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STEROIDS
A PRESENTATION BYARGHA SEN
B.PHARM(3RD YEAR)ROLL NO.-19301910036REG. NO.-101930210006
DONE UNDER THE GUIDANCE OF Dr. JAYANTA CHATTERJEE
INTRODUCTION•Steroids are members of a large class of organic compounds occurring mostly in plants and animals.
•Steroids are characterized by the presence of 1,2 -cyclopentanophenanthrene nucleus in their structure.
Sources of SteroidsVitamin DBile acidsAdrenal Cortex and Sex HormonesCardioactive LactonesSapogeninsCertain alkaloids and antibiotics
Definition of SteroidsSteroids are compounds possessing the
skeleton of cyclopenta[α]phenanthrene or a skeleton derived there from by one or more bond scissions or ring expansions or contractions.
Steroids can also be defined as compounds which yields Diel’s hydrocarbon when distilled with Selenium 360 degree Celsius.
Properties of SteroidsThey have relatively flat and rigid
molecular framework.They have high crystalline properties.Enormous number of derivatives have
been produced.They are both hydrophobic and
lipophilic. They contain no fatty acidsCholesterol is the best known steroid,
occurs exclusively in animals.
Nomenclature of Steroids
There are four steroid skeletons present in the steroidal drugs; the gonane skeleton, the estrane skeleton, the androstane skeleton, and the pregnane skeleton.
The gonane skeleton is the simplest one. The C19 methyl group at C10 and the C18 methyl group at C13 are absent in this skeleton.
In estrane only the methyl group at C10 is missing.
In the androstane skeleton, both the methyl groups at the C10 and C13 positions are present.
In pregnane, an additional ethyl group in the β-position at C17 is present.
13
149
810
1712
11
15
16
75
6
H
H1
4
2
3
H
H
H
H
13
149
810
1712
11
15
16
75
6
CH318
CH319
1
4
2
3
H
H
H
H
13
149
810
1712
11
15
16
75
6
H1
4
2
3
H
H
H
H
13
149
810
1712
11
15
16
75
6
CH318
CH319
1
4
2
3
H
H
H
20 CH321
H
5-α- gonane
5-α- estrane
5-α- androstane
Pregnane
Stereochemistry of Steroids 8 dissimilar chiral centers. Number of possible isomers is 256. If the chiral center at C-20 was taken into
consideration then number of isomers would be 512.
Stereochemistry of Steroids
When the H-atom at C-5 is pointing towards the bottom side( i.e. it lies below the plane) it is indicated by 5α and it will be drawn by a hatched bond in the formula.
When the H-atom at C-5 is pointing towards the top side( i.e. it lies above the plane) it is indicated by 5β and it will be drawn by a thick wedge-shaped bond in the formula.
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17
12
11
15
16
75
6
20CH318
CH319
1
23
22
4
CH321
24
2
3
H
H
H
H25
CH327
CH326
H
13
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810
17
12
11
15
16
75
6
20CH318
CH319
1
23
22
4
CH321
24
2
3
H
H
H
H25
CH327
CH326
H
5β-cholestane
(Coprostane) 5α-cholestane
Stereochemistry of Steroids All naturally occurring steroids have either
‘cholestane’ or ‘coprostane’ configuration. In cholestane, the A and B rings, B & C rings , C & D
rings are in ‘trans’ configuration respectively. In coprostane, the A and B rings are in ‘cis’
configuration & B & C rings , C & D rings are in ‘trans’ configuration respectively.H
H
A B
H
HA B
Stereochemistry of Steroids Three dimensional structure of three most
common isomersCH3 H
HH
CH3
H
R
H
CH3 H
HH
CH3
H
R
H
trans-trans-transcis-trans-trans
CH3 H
HH
H
CH3R
H
cis-trans-cis
IDENTIFICATION OF STEROIDS
Steroids can be identified by one of the following methods:
1) Fourier transform Infrared spectroscopy(FT-IR), Gas Chromatography, Fourier transform Nuclear Magnetic Resonance (FT-NMR), TLC.
2) Four spot tests are performed: with sulphuric acid, napthol-sulphuric acid, Libermann & Buchard’s Test.
3) In Libermann and Buchard test steroid is reacted with acetic anhydride & H2SO4 which leads to the formation of a blue-green complex.
Biosynthesis of steroids
13
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17
1211
15
16
75
6
20CH318
CH319
1
22
4
2
3H
H
H
H
OH H OH
OHCH3
O
OH
13
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810
17
12
11
15
16
75
6
20CH318
CH319
1
23
22
4
24
2
3H
H
H
H25
CH327
CH326
OH
CH3
13
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810
17
12
11
15
16
75
6
20CH318
CH319
1
CH322
4
2
3H
H
H
H
OH
O
13
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810
17
12
11
15
16
75
6
20CH318
CH319
1
CH322
4
2
3H
H
H
H
O
O
13
149
810
17
12
11
15
16
75
6
20CH318
CH319
1
22
4
2
3H
H
H
OH
O
O
OH
OH
13
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810
1712
11
15
16
75
6
OH20CH3
18
CH319
1
4
2
3H
H
H
O
13
149
810
1712
11
15
16
75
6
OH20CH3
18
1
4
2
3H
H
H
OH
13
149
810
1712
11
15
16
75
6
OH20CH3
18
1
4
2
3H
H
H
OH
OH
Aromatase
Pregnenolone
Cholesterol
Metabolism
Cholic Acid
Cortisol
Progesterone
Testosterone
Estradiol
16-α-hydroxylaseEstriol
Classification of SteroidsSTEROLS.GLUCOCORTICOIDS(GC’s):
Hydrocortisone, 11-Dehydrocorticosterone, Corticosterone.
MINERALOCOTICOIDS(MC’s): Aldeosterone, 11-Deoxy-corticosterone, 11-Deoxy-17-oxy-corticosterone.
CARDIAC GLYCOSIDES: Digitoxin, Digoxin. SEX HORMOMES:
1. MALE SEX HORMONES: Androsterone, Androstendion.
2. FEMALE SEX HORMONES: Oestrone, Progesterone.
Sterols Sterols are steroids carrying hydroxyl group at C-3
and most of the skeleton of cholestane. In most naturally occurring sterols the hydroxyl group at C-3 is in β-configuration(cis) i.e. it lies above the plane of the ring. E.g. cholesterol, ergosterol etc..
13
149
810
17
12
11
15
16
75
6
20CH318
CH319
1
23
22
4
CH321
24
2
3H
H
H
H25
CH327
CH326
OH
H
HCholesterol
( cholest-5-en-3β-ol)
HORMONE SOURCE PHYSIOLOGICAL ACTION
THERAPEUTIC ACTION/USE
ANDROGENNATURAL:testosterone
Leydig cells of testis
Development and maitenance of masculine characteristics and secondary male sex characters
Parenteral:•testosterone•Testosterone propionate/ethanoate/cypionate
OTHER ANDROGENS
Oral:•Methyl testosterone•Danazole
Androsterone Byproduct of androgen breakdown, or derived from progesterone
Has some masculinising effects
Nandrolone
DHT(Dihydro-testosterone)
Metabolite of testosterone
More potent than testosterone as it binds more strongly to androgen receptors.
Androstanedione
Testis, adrenal cortex, ovaries
Metabolically converted to testosterone & other androgens.
BANNED BY IOC
Androstanediol
Steroidal metabolite
Main regulator of gonadotropin secretion
DHEA(dehydroepiandrosterone)
From Cholesterol in Adrenal cortex
Precursor of natural estrogens
Androgens( S.A.R.)
1)Esterification of 17-β hydroxyl group with carboxyl decreases polarity , and increases lipid solubility which in turn causes prolonged action.2)Alkylation of C-17 position (17-α) allows androgen to be effective orally as they are slowly catabolised by liver.
CH3
CH3
H
H
H
OH
O
C H 3M gB r
CH3
CH3
H
H
H
OH
OH
CH3
O p p an eu e r O x id a tion
CH3
CH3
H
H
H
O
OH
CH3
CH3
CH3
H
H
H
OH
OH
CH
O p p an eu e r O x id a tion
CH3
CH3
H
H
H
O
OH
CH
H C O O C 2H 5
C H 3O N a
CH3
CH3
H
H
H
O
OH
CHOH
N H 2O H
CH3
CH3
H
H
H
O
OH
CH
N
Dehydroepiandrostane
Lithium acetylide
17- Methyl Testosterone
DANAZOL
Synthesis of Various Synthetic Androgens
HORMONE SOURCE PHYSIOLOGICAL ACTION
THERAPEUTIC ACTION/USE
OESTROGEN Ovaries, follicles, Corpus leuteum, placenta
Found both in men and women.1)Development of secondary sexual characters in female
Oral contraceptives.Hormone receptor positive cancer(treated with estrogen receptor blocker)
NON-STEROIDAL(SYNTHETIC:Diethylstilbestrol
Secondary source: liver, adrenal glands
2) Regulate menstrual cycle
Ethinyl estradiol & Mestranol(prodrug)
Demethylation in liver
STEROIDAL
Oestrone Diethylstilbestrol
Oestriol
Oestradiol
Oestrogens( S.A.R.)
1)In 17-β oestradiol,oestrone,oestriol the ethynyl group at C-17 greatly increases oral potency.2)Esters get absorbed more slowly.
Synthesis of DiethylstilbestrolO CH3
O
O CH3
O CH3
O
O CH3
CH3
O CH3
O CH3
CH3 OHCH3
OH
OH
CH3
CH3
1,2-bis(4-methoxyphenyl)ethanoate
Ketone
Carbinol
Diethylstilbestrol(trans-α,β-Diethyl-4,4’-stilbendiol)
C2H5IC2H5ONa
C2H5MgBr
p-toluenesulphonic acidKOH
HORMONE SOURCE PHYSIOLOGICAL ACTION
THERAPEUTIC ACTION/USE
PROGESTERONE(C-21) STEROID HORMONE.
Ovary, adrenal gland, corpus luteum, placenta
Involved in menstrual cycle, pregnancy(supports gestation),prepares uterus for implantation
Used in Hormone receptor positive cancer.Used as Oral Contraceptives.
Normal menstrual bleeding is a Progesterone withdrawal
bleeding
To control ovulatory bleeding
S.A.R. of Progesterone.
1)Progesterone receptor favors a ∆4-3-one A ring in an inverted 1β,2α configuration.2)17-α hydroxyprogesterone is itself inactive but 17-α hydroxyprogesterone caproate is active.3)17-esters at C-6 of the B-ring yields orally active compounds.(medroxyprogesterone acetate, megestrol acetate).4) 19-Nor Compounds: ethynyl substituent at C-17 decreases hepatic metabolism and yields 19-nor testosterone analouges( norethindrone & norethynodrel) which are orally active.
HORMONE SOURCE PHYSIOLOGICAL ACTION
THERAPEUTIC ACTION /USE
S.A.R
Glucocorticoid Adrenal cortex
1)Stimulates gluconeogenesis
1)Potent anti-inflammatory and immunosuppressive activity.
1)4-5 double bond & 3 keto group of ring A are essential for activity.
Mineralocorticoid/ Aldosterone
2) Stimulates fat breakdown in
adipose tissues.
2) Short – medium acting: hydrocortisone, prednisone, prednisolone.
2)11-β hydroxy group is required for GC and not for MC activity
3)Inhibits glucose uptake in muscles &
adipose tissue.
Intermediate acting: triamcinolone,fluprednisolone
3) A hydroxy group at C-21 is essential for MC & not for GC activity.
4)Maintains normal concentration of
glucose.
Long acting:Betamethasone, dexamethasone.
3) As Bronchodialator
4) Used in shock.
QUIZ ON STEROIDS1.Which of the following is not a parenteral androgen?
(A) testosterone (B) testosterone propionate (C) testosterone ethantate (D) methyl testosterone.
Answer:- (D) methyl testosterone. (oral)
2.Example of an aromatic ring containing steroid– estradiol
3)Drugs used in doping and banned by IOC- androstanedione, nandrolol, stanozol, methyl testosterone.
4)Which of the following is not a naturally occurring female hormone?
(a) oestradiol (b) oestriol (c) mestranol (d) oestrone
Ans:- (c) mestranol.
5) Oestrogen is synthesized from- Androstendione.
6) Structural feature important for both glucocorticoids and mineralo corticoids:- 3-keto group on Ring A.
7)The inactive derivative of progesterone is :- 17α-hydroxy progesterone.
8) The steroid metabolite that acts as main regulator of gonadotropin secretion is:- Androstendiol.
9) An orally active progestrine:- norethindrone.
10) The reagent for conversion of hydrocoetisone to cortisone acetate is:- Cr2O3
11)Example of aromatic ring containing steroid:- estradiol, estriol
12) 19 carbon atoms containing sex steroidal hormone:- Androgen