opposite merons : parts
Stereoisomers with non superimposable
mirror images.
• DIASTEREOMER : Diastereomers are
stereoisomers that are not mirror images of
one another and are non-superimposable on
one another. Stereoisomers with two or more
stereocenters can be diastereomers.
11.
12. Stereoisomers
Configurational isomer :
• Geometric isomers : (a) cis & trans system
/ E & Z system
• Relative configuration / Fischer projection (
L & D configuration)
• Absolute configuration (R & S
configuration
15. R and S CONFIGURATION
• Priority of an atom is
determined by its atomic
number
• Order of substituents going
from highest to lowest
priority.
• Clockwise – R (rectus).
• Anticlockwise – S (sinister).
• Unless established
experimentally no idea
whether (+) or (-) rotation is
associated with R or S
configuration
16. Importance of the chirality in drugs
• This stereoisomerism results in different physical and
chemical properties of the compound. If this
compound happens to be drug then it results in
different pharmacokinetic and pharmaco dynamic
properties
• The importance of chiral drugs in the drug
development space cannot be understated. In
pharmaceutical industries, 56% of the drugs currently
in use are chiral molecules and 88% of the last ones are
marketed as racemates (or racemic mixtures),
consisting of an equimolar mixture of two enantiomers
17. Thalidomide-disastrous
• biological activity of the wrong
enantiomer
• In 1960 in Europe, racemic
thalidomide was given to
pregnant females to cure
morning sickness.
• This led to deformations in
babies and neurotoxic effects.
• These were due to S-
thalidomide.
• R-thalidomide contained the
desired therapeutic activity
18.
19. EXAMPLES OF CHIRAL DRUGS
• INTRAVENOUS ANAESTHETICS
• LOCAL ANAESTHETICS
• INHALATIONAL AGENTS
• NUEROMUSCULAR BLOCKING AGENTS
• SOME OTHER DRUGS
20. Intravenous anaesthetics
Etomidate
• Administered as a single isomer: R-isomer.
• Site of action: GABAA receptor.
• R-isomer is 15 times more potent than the S-isomer.
• S-isomer lacks hypnotic activity.
21. LOCAL ANAESTEHTICS
BUPIVACAINE
• Long acting local anaesthetic marketed as 50:50
racemic mixture. Reports of death due to
• Bupivacaine induced CNS toxicity and cardiotoxicity on
accidental intravenous injection and difficult
resuscitation following cardiotoxicity. Safer alternatives
• Levobupivacaine
• Ropivacaine These are S- enantiomers of bupivacaine.
• Ropivacaine is the first ‘pure’ enantiomer containing
>99% of the S-form
22. • Potential advantages of single enantiomer
products:
• Less complex, more selective
pharmacodynamic profile
• Potential for an improved therapeutic index
• Less complex pharmacokinetic profile
Reduced potential for complex drug
interactions
• Less complex relationship between plasma
concentration and effect
24. Pharmacokinetics stereoselectivity
Absorption
• Passive intestinal absorption
• Carrier transporter stereoselectivity
Distribution
• Protein binding
• Tissue distribution
Metabolism
• first pass metabolism
• Phase I and phase II metabolism
Elimination
25. Absorption and stereoselectivity
• Passive intestinal absorption For the majority of
racemic drugs, absorption appears to be by
passive diffusion , provided no stereoselectivity
26. Carrier mediated transporter
• Stereo selective
intestinal transporter
is the main cause for
marked differences in
the oral absorption of
enantiomers. L-
Methotrexate have 40
fold higher Cmax and
AUC than D-
Methotrexate
27. Distribution
Protein binding
• Stereo selective plasma protein binding could
influence distribution and elimination because
the major determinant of drug distribution and
elimination is protein binding.
• The enantiomers may display different
magnitudes of stereoselectivity between the
various proteins found in plasma
• Ex// the R- propranolol binding to albumin is
greater than S- propranolol and the opposite is
observed for 1 -acid glycoprotein.
28. R- propranolol
• Highly albumin bound
• Less potent
S- propranolol
• highly bound to AAG
available as unbound
• 40-100 time more
potent
29. • Metabolism first pass metabolism Stereo
selective drug metabolism is commonly
observed in vitro for racemic drugs and can
results in substantial differences in the vivo
plasma concentration - time profiles between
enantiomers due to stereo selective
bioavailability or drug disposition.
• some time the two isomers compete with
each other to bind the enzyme binding site,
this result in inhibition the metabolism of the
one enantiomer. Ex// propaphenone
