Lecture-Notes-2017

Terpenoids
Terpenes
• Terpenes are lipids composed of repeating five-carbon units
called isoprene units.
• An isoprene unit has five carbons: four in a row, with a one-
carbon branch on a middle carbon.

• Terpenes can be cyclic or acyclic, and may contain

heteroatoms.

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Terpenes
• To find an isoprene unit, start at one end of the molecule near a
branch point. Then look for a four-carbon chain with a one-
carbon branch. This forms one isoprene unit.

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Terpenes
• Terpenes are classified by the number of isoprene units
they contain. A monoterpene contains 10 carbons and has
two isoprene units; a sesquiterpene contains 15 carbons
and has three isoprene units and so forth.

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Terpenes
Figure 29.8
Examples of some
common terpenes

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Terpenes
• Biosynthesis of terpenes is accomplished in two ways:
[1] The same reaction is used over and over again to prepare
progressively more complex compounds.
[2] Key intermediates along the way serve as the starting
materials for a wide variety of other compounds.
• All terpenes are synthesized from dimethylallyl
pyrophosphate and isopentenyl pyrophosphate. Both of
these five-carbon compounds are synthesized, in turn, in a
multistep process from three molecules of acetyl CoA.

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Terpenes
• Pyrophosphate, abbreviated OPP, is often used as a
leaving group in biological systems. It is a good leaving
group because it is a weak resonance-stabilized base.

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 Terpenes
• The overall strategy for terpene biosynthesis from
dimethylallyl pyrophosphate and isopentenyl
pyrophosphate is summarized below.
Figure 29.9
An outline of terpene
biosynthesis

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Terpenes
• The biological formation of geranyl pyrophosphate from the
two five-carbon pyrophosphates involves three steps: loss of
the leaving group, nucleophilic attack, and loss of a proton,
as shown below.

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Terpenes
• The biological conversion of geranyl pyrophosphate to
farnesyl pyrophosphate involves the same three steps:

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Terpenes
• Two molecules of farnesyl pyrophosphate react to form
squalene, from which all other triterpenes and steroids
are synthesized.

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Terpenes
• Aqueous hydrolysis of geranyl and farnesyl
pyrophosphates forms the monoterpene geraniol and
the sesquiterpene farnesol, respectively.

• All other terpenes are biologically derived from geranyl

and farnesyl pyrophosphates by a series of reactions.
Cyclic compounds are formed by intramolecular
reactions involving nucleophilic attack of  bonds on
intermediate carbocations. 11
Terpenes
The biosynthesis of -terpineol and limonene occurs as
follows:

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Steroids
• Steroids are a group of tetracyclic lipids, many of which have
biological activity.
• Steroids are composed of three six-membered rings and one
five-membered ring, that are joined together as drawn.
• Many steroids also have methyl groups located at the two-ring
junctions as shown. These are called angular methyl groups.
• The steroid rings are lettered A, B, C and D, and the 17 ring
carbons are numbered as shown. The two angular methyl
groups are numbered C18 and C19.

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Steroids
• Whenever two rings are fused together, the substituents
at the ring fusion can be arranged cis or trans.
• To more easily see why this is true, consider decalin,
which consists of two six-membered rings fused
together.
• trans-Decalin has the two hydrogen atoms at the ring
fusion on opposite sides, whereas cis-decalin has them
on the same side.

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Steroids
• Three-dimensional structures of these molecules show how
different these two possible arrangements actually are.
• The two rings of trans-decalin lie roughly in the same plane,
whereas the two rings of cis-decalin are almost
perpendicular to each other.
• The trans arrangement is lower in energy, and therefore more
stable.

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 Steroids
• In steroids, the most common arrangement by far is the all
trans. Because of this, all four rings in the steroid skeleton lie
in the same plane, and the ring system is fairly rigid.
• The two angular methyl groups are oriented perpendicular to
the plane of the molecule.
Figure 29.10
The three-dimensional
structure of the steroid nucleus

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Steroids
• Cholesterol has eight stereogenic carbons, so there are 28 =
256 possible stereoisomers. In nature, however, only the
following stereoisomer exists:

• Cholesterol is essential to life because it forms an important

component to cell membranes and is the starting material for
all other steroids.
• Humans do not have to ingest cholesterol because it is
synthesized in the liver and then transported to other
tissues. 17
• Cholesterol is synthesized in the body from squalene (C30).
 Steroids
Figure 29.11
The biosynthesis of cholesterol

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 Steroids
• Several drugs are now available to reduce the level of
cholesterol in the bloodstream.
• These compounds act by blocking the biosynthesis of
cholesterol in its early stages. Two examples are
atorvastatin (Lipitor) and simvastatin (Zocor).
Figure 29.12
Two cholesterol-lowering drugs

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Steroids

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Steroids
• Synthetic analogues of these steroids have found important
uses, such as in oral contraceptives.

• Synthetic androgen analogues, called anabolic steroids,

promote muscle growth. Although they are used by athletes,
their use is not permitted in competitive sports.

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Steroids
• A second group of steroid hormones includes the adrenal
cortical steroids. Examples are cortisone, cortisol and
aldosterone.
• All of these compounds are synthesized in the outer layer of
the adrenal gland.
• Cortisone and cortisol serve as anti-inflammatory agents and
they also regulate carbohydrate metabolism. Aldosterone
regulates blood pressure and volume by controlling the
concentration of Na+ and K+ in body fluids.

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