Steroids are a class of organic compounds that consist of four fused rings, including three six-membered rings and one five-membered ring. They are widely distributed in both animals and plants. Steroids include all sex hormones, adrenal cortical hormones, bile acids, and sterols of vertebrates. Small modifications to the molecular structure of steroids can produce significant differences in biological activity. Steroids are classified based on structural features and source. Important classes include sterols, cardiac glycosides, and sex hormones. The structures of important steroids like cholesterol, progesterone, estradiol, and testosterone were elucidated through chemical reactions and spectroscopy. Steroid nomenclature follows IUPAC rules with prefixes to

1. STEROIDS
Presented by :
Swapna. M
I M.PHARM.
DEPT. OF PHARMACHEMISTRY
SJMCP
1

2. Contents
1. General introduction
2. Chemistry
3. Stereochemistry
4. Nomenclature
5. Structure elucidation of male and female sex hormones and
contraceptive agent.
2

3. Steroid, any of a class of natural or synthetic organic compounds
characterized by a molecular structure of 17 carbon atoms arranged
in four rings. consisting of three fused six-membered and one five-
membered ring.
3

4. These are compound which are widely distributed in animals and
plant. Steroids name derived from sterol. Steroids are the
characterized by the presence of 1,2 cyclopentophenthrene.
The steroid group includes all the sex hormones adrenals cortical
hormones, bile acids, and sterols of vertebrates, as well as
the molting hormones of insects and many other physiologically
active substances of animals and plants.
4

5. Steroids vary from one another in the nature of attached groups, the
position of the groups, and the configuration of the steroid nucleus (or
gonane). Small modifications in the molecular structures of steroids can
produce remarkable differences in their biological activities.
5

6. classification
1. Sterols
the sterols, is composed of the common 3-monohydroxy steroids
of the cholestane, ergostane, and stigmastane series and their
methyl sterol biogenetic precursors.
It containing alcoholic group at C-3 position and a side chain of 8
to 10 carbon atoms at C-17 are called sterols.
Structure of sterols with carbon numbers
6

7. Sterols are classified into 3 groups based on their source of
origin. They are:
1. Zoosterols : It found in animals.
eg :- cholesterol
2. Phytosterols : It found in plants.
eg :- stigma sterols.
3. Mycosterols : it commonly found in yeast and fungi.
eg :- Ergosterols
7

8. Sterols may be found either as free sterols, acylated (sterol
esters), alkylated (steryl alkyl ethers), sulfated (sterol sulfate), or
linked to a glycoside moiety (steryl glycosides) which can be
itself acylated (acylated sterol glycosides).
8

9. 9

10. Cholesterol
It occurs both as free form or in ester form
Cholesterol has a molecular formula of C27H25OH. This molecule
is composed of three region.
• A hydrocarbon tail
• A ring structure region with4 hydrocarbon rings
• A hydroxyl group
10

11. The hydroxyl group is polar, which makes It water soluble
The 4 rings of cholesterol is the signature of all steroid hormones.
The last region is the hydrocarbon tail.
Both the ring region and tail region are non-polar
Because cholesterol contain both a water-soluble region and a fat-
soluble region, it is called amphipathic
11

12. Chemistry :
1. Presence of double bond and hydroxyl group
a. The conversion of cholesterol into cholestanol show the
presence of double bond.
12

13. b. The oxidation of cholestanol with chromic acid into
cholestanone shows the presence of secondary alcoholic group
inn cholesterol.
13

14. c. The clemmenson’s reduction of cholestanone yields a saturated
hydrocarbon called cholestane.
14

15. 2. Presence of a ring system : The molecular formula of
cholestane corresponds to the general formula CnH2n-6 of a
tetracyclic system. On distillation with selenium at 3600C,
cholesterol yields Diel’s hydrocarbon.
The reaction shows the presence of cyclopentenophenantherene
nucleus in cholesterol and thus cholesterol is a steroid.
15

16. 3. Position of the Hydroxyl group : The formation of 3,7-dimethyl
cyclopentenophenanthrene from cholesterol by the following
steps is possible only if –OH group is considered at position C-
3
16

17. Sapogenin
Sapogenins are the aglycones, or non-saccharide, portions of the
family of natural products known as saponins. Sapogenins
contain steroid or other triterpene.
Chemically they are steroidal compounds characterized by the
presence of a spiroketal side chain.
17

18. • A spiro compound is a bicyclic organic compound with rings
connected through just one atom. The rings can be different in
nature or identical. The connecting atom is also called the
spiroatom, most often a quaternary carbon
• They are derived from C27 – cholestane
• Produced from saponins by acid or enzymatic hydrolysis
18

19. • Also called tetracyclic triterpenoids
• Found in many monocotyledons such as Wild yam (Dioscorea
vilosa).
• Sapogenin – Diosgenin.
• Also found in dicotyledons fenugreek.
• Strophanthus and Digitalis contain both steroidal saponins
(glycosides) and cardiac glycosides.
• Plants of Liliaceae, Dioscoreaceae and Scrophulariaceae families.
19

20. 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
• Odourless
20

21. 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.
They exhibit λmax at 220nm.
Examples:
Digitalis glycosides:
• Digoxin
• Digitoxin
• Gitoxin
Strophanthus gratus glycoside :
• Ouabain
Strophanthus Kombe glycoside :
21

22. 2. Bufadienolide: (contain two double bonds, lactone ring):
• Has six member ( unsaturated ) lactone ring attached at C-17
alpha
–position
They exhibit λmax at 300nm.
Example:
Squill bulb glycoside
• Scillaren
22

23. Chemistry of Digitalis purpurea– purple foxglove
• Consists of the dried leaves of
“Digitalis purpurea”.
Scrophulariaceae
23

24. 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
24

25. Gitoxigenin Gitaloxigenin
Digitoxigenin
25

26. D-Digitalose D- Digitoxose
26

27. 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.
27

28. Nomenclature
Discard the names in favor of systematic names which are
approved by the international union of pure and applied
chemistry.
28

29. β configuration
Substituent attached to the ring system from above are designated
as β preferably thickened
29

30. α configuration
substitution attached to the ring system from below are
designated as α preferably brokened or dotted
30

31. Unknown configuration
• If the configuration of the substituent is not known its bond to
the nucleus is represented by a wavy line and it is indicated by
31

32. If some of the carbon atoms are missing in steroid, the
numbering of the remainder will not change in order to illustrate
the above rules
NORMAL ALTERED
32

33. If the side chain does not contain a methylene group. This is
indicated by the prefix NOR preceded by the number of carbon
atom that has disappeared
Mentioned as 21 Nor
33

34. If the steroid does not contain angular methyl group this is again
indicated by the prefix NOR preceded by the number in
designating the methyl group.
34

35. If contraction of ring of a steroid, this is again indicated by the
prefix NOR preceded by a small capital letter indicating the ring
affected
It is mentioned as A nor
35

36. If the enlargement of the ring of a steroid this is indicated by the
prefix HOMO precede by a small capital letter indicating the ring
affected
B-HOMO 5 beta pregnane
36

37. If ring fission in a steroid with the addition of a hydrogen atom
to each new terminal group, this is indicated by the numbers
showing the position of the bond broken, followed by the prefix
seco
2,3 Seco -5 β androstane 2,3 dioic acid
37

38. If steroid contain a three membered ring, this is indicated by the
prefix cyclo preceded by the number of positions concerned
38

39. When the configuration is not known for one or more
centre it is indicated by greek letter ε prefixed by the
appropriate locant [s]
39

40. If one of the bridge head hydrogen atom is replaced it may be
desirable to restate the Stereochemistry 9 α fluro, 5 α pregnane
instead of 9fluro 5 α pregnane
5 α pregnane 5 α Cholane 5 α Cholestane
40

41. Unsaturation is indicated by changing ane to ene if it contains
one double bond, diene if it contains two double bond and triene
if it has three double bond.
41

42. Naturally occuring steroids contain one or more additional
heterocyclic ring fused or attached to ring D formed by the
modification of the side chain
Cardenolide-lactone-5
member
Bufanolide – pyranone-6
member
42

43. Lengthening of side chain by insertion of one or more CH2
group indicated by prefix HOMO
43

44. Removal of terminal ring with addition of hydrogen atom at
junction where the adjacent ring is indicated by the prefix DES
followed by italic capital letter designated the ring
Des A
44

45. Alternative application of nor and homo to the same molecule
the abeo system is used
Abeo
45

46. The systematic names are based on the stem name which in turn
based on the hydrocarbon system.
Cholestane with 27 Pregnane with 21
Carbon carbon
46

47. Androstane-carbon 19
Estrane –carbon 18
Gonane – carbon 17
47

48. Stereo chemistry
The stereo chemistry of the rings markedly affects biological
activity of a given class of steroids
There are six asymmetric carbon atoms 5,8,9,10,13,14 in the
nucleus. Therefore 64 optically active forms are possible
48

49. It can exist in two conformations namely chair form and boat
form.
• Chair conformation is more stable than boat conformation due
to less angle strain.
• Hence all cyclohexane rings
• exist in chair form
49

50. 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.
50

51. 4 isomeric acids,
1. Lithobilianic acid
2. Allolithobilianic acid
3. Isolithobilianic acid
4. Alloisolithobilianic acid
51

52. Rings B/C and C/D - trans
• The configuration of 8 β and 9 α hydrogens and 14 α hydrogen
and C-18 angular methyl group denotes trans fusion for rings B/C
and C/D.
• Cis and trans relationship of the four rings may be expressed in
terms of the back bone.
52

53. 5 α cholestane have trans ,anti –trans, anti-trans back bone
Anti denotes orientation of ring that are connected to each other
and have trans type relationship
53

54. 5 β cholestane has Cis –Syn- trans-antitrans back bone in which
the A/B rings are fused Cis.
The term Syn is used in a similar fashion as anti to define a Cis
type relationship.
54

55. 55

56. 56

57. Steroid is a flat which can be explained only if the fusion ring B
and C has occurred together in trans manner.
Only trans B/C fusion takes place in natural steroid.
Ring C/D posses trans fusion.
57

58. Mostly steroids have trans C/D fusion exception in cardiac
glycoside and toad poison in which the fusion is cis. Hydrogen at
C-9 is trans to methyl group at C-10.
58

59. • The methyl groups at C-10 & C-13 are Cis
• NMR spectroscopy is quite useful in steroid chemistry.
• Angular methyl groups undergo coupling with certain protons
on the steroid nucleus.
59

60. It is also found that peak width of angular methyl group half
height for trans fused isomer is larger than that for cis fused
isomer
60

61. Configuration of hydroxyl group at C-3
• β series found in all natural steroids.
• The prefix β indicates that it lies above the plane of molecule.
• If hydroxyl group lies below the plane it gives rise to α series.
61

62. Sex steroids
Sex steroids also known gonadocorticoids and gonadal steroids,
are steroid hormones that interact with
vertebrate androgen or estrogen receptors
It was lipid soluble molecule that bind to hormone receptor in the
cytoplasm of the target cell.
62

63. SEX HORMONES
sex hormones are usually classified as follow.
i. Androgens (male sex hormones)
ii. Oestrogens (female or follicular hormones)
iii. Gestogens (corpus luteum hormones)
Andogens
It is synthesized from cholesterol in the testes and adrenal cortex
63

64. There are 4 naturally occurring androgens in man
i. Testosterone
ii. Androsterone
iii. Epiandrosterone or androstenedione
iv. Dehydroepiandrosterone or DTH
64

65. 65

66. STRUCTURAL ELUCIDATION
Testosterone exerts its physiological activity after its conversion
to dihydrotestosterone.
A steroidal skeleton is minimum structural requirement to have
androgenic activity.
66

67. • 17β hydroxyl function to be essential for androgenic and
anabolic activity.
• 1- Dehydro isomer of testosterone is a potent compound
• Reduction of the A ring may increases potency
Eg : DHT
• Introduction of 17α methyl group benefit oral activity on
testosterone.
67

68. • Testosterone not effective orally, because metabolic changes at
17β oxygen, which is used to attach the receptor site. 17α alkyl
groups prevent these metabolic changes so that compound are
orally active
Increasing the length of alkyl side chain at 17α position results
reduced activity.
68

69. • Esterification of testosterone at C-17 with a number of acid
have long duration of action when used parenterally.
• -OH group in 17α position decreases androgenic or anabolic
activity.
• Heterocyclic rings are also incorporated yield good anabolic
agent
E.g. Stanozolol
69

70. • 19 norandrogens were synthesized, some of which were found
to be effective anabolic agents.
E.g. 19- norestosrerone.
70

71. • The 3-deoxy analogs have been found to be potent androgen.
Several heterocyclic rings were then fused to ring A. the
pyrazole and isoxazole were much more active then 17α-methyl
testosterone.
71

72. FEMALE SEX HORMONES
ESTROGENS:
A group of steroid hormones that readily diffuse across the cell
membrane
Inside the cell, they interact with estrogen receptor
The estrogen are classified into three groups, they are :-
1. Natural
a. Human estrogen
E.g. estrone, estradiol, estriol.
b. Stallion estrogen
E.g. equalin, eqailenin
72

73. 2. Semisynthetic
E.g. ethinyl estradiol, mestranol, estradiol-3-propionate,
estradiol-benzoate.
3. Synthetic
E.g. dienosterol, stilbesterol, hexosterol, chlotrianisine.
73

74. 00
74

75. Structural elucidation
• Subtitution at C3 of steroidal nucleus is very essential for the
activity.
• 17β hydroxyl group at C17 position increases the duration of
action.
• Introduction of unsaturated into B-ring reduces the activity.
• Functional group at C3 and C17 are essential for activity.
• Esterification of 17 β hydroxyl and C3 hydroxyl group enhances
the oral activity and duration of action
75

76. 76

77.  17β estradiol through potent estrogen it is in activity in oral
route the –OH group at can be stabilized by introduction of 17α-
alkyl group by semisynthtic modification.
77

78. If the D ring is removed from estrone/estradiol the activity
remains same.
78

79. Progesterone
Progestin’s innclude the naturally occuring hormone
progesterone, 17 α acetoxyprogesterone derivatives in the
pregnane series.
17 α acteoxyprogesterone
79

80. 80

81. Structural elucidation
• Steroidal nucleus is essential for activity.
• Substitution at 17 α with ethynyl, methyl, ethyl reduce activity.
• Ethindrone more activity orally than progesterone.
81

82. • Removal of CH3 at C19 is more active.
E.g. norethindrone
• Unsaturation of B or C ring of 19-Androstane derivatives
increase activity.
• Acetyalation of the 17β –OH of norethindrone long duration of
action.
82

83. Hormonal contraceptives
This type is the most frequently used in the united states, which
contain both an estrogen and a progestin.
Ethiny estradiol and mestranol are the estrogens most frequently
used.
Levonorgaestrel is the most common progestin used worldwide.
83

84. Reference
1. https://www.slideshare.net/vasanramkumar/steroids-ppt
2. https://www.slideshare.net/HARISHANKARSAHU/steroids-
52790313
3. Essentials of medical pharmacology, by K.D. THRIPATHI,
6th edition, pg.no.231-307
4. Principle of medicinal chemistry, by WILLIUM O FOYE,
3rd edition, pg.no.785-795
5. Organic chemistry of natural of natural product by GURDEEP
R CHATWAL, 2nd vol.pg.no. 4.60-4.97
84

85. 85