Show how the nature and position of the side chain in cholesterol

were elucidated

Answer:

Nature of the side chain:

CrO3
C O +

5 ß- Cholestane 5 ß- Cholanic acid

(I) (II)
• This indicates that the side chain in β- Cholestane (and also
Cholesterol) ends with isopropyl group.

COO
H
COOH
B.W. B.W.

nor-5 ß- Cholanic acid bisnor-5 ß- Cholanic acid

5 ß- Cholanic acid
(II) (III) (IV)

• This indicates that isopropyl group is directly attached to 3

methylene groups. ( Isopropyl-CH2-CH2-CH2-)

B.W.

bisnor-5 ß- Cholanic acid Etiocholyl methyl ketone

(IV) (V)

• This indicates that there is an alkyl group on the α-carbon atom in

bisnor-5-β-Cholanic acid.
 O COOH
CrO3

Etiocholyl methyl ketone Etianic acid

(V) (VI)

• Oxidation of ketone (V) to an acid (VI) with the loss of one carbon
atom indicates that the ketone must be methyl ketone.

COOH O
B.W. HNO3 COOH
COOH

Etianic acid Etiocholanone Etiobilianic acid

(VI) (VII) (VIII)
• Formation of Etiocholanone and hence Etiobilianic acid with the
same number of carbon atoms indicates that:

 The ketone should be cyclic ketone

 There are 8 carbons in the side chain in the following arrangement

Position of the side chain:

CH3
O
COOH Ac2O O Se CH3
COOH -H2O
O
Etiobilianic acid Etiobilianic acid anhydride 1,2- Dimethylphenanthrene
(VIII) (IX) (X)
Heating the dicarboxylic acid (VIII) with Ac2O gives Anhydride, So

• The ketone (VII) is a five membered ring ketone ( in accordance

with Blanc’s rule

• The side chain is attached to the five membered ring D

- Formation of (X)as a result of distilling the anhydride with Se is a proof

for the presence of the phenanthrene nucleus in Cholesterol

Conversion of Cholesterol to Diel’s hydrocarbon suggests that the side

chain is at position 17, since Se dehydrogenation may degrade a side
chain to a methyl group.

Explain and illustrate with equations and structures what does each
of the following statements mean?

- Oppenauer Oxidation Of Ergosterol yields a product with λmax

235
 This is similar to α,β- unsaturated ketone and this indicates that one of
the double bonds in 5,6- position and moves to 4,5- position during
oxidation.
H
H

H H Oppenauer Oxid. H H
HO O
Ergosterol  Unsaturated ketone
.Ergosterol has an absorption maximum at 282 nm -

This is In accordance with a homoannular diene rather than -

.heteroannular diene i.e., the two double bonds present in one ring

Ergosterol: C28H44O

- Ozonolysis of Ergosterol gives, among other products, methyl

isopropyl acetaldehyde
21 28
22 H
20 25 27 O
24
23
O
26
O3 + H
methyl isopropyl acetaldehyde

 This proves that a methyl group at C24 and unsaturation between C22 &
C23
 Formation of 3’,7-dimethyl cyclopentanophenanthrene from
cholesterol by the following steps:
i- Catalytic reduction by using H2/Pt
ii- Oxidation with CrO3
iii- Reaction with CH3MgBr
iv- Distillation with Se at 350 0C

H2 / Pt CrO3

HO HO O
H H

CH3MgBr
CH3
3'
Se
350 oC
H3C
H3C 7 HO H
3',7-Dimethylcyclopentanophenanthrene
This is possible only if –OH group in Cholesterol is considered at
position C-3

Write the structural formula of each of the following compounds

R
CH3
R
CH3

CH3
CH3

H
H

HO H
HO H
5α- cholestane - 3β- ol 5β- cholestane - 3β- ol
Cholestanol R Coprostanol R
CH3 CH3

CH3 CH3

H H

HO H HO H
 5α- cholestane -3α - ol 5β- cholestane - 3α- ol
Epicholestanol Epicoprostanol
R
CH3

CH3

O
Cholest-4-en-3-one

CH2OH
3α-hydroxy-5α-androstan-17-one
C O
OH Androsterone
O

O
Cortisone
 O

H H
O
Progesterone

Draw the most likely feasible conformational isomers of Steroids

What are the parent names of steroids with the following C-

skeletons?
C-27 skeleton C-24 skeleton C-21 skeleton
Cholestanes Cholanes Pregnanes

Complete the following equations:

U.V
- Ergosterol …………

H H
HO h

Ergosterol H

H
HO (1,7) H-shift

H
HO
Ergocaciferol
Vit B2
Etiobilianic acid
Ac2O ....................... Se .......................
-H2O

CH3
O
COOH Ac2O O Se CH3
COOH -H2O
O
Etiobilianic acid Etiobilianic acid anhydride 1,2- Dimethylphenanthrene

i- CrO3
5cholystanyl 3acetate ................
ii- hydrolysis

H H
i- CrO3
H H ii- hydrolysis H H
AcO HO
H H
5cholystanyl 3acetate Epiandrosterone

Oxidation
Testosterone

OH O

H H

H H Oxidation H H

O O
Testosterone Androst-4-ene-3,17-dione

Two successive Barbier-Wieland degradations on nor-5β- cholanic acid

 COO O
H
COOH
B.W. B.W.

nor-5 ß- Cholanic acid bisnor-5 ß- Cholanic acid Etiocholyl methyl ketone

Starting from cholesterol show how you could prepare:

 5β-Cholanic acid

CH3 CH3

Oppenauer Oxid. H2/Pt

[(CH3)CO]3Al
HO O
Cholesterol Cholest-4-en-3-one

CH3
CH3

i- Oxid. CrO3 CrO3

HO ii- Clemenson
H reduction
H
Coprostanol
Coprostane
CH3 CO2H

CH3

H
5Cholanic acid

 Dehydroepiandrosterone
Show how the positions of the double bonds in Ergosterol were
elucidated

 Ozonolysis of Ergosterol gives, among other products, methyl

isopropyl acetaldehyde which proves that:
- The side chain must contain only one double bond
- One of the double bonds is located between C22 & C23
21 28
22 H
20 25 27 O
24
23
O
26
O3 + H
methyl isopropyl acetaldehyde

 When heated with maleic anhydride, Ergosterol forms an adduct

- So, two of the double bonds are conjugated.
 Ergosterol has an absorption maximum at 282 nm. In accordance with
a homoannular diene rather than heteroannular diene
 - Two double bonds present in one ring.

 Oppenauer Oxidn. Of ergosterol yields a product with λmax 235, similar

to α,β- unsaturated ketone
- One of the double bonds in 5,6- position and moves to 4,5-
position during oxidation.

PhCO3H i- H2/Pt
H H H
HO HO ii- OH-
OH HO OH
Ergosterol OCOPh OH

 Oxidation of ergosterol with perbenzoic acid gives the monobenzoate

of triol which on catalytic hydrogenation followed by hydrolysis gave
a saturated triol.
 This saturated triol
- when treated with lead tetra-acetate underwent fission, hence, 2 –
OH groups must be vicinal
- When treated with acetic anhydride form only a diacetate, hence
one –OH must be 3ry

H
H

H H Oppenauer Oxid. H H
HO O
Ergosterol  Unsaturated ketone
These results are readily explained on the bases that one double bond is
in the 5,6- position and the other in 7,8- position