9/9/2020

CHEM 445 (ELECTIVE COURSE)

CHEMISTRY OF NATURAL PRODUCTS
FOR CHEMISTRY’ STUDENTS, COLLEGE OF SCIENCE
PRE-REQUISITES COURSE; CHEM 341
CREDIT HOURS; 3 (2+1)

Prof. Mohamed El-Newehy

Chemistry Department, College of Science, King Saud University
http://fac.ksu.edu.sa/melnewehy/home

INTRODUCTION
o The chemistry of the Natural products include their biosynthesis, extraction,
identification, quantification, structural elucidation, physical and chemical properties
and reactions.
o Natural products are those chemical compounds or substances that are isolated
from living organism like plants, animals, fungi, and bacteria.

o They are produced by the pathway of primary or secondary metabolism

o Metabolism is defined as series of enzyme catalyzed biochemical reaction or

transformation occurring within the cells of an organism which are mainly required for
its growth, development and for proper response to its environment.
o The natural products are the end of organism metabolism called metabolites, which
perform different functions in animals and plant
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INTRODUCTION
o Metabolites: are the intermediate or products of metabolism, the term metabolites is
usually restricted to small molecules

 Primary metabolites
A primary metabolites is directly involved in normal Growth, development and
reproduction.
Example; carbohydrate, protein, fat and oil, alcohol e.t.c.
 Secondary metabolites
Secondary metabolites are not directly involved in growth, development and
reproduction of an organism (not important for the organism survival), but
they have an ecological function.

INTRODUCTION: DIFFERENT SOURCES OF NATURAL PRODUCTS

 Plants
• Plant is one of the major source of natural products.
• The natural products isolated from the plants depends on
‐ Plant species: different species produces different metabolites.
‐ Variability in growing conditions: different growing condition also result
different metabolites in the same species.
‐ Different part of the plants mostly contained different metabolites.

 Microbes
• Bacteria and microbes are the important source of natural products.
• The fermentation, followed by purification results some useful natural products.
These natural products are very useful as antibiotic.
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INTRODUCTION: DIFFERENT SOURCES OF NATURAL PRODUCTS

 Marine organism
• They are also important source of natural products.
• However, their collection is more challenging than plants.
• The chemistry of marine natural products will influenced by different variables
‐ Currents and sediments.
‐ pH levels.
‐ Atmospheric constituents.
‐ Metamorphic activity
‐ Ecology.
‐ Curacin A is obtained from a marine cyanobacterium and shows potent
antitumor activity.

INTRODUCTION: DIFFERENT SOURCES OF NATURAL PRODUCTS

 Animal
• Animals also yield natural chemicals which are important.
• Potent analgesic compound called epibatidine has obtained from the poisonous
skin extracts of the Ecuadorium frog.
• The snake venom and toxin also contained some useful peptides based natural
products.
• These peptides based natural products have specific interaction with
macromolecules and cells. Like bungarotoxin from cobra snake.

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INTRODUCTION: MAJOR CLASSES OF NATURAL PRODUCTS

• Peptides (basically consist of amino acids).
• Fats and oils
• Vitamins.
• Terpenes (Terpenoids).
• Steroids.
• Alkaloides.
• Phenolic compounds (Flavonoids)

o They does not include proteins, carbohydrates, and nucleic acids

o MW: ~150 ~ <800 amu (“small molecule”).

INTRODUCTION: WHY NATURAL PRODUCTS?

 Natural products are the source of the most complex and fascinating
chemical structures.
 Natural products represent biological diversity.
 Natural products are expressions of the genome.
 Natural products represent natural biological activity, whether as single
compounds or as complex mixtures.
 Natural products are part of the natural wealth of the country, and can be an
important source of livelihood, from agriculture and food, pharmaceuticals,
fine chemicals industry.
 Natural products can be an effective bridge from tradition to modern
scientific developments, including genetics, molecular biology,
biotechnology, and pharmaceutical science. 8

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NATURAL PRODUCTS: HISTORICAL PERSPECTIVE

o The use of natural products, especially plants, for healing is as ancient and
universal as medicine itself.
o The therapeutic use of plants certainly goes back to the Sumerian
civilization, and 400 years before the Common Era, it has been recorded
that Hippocrates used approximately 400 different plant species for
medicinal purposes.
o Natural products played a prominent role in ancient traditional medicine
systems, such as Chinese,
o According to the World Health Organization (WHO), 75% of people still rely
on plant‐based traditional medicines for primary health care globally.
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NATURAL PRODUCTS: PRESENT AND FUTURE

o An impressive number of modern drugs (~40% in use) have been derived
from natural sources, many based on their use in traditional medicine.
o Nature has been a source of therapeutic agents for thousands of years.
• Between 1983 and 1994; natural products or their derivatives, and 60–
80% of antibacterial and anticancer drugs were from natural origins.
• In 2000, approximately 60% of all drugs in clinical trials for the multiplicity
of cancers had natural origins.
• In 2001, eight (simvastatin, pravastatin, amoxycillin, clavulanic acid,
azithromycin, ceftriaxone, cyclosporin, and paclitaxel) of the 30 top‐selling
medicines were natural products or their derivatives, and these eight
drugs together totaled US $16 billion in sales. 10

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NATURAL PRODUCTS: PRESENT AND FUTURE

o Natural products are used directly in the ‘‘natural’’ pharmaceutical industry.
o The use of herbal drugs is once again becoming more popular in the form of
food supplements, nutraceuticals, and complementary and alternative
medicine.
o Natural products can contribute to the search for new drugs in three
different ways:
1. by acting as new drugs that can be used in an unmodified state (e.g., vincristine from
Catharanthus roseus).
2. by providing chemical ‘‘building blocks’’ used to synthesize more complex molecules
(e.g., diosgenin from Dioscorea floribunda for the synthesis of oral contraceptives).
3. by indicating new modes of pharmacological action that allow complete synthesis of
novel analogs (e.g., synthetic analogs of penicillin from Penicillium notatum).
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NATURAL PRODUCTS: IMPORTANT FIELDS OF APPLICATIONS

Healthcare
o The discovery of antibiotics,
 In 1943, Selman A. Waksman discovered streptomycin, an active
ingredient of the mould Streptomyces griseus;

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NATURAL PRODUCTS: IMPORTANT FIELDS OF APPLICATIONS

Healthcare
o The discovery of antibiotics,
 Penicillin; The Scottish bacteriologist Alexander Fleming had already
discovered this material in 1928; however, its preparation proved very
difficult.
 In Britain and the USA, it was possible for the first time at the end of the
Second World War to obtain penicillin on a larger scale.
 Production in Germany was begun in 1944 by Hoechst.

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NATURAL PRODUCTS: IMPORTANT FIELDS OF APPLICATIONS

Fragrances
 Henry IV (1553–1610), the first Bourbon on the French throne, is believed to have
written as follows to his mistress, Gabrielle d’Estrées.
 5α‐androst‐16‐en‐3‐one and androsta‐4,16‐dien‐3‐one act as attractants for women.
 pregna‐4,16‐diene‐3,20‐dione acts as attractants for men.

 α‐damascene is responsible for the scent of roses.

 α‐Damascone may be prepared on an industrial scale.
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NATURAL PRODUCTS: IMPORTANT FIELDS OF APPLICATIONS

Colorants
 Indigo, a natural dye extracted from the leaves of certain plants; nowadays synthetic
indigo is an essential colorant for our “leisure look”

 Salmon, the farmed fish are fed the naturally occurring carotenoid dyestuff
astaxanthin, in the form of amorphous nanoparticles, as part of their regular diet.

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NATURAL PRODUCTS: GENERAL ISOLATION STRATEGY OF NATURAL PRODUCTS

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NATURAL PRODUCTS: GENERAL ISOLATION STRATEGY OF NATURAL PRODUCTS

 Extract the dried and ground plant material with a suitable solvent.

 Concentrate the extract.

 Separate and purify each component.

 Since the concentrate contains an enormous variety of compounds, early isolations

involved selective crystallization of the most dominant component in the mixture.

 Liquid natural products were distilled.

 Natural organic acids were isolated by aqueous basic extraction and natural organic
bases (alkaloids) were isolated by aqueous acidic extraction.

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NATURAL PRODUCTS: CLASSICAL STRUCTURAL ELUCIDATION IS DONE BY

 Determination of functional groups.

 Determination of the carbon skeleton and the location of the functional groups.
 Degradation to smaller fragments (A‐B‐C ‐‐‐‐‐‐> A + B + C)
 Elemental analysis (CHN).
 Reactivity (leading to new reactions)
 Stereochemistry.
 Synthesis of the smaller fragments (A, B, C) and the entire molecule (A‐B‐C).
 Classification of the compound into a biogenetic family of compounds.
 More modern structural elucidation and characterization by spectroscopy including
NMR, MS, ESR, IR, X‐ray, UV
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NATURAL PRODUCT CHEMISTRY IN THE CHEMICAL INDUSTRY

 What special features characterize the production of natural compounds or their
derivatives on a technical scale?

 Property or activity of a natural product was often used in the past without isolating the
pure material – and of course mostly without any idea of its chemical structure.

 Often centuries, or at least decades, passed between the first use of the natural product
and the determination of its chemical structure.

 Once the structure was known, by means of targeted modifications it became possible
to develop analogues with new or improved properties: new synthetic methods and
reaction conditions could then be developed.
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NATURAL PRODUCT CHEMISTRY IN THE CHEMICAL INDUSTRY

 Nowadays, the development of new syntheses is a key aspect and an
important prerequisite for the industrial production of natural products.

 In 1975, James B. Hendrickson defined the “ ideal synthesis” as one which:

creates a complex molecule … in a sequence of only construction reactions
involving no intermediary refunctionalisations, and leading directly to the
target, not only its skeleton but also its correctly placed functionality.

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