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Biosynthesis & Pharmacognosy

CS407

Paraic James

18h

Peter Kenny

18h

Introduction
Main Biosynthetic Pathways
Biosynthesis of Carbohydrates (Glucose)
Pyruvate & Acetate Formation
Fatty Acids
Prostaglandins
Shikimate
Amino Acids

Alkaloids
Morphine Biosynthesis
Nucleotides
Pyrrole Pigments
Aromatic Polyketides
Terpenes
Steroids
Mixed Pathways
Plant Sources of Drugs
Flavanoids
Spectroscopic Techniques

Books:
Basic Organic Chemistry Part IV
Tedder, Nechvatal, Murray, Carnduff

Organic Chemistry
I.L.Finar

Natural Products
J.Mann, R.S.Davidson et. al.

Medicinal Natural Products


P.Dewick

Organic Chemistry of Biological Pathways


McMurry, Begley

Biosynthesis
- Synthesis by Nature

Primary Metabolites

&

Secondary Metabolites

Proteins

Terpenes

Carbohydrates

Steroids

Fatty Acids

Alkaloids

Nucleic Acids (DNA etc.)

Pharmacognosy
Pharmakon

Greek for

DRUG

gnosis

Greek for

KNOWLEDGE

-Study of Drugs of NATURAL ORIGIN

MAIN BIOSYNTHETIC PATHWAYS


All start with CO2 + H2O and their conversion to
Carbohydrates during PHOTOSYNTHESIS

CO2 + H2O

C6H12O6 + O2
Glucose

C6H12O6
Glucose

O
H3C

COOH

Pyruvic Acid (C3)


Pyruvate CH3C(O)COO-

H3C

OH

Acetic Acid (C2)


Acetate CH3COO-

3 PRINCIPAL STARTING MATERIALS


FOR BIOSYNTHESIS OF
SECONDARY METABOLITES

1. ACETATE
2. SHIKIMATE
3. AMINO ACIDS

Acetate (C2) is a major Building Block for:


FATTY ACIDS
POLYKETIDES
PROSTAGLANDINS

Acetate is also used to make Mevalonic Acid (C6)


O
H3C

H3C
HOOC

OH

OH
OH

Mevalonic Acid

Mevalonate is is used a building block for:


TERPENES
STEROIDS (e.g. Cholesterol)

Pyruvate (C3) combines with Carbohydrate


to produce:
Shikimic Acid (C7)

COOH

HO

OH
OH

Shikimate is the precursor for:


AROMATIC AMINO ACIDS
CINNAMIC ACID DERIVATIVES
LIGNANS

There a number of routes to formation of Amino


Acids.
Amino Acids are important precursors for:
ALKALOIDS
PURINES
PROTEINS
PYRROLE PIGMENTS

Establishment of Biosynthetic Pathways:

1. Use ISOTOPIC TRACERS:

13

14

18

32

Follow the label from starting material to


product

H3C
O

O
H3C

COOH
O

14

C labelled Acetate

CH3
COOH
OH
6-Methylsalicylic Acid

Labelled Acetate provides all the Carbon in


6-Methylsalicyclic Acid
(Label finishes up on every second Carbon in
a predictable manner)

Knowing where the label was in the starting


material we can predict where it will be in the
product.

Problems:
Difficult to synthesize labelled precursors
Difficult to get good incorporation of the
label into living organisms
Difficulties arise with dilution of the label
by the unlabelled pool
Usually only a small amount of product and
difficult to establish exact location of the
label

Also difficult to establish the exact sequence


unless the products can be isolated at different
time intervals

Label will appear in B before appearing in C

2. Use Abnormal MUTANT systems


Block one step of the sequence e.g. missing
enzyme will cause build-up of the starting
material (B) for that step and later compounds
will not be formed (C).