Steroids

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Definition Numbering and ring letters

Steroids are compounds

possessing the skeleton of
cyclopenta[a]phenanthrene
or a skeleton derived
therefrom by one or more
bond scissions or ring
expansions or
contractions”…IUPAC
 Definition of steroids and sterols
• Methyl groups are normally present at C-10 and C-13.

• An alkyl side chain may also be present at C-17.

• Sterols are steroids carrying a hydroxyl group at C-3

and most of the skeleton of cholestane.

• Additional carbon atoms may be present in the side

chain.
 Absolute configuration
• The absolute configuration is defined by:
– The parent name for some chiral centres.
8,9,10,13,14
– α, β, R or S for other Centres
– χ for unknown.

• Are preceded by the respective locants e.g. 5α

 Orientation of Projection Formulae

• An atom is termed:
– α if it lies below the plane of paper
– β if it lies above the plane of paper

• Bonds to atoms or groups:

– α depicted as broken lines ( / )
– β depicted by solid lines preferably thickened
– χ denoted by wavy lines
Note*

*IUPAC Recommendations 1989

 Note.
• Hydrogen atoms at the bridgehead C-8, C-9 and
C-14 may be omitted if there is no ambiguity.

• If one of the hydrogen atoms is replaced, e.g. by a

fluorine atom, care must be taken in the correct
use of broken and bold lines.

• The bond to a bridgehead hydrogen atom should

never be drawn without the H. (Methyl Group!!)
Stereochemistry of ring junctions and side-
chain attachment

Unless implied or stated to the contrary, use of a

steroid name implies that atoms or groups
attached at the bridgehead positions 8, 9, 10, 13
and 14 are oriented as shown in formula (prev.
Slide) (i.e. 8β,9α,10β,13β,14α),
 Stereochemistry of ring junctions and
side-chain attachment…case of C5

The configuration of hydrogen (or a substituent)

at the bridgehead position 5 is always to be
designated by adding α or β after the numeral 5,
this numeral and letter being placed immediately
before the stem name.
 Fundamental Carbocycles, Unsaturation
Gonane
The parent tetracyclic hydrocarbon without methyl groups at C-
10 and C-13 and without a side chain at C-17 is named gonane.
Fundamental Carbocycles, Unsaturation
Oestrane/Estrane
The hydrocarbon with a methyl group at C-13 but
without a methyl group at C-10 and without a side chain
at C-17 is named Oestrane/Estrane.
Fundamental Carbocycles, Unsaturation
Androstane
• The hydrocarbon with methyl groups at C-10 and C-
13 but without a side chain at C-17 is named
androstane.
Common and Systematic Nomenclature :
Ergosterol and Stigmasterol
Nomenclature and Numbering
Nomenclature and Double Bonds
• Classification of Steroids

• Sterols

• Sex Hormones
– Classification

• Androgens
– Androsterone
 Overview
• The steroids include a broad-spectrum of important
compounds:

– adrenal cortical hormones,

– sex hormones,
– cardiac glycosides,
– antirachitic vitamins (Vitamin D),
– toad poisons,
– saponins,
– bile acids
– and some alkaloids.
 Overview
• They are important agents applied in:

– control and management of birth control,

– inflammatory conditions,

– hormone-replacement therapy (HRT),

– and above all in the treatment of neoplastic diseases (cancer).

 Classification of Steroids
Based on Substituent at C17

1. Sterols
– R is aliphatic
– One or more OH attached to alicyclic linkage

2. Sex Hormones
– R bears ketonic or alcoholic group
– Possess a 2 carbon side chain

3. Cardiac Glycosides
– R is a lactone ring
– “Glycoside” in nature

4. Bile Acids
– 5 Carbon side chain end with a – COOH Moiety.

5. Sapogenins
– R contains an oxacyclic (ethereal) ring system
 Cholesterol

(3β)-cholest-5-en-3-ol
 Cholestanol

IUPAC NAMe
(3Β)-CHOLEST-5-
EN-3-OL
• Cholesterol, is derived from the
• Ancient Greek word Chole - bile
• and stereos - solid
• Followed by the chemical
• suffix - ol for an alcohol, is an
• organic molecule.
• It is a derived lipid molecule –
• a sterol or modified steroid
• BODY CHOLESTEROL CONTENT
• For a man of about 68 kg (150 lb), typical
• total body-cholesterol synthesis is
• approximately 1 g (1,000 mg) per day,
•  Total body content of Cholesterol is
• approximately 35 g, primarily located
• within the membranes of all the cells of
• the body.
•  Typical daily dietary intake of additional
• cholesterol, is 200–300 mg
• INGESTED CHOLESTEROL
• Most ingested cholesterol is esterified, and
• esterified cholesterol is poorly absorbed
• . The body also compensates for any
• absorption of additional cholesterol by
• reducing cholesterol synthesis.
•  For these reasons, seven to ten hours after
• ingestion of cholesterol, blood levels will
• show little if any effect on total body
• cholesterol content or concentrations of
• cholesterol in the blood
• PRODUCTION OF CHOLESTEROL IN
• VERTEBRATES
• In vertebrates the hepatic cells
• typically produce greater
• amounts of Cholesterol than
• other cells.
• It is almost completely absent
• among prokaryotes (bacteria and
• archaea), although there are
• some exceptions such as
• Mycoplasma, which require
• cholesterol for growth.
• However, during the first seven hours
• after ingestion of cholesterol, the levels
• significantly increase
• Cholesterol is recycled.
• The liver excretes it in a non-esterified
• form (via bile) into the digestive tract
• .
• Typically about 50% of the excreted
• cholesterol is reabsorbed by the small
• bowel back into the bloodstream
 FUNCTIONS OF
Cholesterol
• CHOLESTEROL IS REQUIRED
• TO BUILD AND MAINTAIN
• MEMBRANES
• It modulates membrane
• fluidity over the range of
• physiological temperatures
• Cholesterol serves as a precursor
• for the biosynthesis of steroids
• hormones, bile acids, and vitamin D
• Cholesterol is the principal sterol
• synthesized by animals. All kinds of
• cells in animals can produce it.
• Recent studies show that vitamin D
• is a potent antioxidant, helping to
• detox the body and protect arteries
• too.
 CELL MEMBRAIN INTEGRITY

• It is biosynthesized by all

• animal cells because it is an
• essential structural component
• of animal cell membranes
•  It is required to maintain both
• the structural integrity and
• fluidity of the cell membrane
• (a) To protect membrane
• integrity/cell-viability cholesterol
• enables animal cells not to need a cell wall like
plants & bacteria
•  And thus animal cells are able to
• (b) change shape and
• (c) move about (unlike bacteria and
• plant cells which are restricted by
• their cell walls).
• The hydroxyl group on
cholesterol interacts with the
polar head groups of the
membrane
• phospholipids and sphingolipids
While the bulky steroid and the
• hydrocarbon chain are embedded
in the
• membrane, alongside the
nonpolar fatty acid chain of the
other lipids.
• Through the interaction with
the phospholipid fatty-acid
chains, cholesterol
• increases membrane packing,
which
• reduces membrane fluidity.
• The structure of the tetracyclic ring of
cholesterol contributes to the decreased fluidity
of the cell membrane as the molecule is in a
trans conformation making all but the side chain
of cholesterol rigid and planar.
• o In this structural role, cholesterol reduces the
permeability of the plasma membrane to neutral
solutes, hydrogen ions, and sodium ions.
• Within the cell membrane, cholesterol also
functions in intracellular transport, cell
signalling and nerve conduction.
Cholesterol is essential for the structure and
function of invaginated caveolae and clathrincoated
pits, including caveolae-dependent
and clathrin-dependent endocytosis
The role of cholesterol in such endocytosis
can be investigated by using methyl beta
cyclodextrin (MβCD) to remove cholesterol
from the plasma membrane
• PRECURSOR OF STEROID HORMONES
 Lipoprotein Classification
• 5 broad categories on the basis of their functional & physical
• properties, primarily on their DENSITIES:
• 1) Chylomicrons: Transport dietary TAGs and
• cholesterol from the intestines to the liver
• 2) VLDL — very low density lipoprotein;
• 3) IDL — intermediate density lipoprotein;
• 4) LDL — low density lipoprotein:
• A group of related particles that transport
• endogenous TAGs and cholesterol from
• the liver to the tissues.
• 5) HDL — high density lipoprotein: Transport
• endogenous cholesterol from the tissues
• to the liver.