1-Show how the nature and position of the side chain in cholesterol were elucidated

Answer:

A. Nature of the side chain:

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

• This indicates that isopropyl group is directly attached to 3 methylene groups. (

Isopropyl-CH2-CH2-CH2-)

• This indicates that there is an alkyl group on the α-carbon atom in bisnor-5-β-
cholanic acid.

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

• 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

B- Position of the side chain:

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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.

2-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:

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 - 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 Oxidation 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.

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 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

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

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

I-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

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

This is In accordance with a homoannular diene rather than heteroannular diene -

 So, the two double bonds present in one ring.

Ergosterol: C28H44O

iii- 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

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iv- 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

4- Complete the following equations:

U.V
- Ergosterol …………

H H
HO h

Ergosterol H

H
HO (1,7) H-shift

H
7
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
8
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

5- 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

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  Dehydroepiandrosterone

6- What are the parent names of steroids with the following C-skeletons?

C-27 skeleton C-24 skeleton C-21 skeleton

Cholestanes Cholanes Pregnanes

C-18 skeleton C-19 skeleton

Estranes Androstanes
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Draw the most likely feasible conformational isomers of Steroid -7

8- Write the structural formula of each of the following compounds

R
R CH3
CH3

CH3
CH3

H H

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

3α-hydroxy-5α-androstan-17-one
Androsterone

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 CH2OH
C O
OH O
O

O HO

Cortisone Oestrone

H H
O
Progesterone

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