STEROIDS

BINUJA S.S
FIRST YEAR M.PHARM
CONTENTS

 Introduction

 Stereochemistry and nomenclature of steroids

 Chemistry of cardiac glycosides and sterols

INTRODUCTION
 Large class of organic compounds.

 Nucleus-1,2 cyclopentenoperhydrophenanthrene ring.

 Includes sterols, bile acids,adreno cortical and sex

hormones
 Distilled with selenium at 360°C- DHC
 Distilled with selenium at 420°C- Crysene and picene

crysene picene
Physical properties
 Flat and rigid molecular frame work
 Highly crystalline
 Enormous number of derivatives which
have been prepared
NOMENCLATURE
 Ring were numbered and lettered
 Above the plane of the nucleus - β configuration

 Below plane of the nucleus -α configuration

 Configuration of substituents is unknown -wavy

line.

 If some carbon atoms are missing in steroid

nucleus, the numbering of the remainder will not
change.
Common examples

gonane oestrane

androstane pregnane
cholane cholestane
Other rules
1. If side chain doesn’t contain methylene group,
this is indicated by the prefix “nor”,
proceeded by the no:of carbon atom that has
disappeard.

23-nor 5α/β cholane

2. If the steroid nucleus doesn’t contain angular methyl
group, this is indicated by the prefix “nor”, proceeded
by the number that designating the methyl group.

10-nor 5α/β androstane

3. If the ring contraction occur in the steroid nucleus, this
is again indicated by the prefix “nor”, proceeded by a
capital letter indicating ring affected.

A- nor 5α/β androstane

4. If there is enlargement of ring in the steroid nucleus,
indicated by the prefix “homo”, proceeded by a capital
letter indicating ring affected.

B- homo 5 α/β pregnane

5. If there is a ring fission or breaking occurs, indicated
by the prefix “seco”, proceeded by a number of position
of bond brokened.

2,3 Seco 5α/β-androstane-2,3-dioic acid

6. If steroid nucleus contains 3 memebered ring, indicated
by prefix “cyclo”.

3α,5α-Cyclocholestane
STEREOCHEMISTRY
 Carbon atom in the steroids are numbered from 1-19 and the rings
are A,B,C,D.

 Fully saturated steroid contain 9 dissimilar asymmetric carbon

 8 in nucleus and one in the side chain(3,5,8,9,10,13,14,17 and 20).

The no:of possible optical isomers are 29=512.
 Stereoisomerism on,
 The way in which the rings are fused together.

 The way in which configuration of substituent groups,

particularly those at C3 and C17.
1. The way in which the rings are fused together.
A/B FUSION
Fusion of rings A and B may either trans or cis to give 2
isomeric (allo and normal) C27hydrocarbon.
4 isomeric acids,
1. Lithobilianic acid
2. Allolithobilianic acid
3. Isolithobilianic acid
4. Alloisolithobilianic acid
 ‘R’ is CHCH3(CH2)2COOH.

 When all the 4 acids heated,

B/C FUSION
 Fusion of the rings B and C was trans.

 The C10 angular methyl group must be trans to the C9

hydrogen atom.

 Confirmed by the complete X-ray crystallographic

analysis of cholesteryl iodide.
C/D FUSION
The complete X-ray crystallographic analysis of
cholesteryl iodide reveals that the ring union is trans in the
sterols, bile acids and related steroids.
THE SIDECHAIN

 If the side chain becomes involved in heterocyclic structures

geometrical isomerism may appear at C20 ,C22 and C25.

 Stereoisomerism of the classical tartaric acid type involving

free rotation.

 However occurs generally at the asymmetry centre at C20 and

may occur at C24 , when substitution of hydrogen by a –CH3
or -C2H5 leads to asymmetry.
CHEMISTRY OF STEROL
 Steroid alcohol.
 Occur naturally in plants, animals and fungi.
 Cholesterol. - crystalline compounds containing a 2̊ alcoholic
group.
 3 types

1. Zoosterol – cholesterol, cholestanol,coprosterol

2. Phytosterols-campesterol,sitosterol,stigmasterol,
ergosterol
3. Mycosterol - ergosterol, vitamin D
 Sterol chemical structure

Chemistry of sterol is explained by using

cholesterol structure.
•M.F: C27H45OH.
•SOURCES : Cholesterol was isolated from human gall
stones, fishliver oils and brain and the spinal cord of
cattle, Lanoline, the fat from wool, consists of a mixture
of cholesteryl palmittate, stearate and oleate.
 3 three regions

1. A hydrocarbon tail

2. A ring structure region with 4 hydrocarbon rings

3. A hydroxyl group
CHEMISTRY OF CARDIAC
GYCOSIDES
 A substance which on hydrolysis yields a
sugar part & non-sugar substances
(genin/aglycone) linked by glycosidic
bond.
Eg: Cardiac glycosides, flavonoid
glycosides,
phenolic glycosides etc.
Cardiac glycosides
 Group of steroidal glycosides act as cardiotonic agent.
 They increase tone, excitability and contractility of cardiac muscles.
General properties of Cardiac Glycosides :
 Amorphous powder
 Bitter taste
 Solubility in H2O
 Insolubility in Organic solvents
 Very toxic compounds
 Odorless
 Enzyme hydrolysis → glycon and aglycon

 1. Cardenolide (one double bond, lactone ring) :

Has five member lactone ring (unsaturated) attached at C-17 position

of steroidal nucleus.

Examples:

Digitalis glycosides:

 Digoxin

 Digitoxin

 Gitoxin

Strophanthus gratus glycoside :

 Ouabain

Strophanthus Kombe glycoside :

2. Bufadienolide: (contain two double bonds, lactone ring):
 Has six member ( unsaturated ) lactone ring attached at C-17 alpha
–position

Example:

Squill bulb glycoside

 Scillaren
General structure
Cardenolides
 Chemistry of Digitalis purpurea
– purple foxglove

• Consists of the dried leaves of

Digitalis purpurea.
Scrophulariaceae
Hydrolysis reaction

 Purpurea glycosides A → digitoxin + glucose

 Digitoxin → Digitoxigenin + 3 molecules of digitoxose

 Purpurea glycosides B→ gitoxin + glucose

 Gitoxin → Gitoxigenin + 3 molecules of digitoxose

 Verodoxin → Gitaloxigenin + 1 molecule of digitalose

 Gitaloxigenin
Gitoxigenin

Digitoxigenin
D-Digitalose
D- Digitoxose
 C23 steroid because of 5 membered lactone.

 Sugar portion is attached through C3- β linkage and

Digitalis purpurea contains 3 sugar molecule are
attached to the aglycone. They are digitoxose and
digitalose.

 Active glycoside of Digitalis purpurea contain a

‘OH’group at C3 and C14.
CHEMICAL TESTS
 Salkowski reaction
 Baljet test
 Legal test
 Keller kiliani test for deoxy sugars
USES
◦ Conjestive heart failure
◦ Improve circulation,venous circulation which reliefs
the oedema associated with heart failure.
 Chemistry of Digitalis lanata

•consists of dried leaves of

Digitalis lanata, family
Scrophulariaceae
Chemical constituents:
• lanatosides A,B,C and E.
•Lanatoside A and B are acetyl
derivatives of purpuryl glycosides
respectively.
•The acetyl group is attached to
terminal digitoxose sugar.
 Lanatoside C →Digoxin + acetic acid + glucose

Lanatoside E → Gitatoxin + acetic

acid+ glucose
 Chemistry of Strophanthus
•Consists of dried ripe fruits of
Strophanthus combe, family
Apocyanaceae.
Chemical constituents:
•consists of 8-10% cardiac
glycosides called as K-
Strophanthidin which is a mixture
of 3 glycosides namely
1. Cymarin,
2. K- Strophanthin β
3. K-Strophanthoside
 Strophanthidin
Chemistry of Ouabain
 A cardiac glycoside obtained from the seeds of
Strophanthus gratus or from the woods of Akokanthra
schimperi, family Apocyanaceae.

 more potent than K-Strophanthin.

G-Strophanthin
Bufadienolides
SQUILL(SCILLA)
 consists of dried slices of bulbs of Urgenia indica
(Indian squill), Urgenia maritima(European squill)
family Liliaceae.

Chemical constituents:

 Scillaren A and Scillaren B.

 Scillaren A mainly responsible for cardiac activity of the

drug.
 ScillareninA → biglycoside(containing 2 sugars-
glucose and rhamnose).

 Aglycone portion is Scillarenin A or otherwise called

Scillaridin.

Scillaren A
Scillarenin A + scillabiose+ rhamnose+ glucose
USE
 As a cardiotonic without cumulative effect.

 Used in chronic bronchitis

 Expectorant in small doses

 In high dose causes emesis

 Also causes diuretic property.

REFERENCE

 Organic chemistry of natural products by

Gurdeep.R.Chatwal

 Volume-2 page.no: 347-359, 405-409.

 Pharmacognosy by C.K.Kokate,A.P.Purohit,
S.B.Gokhale volume 1and 2, 47th edition.

 https://en.wikipedia.org/wiki/natural product

 https://en.wikipedia.org/wiki/cardiac glycosides
 www.slideshare.net.in

 www.organicchemistry.org/books/navi/natural
products.shtm

 Chemistry.tutorista.com/biochemistry

 https://en.wikipedia.org/wiki/cholesterol

 www.cholesterol-and-health.com/cholesterol
hydroxyl.html.