Steroids

STEROIDS
CHOLESTEROL
Presented To:- Presented By:-
Dr. KASHIF YOUNIS BUTT SHEHMAN ASAD
Department of Chemistry, 15301507-042
GOVT.MURRAY COLLEGE. BS(CHEM) VIII-Sem

STEROIDS
 Steroids comprise a group of cyclical organic compounds whose basis is a
characteristic arrangement of seventeen carbon atoms in a four ring structure linked
together from three 6-carbon rings followed by a 5-carbon ring and an eight-carbon
side chain on carbon-17.
 A group of structurally related compounds which are widely distributed in animals
and plants.
 Steroids possess a common structure –
PERHYDROCYCLOPENTANOPHENANTHRENE Nucleus.
 Includes Cholesterol, bile acids, androgens, adrenocortical, adrenomedullary,
estrogenic, and progestational hormones.
 Two principal biological functions:
• Alter membrane fluidity
• As a signaling molecules
1

STRUCTURE OF STEROID
 BASIC CORE STRUCTURE:
o 17 Carbon Atoms bonded in four “fused” rings
o 3 six-membered cyclohexane rings
o 1 five-membered cyclopentane ring
2

STRUCTURE OF STEROIDS
 Rosenheim and King (1932); Wieland and Dane (1932) proposed that the structure
of steroids are based on the 1:2-cyclopentenophenanthrene skeleton.
3

CHOLESTEROL
 Originated from Greek word “Khole” meaning ‘Bile’ + “Stereos” meaning ‘Stiff’ + -ol
in late 19th century.
 Lipidic and waxy alcohol found in the cell membranes and transported in
the blood plasma of all animals.
 Essential component of mammalian cell membranes where it is required to
establish proper membrane permeability and fluidity.
 Principal sterol synthesized by animals, but small quantities are
synthesized in other eukaryotes, such as plants and fungi.
 Cholesterol is classified as a sterol (contraction of steroid and alcohol).
4

CHOLESTEROL
 80% made from liver
 20% made from diet
 80% of your brain
 20% of every cell wall
 100% of your far based hormones like
 Vitamin D , Progesterone, Estrone, Cortisol,
Testosterone, etc….
 Present in tissues and in plasma either as free cholesterol
or as a storage form, combined with a long chain fatty acid.
5

STRUCTURE OF CHOLESTEROL
 The structure of cholesterol consists of four fused rings with carbons numbered in
sequence, and an eight numbered branched hydrocarbon chain.
 Contains two angular methyl groups: the C-19 methyl group is attached to C-10, and
the C-18 methyl group is attached to C-13.
 The C-18 and C-19 methyl groups of cholesterol lie above the plane containing the
four rings.
6

STRUCTURE OF CHOLESTEROL
 Steroids with 8 to 10 carbon atoms in the side chain and an alcohol hydroxyl group
at C-13 are classified as sterols.
 Much of the plasma cholesterol is in the esterified form (with the fatty acid
attached at Carbon-3), which makes the structure even more hydrophobic.
7

PROPERTIES OF CHOLESEROL
Molecular Formula C27H46O
Molar Mass 386.65 g/mol
Appearance White Crystalline powder
Density 1.052 g/cm3
Melting Point 148-150ºC
Boiling Point 360ºC (decomposes)
Soulubility in water 0.095 mg/L
Solubility Soluble in organic solvents
8

CHEMICAL PROPERTIES
 Undergoes rapid oxidation to form cholestenones.
 Hydroxyl group forms esters with acids to form Cholesterol Esters (cholesterol
acetate, palmitate and propionates).
 Presence of double bond gives hydrogenation reactions (similar to unsaturated
fatty acids).
 Colour Reactions: Liebermann-Burchard, Salkowsky, Zaks.
 Intestinal bacteria reduce cholesterol into coprosterol and dihydrocholesterol.
9

COLOUR REACTIONS
 The SALKOWSKI Reaction (1908):
Concentrated Sulphuric Acid is added to a solution of cholesterol in chloroform, a
red colour is produced in the chloroform layer.
 The LIEBERMANN-BURCHARD Reaction (1885,1890):
A greenish colour is developed when a solution of cholesterol in chloroform is
treated with conc. Sulphuric acid and acetic anhydride.
 The ZAKS Method Reaction:
Proteins present in serum sample are first precipitated by adding FeCl3-CH3COOH
reagent. The protein free filtrate is treated with conc. Sulfuric acid. In the presence
of conc. Sulfuric acid, cholesterol present in serum gets dehydrated to form
cholesterol-3,5-diene in presence of excess sulfuric acid and a red coloured
complex is formed.
10

STRUCTURAL ELUCIDATION
STRUCTURE OF NUCLEUS
۩Molecular formulae: C27H46O.
۩Forms mono acetate on acetylation indicating one hydroxyl group.
۩It adds 2 bromine atoms forming cholesterol dibromide indicating presence of one
double bond.
۩A to B proves presence of double bond.
۩B to C shows presence of secondary alcohol.
cholesterol
H2-Pt
cholestanol cholestanone cholestane
CrO3 Zn-Hg/ Hcl
(C27H480) (C27H46O) (C27H48)
(C27H460)
A B C D
11

STRUCTURE OF NUCLEUS
۩The saturated parent hydrocarbon D of cholesterol corresponds to general formulae
(CnH2n-6) for tetra cyclic compounds hence it is tetra cyclic alcohol.
Total no. of rings is given by: (No. of carbons + 1 ─ no. of hydrogen / 2)
۩On selenium distillation at 360oC, cholesterol gives diel’s hydrocarbon and chrysene,
the formation of diel’s hydrocarbon suggests that cholesterol has diel’s hydrocarbon
nucleus in its structure.
HO
H
H
H
cholesterol
CH3
Se
360o
diels hydrocarbons
12

Position of hydroxyl group and double bond:
۩ Cholestanone on oxidation with nitric acid gives a dicarboxylic acid which on
pyrolysis yields a ketone.
cholesterol
H2-Pt
cholestanol cholestanone cholestane
CrO3 Zn-Hg/ Hcl
(C27H480) (C27H46O) (C27H48)
(C27H460)
HNO3
pyrolysis
360
0
two isomeric dicarboxylic acids
(C27H46O4)
ketone
13

From the previous reactions the following reactions are concluded:
۩ The oxidation of Cholestanone to dicarboxylic acid having same no. of carbon
atoms as original ketone indicates that keto group must be present in the ring. If in the
side chain it gives acid with less no. of carbon atoms.
۩ pyrolysis of dicarboxylic acid to ketone with less no. of carbon atoms reveals that
dicarboxylic acid is 1,6 or 1,7 dicarboxylic acid (blancs rule).
۩ But opening of ring to yield dicarboxylic acid occurs due to hydroxyl group so that
hydroxyl group not in the ring D if it is in the ring D then it gives 1,5 dicarboxylic acid,
so hydroxyl group is in ring A.
۩ When cholestanone is oxidized actually 2 isomeric dicarboxylic acids are obtained
which indicates that keto group is flanked on either side by methylene group so that
CH2-CO-CH2.
14

When cholestanone is oxidized actually 2 isomeric dicarboxylic acids are obtained
which indicates that keto group is flanked on either side by methylene group so that
CH2-CO-CH2.
۩
COOH
HOOC
HOOC
HOOC
O
-OH AT 3
HNO3
15

O
HOOC
HOOC
HOOC
COOH
-OH AT 2
HNO3
If proposed structure for cholesterol is examined such an arrangement is only
possible if hydroxyl group is present in ring A.
16

۩ The position of hydroxyl group at position 3 is further confirmed by following
reactions:
HO
H
H
H
CHOLESTEROL
HO
H
H
H
cholestanol
H
H
H
O cholestanone
CH3
diels hydrocarbons
H3C
Se
360
o
HO
CH3
CH3MgI
The given reaction is formulated as
follows if hydroxyl group is present in
position 3 which corresponds with the
position 7 in 3,7-dimethyl
cyclopentenophenanthrene.
17

Position of double bond
cholesterol cholestanetriol hydroxycholestanedione
cholestanedione
pyridazine derivative
tetracarboxylic acid
H2O2/ACOh CrO3
---H2O
Zn-CH3COOH
CrO3
NH2NH2
C27H46O
C27H48O3 C27H44O3
C27H44O2
C27H4408
A B C
E
D
From the above reactions the following reactions are concluded:
۩The conversion of A to B represents the hydroxylation of
double bond.
۩ B on oxidation gives a diketone indicating that in B two
of OH groups are secondary in nature and third is tertiary
one (which resists oxidation).
18

۩ Since D can form a pyridazine derivative with hydrazine the two ketonic groups of D
are in γ position with respect to each other which is only possible only if double bond
is present in between C5 and C6 and all previous reactions are written as:
O
O
O
O
H
N
N
H
COOH
COOH
HOOC
HOOC
HO
OH
OH
HO
OH
O
O
A B C
D
E
19

SYNTHESIS OF CHOLESTEROL
 Sir R. Robinson et al. (1951) and Woodward et al. (1951) have synthesized
cholesterol.
 Major Difficulty in the synthesis is the stereochemical problem.
 Every step in the synthesis which produced a new stereogenic center had to result
in the formation of some (the more the better) of the desired stereoisomer.
 Eight asymmetrical Carbon atoms and 256 optical isomers.
 Another difficulty was attacking a particular point in the molecule without
affecting other parts.
 This problem leads to the development of specific reagents.
20

WOODWARD SYNTHESIS
Generation of Precursor molecule
4-Methoxy-2:5-toluquinone was prepared from 2-methoxy-p-cresol by the series of
reactions.
21

WOODWARD SYNTHESIS
ROAD TO CHOLESTEROL
STEP 1: DIELS ALDER REACTION
STEP 2: ISOMERIZATION TO TRANS-FORM
22

WOODWARD SYNTHESIS
STEP 3: REDUCTION
STEP 4: ACIDIFICATION
23

WOODWARD SYNTHESIS
STEP 5: ACETYLATION followed by reduction with metal and acid
STEP 6: CLAISEN CONDENSATION
24

WOODWARD SYNTHESIS
STEP 7: MICHEAL CONDENSATION
STEP 8: CYCLIZATION
25

WOODWARD SYNTHESIS
STEP 9: HYDROXYLATION
STEP 10: TREATMENT WITH ACETONE
26

WOODWARD SYNTHESIS
STEP 11: CATALYTIC REDUCTION
STEP 12: CLAISEN CONDENSATION + TRREATMENT WITH METHYL ANILINE
27

WOODWARD SYNTHESIS
STEP 13: CONDENSATION WITH VINYL CYANIDE & HYROLYSIS
STEP 14: TREATMENT WITH ACID ANHYDRIDE AND GRIGNARD REAGENT
28

WOODWARD SYNTHESIS
STEP 15: RING CLOSURE & Oxidation with periodic acid
STEP 16: Heat in Benzene Solution with piperidine acetate in aq. dioxan
29

WOODWARD SYNTHESIS
STEP 17: OXIDATION
STEP 18: REDUCTION & OPPENAUER OXIDATION
30

WOODWARD SYNTHESIS
STEP 19: REDUCTION
STEP 20: Reaction with acid anhydride & Grignard Reagent
31

WOODWARD SYNTHESIS
STEP 21: DEHYDRATION
STEP 22: REDUCTION & Reaction with sodium dichromate
32

WOODWARD SYNTHESIS
STEP 23: BROMINATION
STEP 24: REDUCTION followed by REACTION with ACETYL CHLORIDE
33

Steroids

More Related Content

What's hot

Similar to Steroids

Recently uploaded

Steroids