2.1. STEROIDS General structure: steroids are a group of structurally related compounds which are widely distributed in animals & plants. Steroids include variety of compounds such as bile acids, sex hormones, sapogenins, adrenal cortex hormones, steroidal alkaloids etc. & they have tetracyclic carbon skeleton, 1,2-cyclopentenoperhydrophenanthrene nucleus in their structure. Tetracyclic ring systems- 4 rings designated A,B,C,D (3 six member & 1 five member rings fused). A,B,C rings are in the chair confirmation but rigidity of fusion prevents ring flpping. A steroid can be defined as any compound which yields Diel’s hydrocarbon when distilled with selenium at 360 0 C. 13 14 9 8 10 17 12 11 15 16 7 5 6 CH 3 R 1 4 2 3 H H H R
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2.1. STEROIDSGeneral structure: steroids are a group of structurally related compounds which are widely distributed in animals & plants. Steroids include variety of compounds such as bile acids, sex hormones, sapogenins, adrenal cortex hormones, steroidal alkaloids etc. & they have tetracyclic carbon skeleton, 1,2-cyclopentenoperhydrophenanthrene nucleus in their structure. Tetracyclic ring systems- 4 rings designated A,B,C,D (3 six member & 1 five member rings fused). A,B,C rings are in the chair confirmation but rigidity of fusion prevents ring flpping. A steroid can be defined as any compound which yields Diel’s hydrocarbon when distilled with selenium at 3600C.
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CH3
R1
4
2
3
H
H
H
R
Classification:
Steroids R Rl
Sterol -CH3 CH3-CH-(CH2)3-CH(CH3)2
Bile acids -CH3 CH3-CH-(CH2)2-COOH
Saponins -CH3 8 carbon ketosproacetal
Sex hormones
i)Oestrogens - -OH or >CO
ii)Corpus luteum(Gestrogens)
-CH3 -COCH3
iii)Androgenic -CH3 -OH or >CO
iv)Adrenal cortical substance
CH3 -COCH2OH
Structure
1) Sterol e.g. Cholesterol 2) Bile acids e.g. Cholanic acid
3) Saponins e.g. Plant Sapogenin 4) Sex hormones i) Oestrogen e.g.estrone
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12
11
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20CH318
CH319
1
23
22
4
CH321
24
2
3H
H
H
H25
CH327
CH326
OH
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20CH318
CH319
1
22
4
CH321
2
3
H
H
H
H
H
O
OH
CH3
CH3
H
H
H
O
OCH3CH3
H
H
OH
CH3
H
H
H
O
OH
ii) Corpus Luteum Hormones e.g. Progesterone iii) Androgenice.g. Androsterone
iv) Adrenal Cortical Hormones e.g. Cortisol
CH3
CH3
H
H
H
CH3
H
O
OCH3
CH3
H
H
H
O
OH
CH3
CH3
H
H
H
OH
O
OOH
OH
Corticosteroids:
• Occurrence: corticosteroids are the characteristic adrenal cortical hormones. Cortex (the outer region of adrenal gland) which produces the adrenocotical hormones or corticoids. The production of corticoids is controlled by a hormone produced in the anterior lobe of the pituitary body, is called adrenocorticotropic hormone(ACTH).
Cortisone
CH3
CH3
H
H
H
OH
O
O
O
OH
Biological role: 1) To help in carbohydrate, lipids and protein metabolism. Decreases in carbohydrate metabolism leads to Edison’s diseases. Deficiency of these hormones leads to disturbance of these metabolism & finally to death. The deficiency also leads to muscular weakness or decrease in resistance to shocks.
2) To help the electrolyte HCl, K, Cl metabolism. Maintain proper electrolyte balance in the body fluids. These deficiency leads to disturbances in this metabolism & finally to death.
3) Cortisone is used in rheumatoid arthritis. This is given with antibiotics to increase the effect of antibiotic.
4) Hydrocortisone is used in ear & nose drops.
Structural features: For all the naturally occurring adrenal cortical hormones two structural features are essential for their biological actions: a) presence of an α,β- unsaturated ketonic group (a double bond between C4 & C5 and a ketonic group at C3) & b) presence of a ketonic group at C20. However, the other functional groups on other positions also exhibit some specific & important functions e.g. i) hydroxyl group at C21 increases sodium retention & is necessary for carbohydrate metabolism.
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Steroidal hormones
Occurrence: Steroidal hormones are divided into two main types: sex hormones & adrenal cortical hormones. Sex hormones are produced in the gonads (ovaries in female & testes in male) under the stimulation of proteinous hormones secreted in the anterior lobe of the pituitary gland & carried to the gonads through the stream of blood. Sex hormones are divided into three types : oestrogens which consist of oestradiol,oestrogen,oestriol,etc.,gestogens are progesterone & androgens which consist of testosterone & androsterone. The ovary produces mainly oestradiol & progesterone, the testes secrete testosterone. The main sources for the oestrone are urine of non-pregnant or pregnancy women, pregnant mares, human placenta & the adrenal cortex. The main source of the progesterone is corpus luteum,placenta,pregnancy urine & adrenal cortex. Androsterone is occurred in urine of male & female animals & the testicular extract.
Biological role of sex hormones: 1) the sex hormones are responsible for the sexual processes & for the secondary characteristics by which a male can be differentiated from a female e.g. texture of skin, distribution of hair on the body, voice etc. 2) the sex hormones also take part in the various anabolic & catabolic reactions taking place in the body. 3) they participate in the regulation of calcium & phosphorous levels in the blood. 4) during the menopause, some women are put into negative calcium & phosphorous balance which leads to a painful condition. The administration of sex hormones helps in maintaining the normal calcium & phosphorous level.
ii) Presrnce of either –OH or .CO at C11 is necessary for carbohydrate activity & decreases sodium retention.Iii) hydroxyl group at C11 increases carbohydrate activity.On the basis of the above (ii) point the seven active hormones can be divided into three main types:a) which are oxygenated at C11. They help in carbohydrate & protein metabolism.b) which are not oxygenated at C11 e.g. 11-deoxy &11-deoxy-17-hydroxycorticosterone. These hormones are not active in carbohydrate & protein metabolism.C) which is oxygenated at C11 & its methyl group at C18 is replaced by an aldehyde group e.g. aldosterone. This hormone affects both mineral (Na,K,Cl etc.) & organic metabolism.Cortisol is physiologically more active than cortisone.They are secreted in response to ACTH. The structure of cortisol is same as cortisone with the only difference that there is an –OH group at C11 instead of .CO group.
Biological role of oestrones: The main physiological function of oestrone is to induce the state of heat in the female animals, thus acts in the control of uterine cycle. It also stimulates the development of female secondary sex characteristics by which they are differentiated from males.
Structure:
Stereochemistry of oestriol Since oestriol does not form isopropylidene derivative with acetone that is its two adjacent hydroxyl groups must be trans the configuration of hydroxyl group at C17 is found to be β.
CH3
H
H
H
OH
OH CH3
H
H
H
OH
OH
CH3
H
H
H
OH
OH
OH
Oestradiol: There are two stereoisomeric oestradiols α & β.
Oestradiol-17β is much more reactive than Oestradiol-17α. The β-isomer was isolated from the ovaries of sows. The α-isomer was isolated from the pregnancy urine of mares.
Oestradiol-17β Oestradiol-17α
Testosterone is the male hormone secreted by testes & metabolized to androsterone & dehydroepiandrosterone which are excreted through urine. They are less active than testosterone. Their activity & secretion is controlled by interstitial cell stimulating hormones.
CH3
H
H
H
OH
OH CH3
H
H
H
OH
OH
Structure of androsterone: 5α-cholestanyl-3β-acetate on oxidation with CrO3 in acetic acid forms epiandrosterone but not androsterone. But 5α-cholestanyl-3α-acetate on oxidation forms androsterone. This reaction indicates that configuration of –OH at C-3 is α.
5α-androsterone 5β-androsterone
Testosterone Dehydroepiandrosterone
CH3
CH3
H
H
H
OH
O
H
CH3
CH3
H
H
H
OH
O
H
CH3
CH3
H
H
H
O
OH CH3
CH3
H
H
H
OH
O
On comparing the molecular formul of androsterone & dehydroepiandrosterone, it is found that latter has two H-atoms less than the former. Thus, it is simply androsterone with one double bond.
Steroidal alkaloids: Occurrence: They are glycosides which are found in plants belonging to the family solanaceae. The two members are solanine-t from potato(solanum tuberosum) & solanin-s.structure: On hydrolysis they give sugar molecules & the aglycone solanidine-t & solanidine-s. They are divided into two groups: 1) one group of compounds in which nitrogen is in the steroid nuclear skeleton. 2) The other group in which nitrogen is in one or more side chains. They may be classified structurally into five groups based on the parent carbon skeleton.i) Pregnane alkaloids e.g. furtumine,coressine.Ii) solanum alkaloids: The solanum alkaloids are C-27 steroids having a basic character & can be divided into two classes: steroids with a secondary nitrogen,e.g. solasodine & steroids with a tertiary nitrogen in fused ring system e.g. solanidine-t
solasodine solanidine-t
CH3
CH3
H
H
H
N
CH3
H
H
CH3
OH
CH3
CH3
H
H
H
O
NHCH3CH3
H
OH
Holarrhimine Biological: Solanum alkaloids are surface active, haemolytic form molecular compounds with cholesterol & toxic when ingested. The bark of kurchi shrub(holarrhena antidysentrica) used as a remedy for amoebic dysentry. Veratrum alaloids increase the work performance of the failing heart.
iii) veratrum alkaloids occur in the roots & rhizomes. They are not strictly steroids as they contain a five membered C ring & a six membered D ring. e.g. veratramine.Iv) solamandra alkaloids e.g. solamandarine.v) kurchi alkaloids e.g. holarrhimine.
H
H
H
H
NH2
OH
CH3
NH2
Sterols: Occurrence: Sterols are found in animal & plant oils & fats. These are crystalline compounds containing a secondary alcoholic group. So they differ from common alcohols in being solid & due to this reason they are known as sterols.Classification: Sterols are divided into three groups, i) zoosterols: They are obtained from animals e.g. Cholesterol. ii) Phytosterols: They are obtained from plants e.g. stigmasterol. Iii) Mycosterols: They are obtained from yeast & fungi e.g. ergosterol.The main sources of cholesterol are brain, spinal cord, gallstone & fish liver oil.STEREOCHEMISTRY: As the structural formula of the saturated sterol shows that it has nine dissimilar asymmetric carbon atoms (eight in the nucleus & one in side chain viz. 3,5,8,9,10,13,14,17 & 20) so there are 29 =512 optical isomers .
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CH319
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CH321
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H
H
H
H25
CH327
CH326
The fusion of the ring A /B, B / C & C / D my be either in cis- or trans- manner. The rings A & B in steroids can be either cic or trans fused. In either, the variation in sterochemistry at C-5 rather than at other centres is more important. Saturated steroids like cholesterol are A / B trans- or 5α compounds (i.e. indicate allo) , the bile acids are A / B cis- or 5β compounds.The B / C ring is always fused trans manner, except those of heart poison.In sterols, bile acids & related compounds, the C / D ring is trans fused. But in cardiac giycosides, the C / D ring is cis fused. The fusion of the four rings confers rigidity to the steroid structure. Rings A, B, & C are cyciohexane rings(preferably a chair conformation) & the ring D is a cyclopentane ring.BILE ACIDS: : Occurrence:The liver secretes a clear, golden yellow viscous fluid known as bile. It is stored in the gall bladder & is mainly useful for digestive system. Bile consists of inorganic (HCO-
3, Cl-, Na+,K+etc.)ions as well as organic compounds. The bile acids are present as the sodium salt of amides with either glycine or taurine. E.g. sodium glycocholate & taurocholate. Bile acids are the hydroxy derivatives of either cholanic acid (5β – cholanic acid) & allocholanic acid (5α – cholanic acid ) & dehydration followed by reduction of the bile acids gives the cholanic or allocholanic acid.
Cholanic acid Allocholanic acid
Structures of 5β – cholanic acid (cholanic acid) & 5α – cholanic acid (allocholanic acid) have been established by means of synthesis from cholesterol.There are 20 natural bile acids in which the – OH takes any of the following positions 3,6,7,11,12 & 23 with α - configuration.1) deoxycholic acid = 3 α ,12 α –dihydroxy cholanic acid2) cholic acid = 3 α ,7 α ,12 α – trihydroxy cholanic acid3) lithocholic acid = 3 α – hydroxy cholanic acid.Biological functions of bile acids: 1)They facilitate digestion of fats by emulsifying them & thereby increasing the surface area of the material for pancreatic enzymes. Moreover, emulsifying process converts fats into water soluble compounds which can be easily absorbed in the intestine.
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CH321
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OH
H
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OH
H
2) They also activate the enzyme cholesterol esterase & pancreatic lipase.3) They help in the absorption of cholesterol fat soluble vitamins (A,D,K) etc by forming water soluble complexes.4) They also keep cholesterol in solution, if the ratio between bile acids & cholesterol falls than the normal, cholesterol is precipitated & forms gallstones in liver & gall bladder.
