What is “Natural Product”?

Natural Products and Drugs

Yan Zhang, Ph.D.
Department of Medicinal Chemistry
Room 534, Smith Building
Email: yzhang2@vcu.edu
Tel: 8280021
• Pharmacognosy
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Where are they from?

Why natural product?
• More than 30% of the current worldwide human
therapeutics sales are plant or microbial origin.
• Compounds from nature often open up completely
new therapeutic approaches.
• Natural products substantially contribute to
identifying and understanding novel biochemical
pathways in vitro and in vivo.
• Natural products often provide novel chemical
structural skeletons.

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Morphine Quinine
N CH3

HO
N

O
O H3C
HO OH
N

• One of the most commonly

Analgesic cited rainforest medicinal plants
is the Cinchona tree. This
Abuse and addiction plant's bark is the source of
CNS-mediated respiration quinine, a highly effective drug
depression, etc for treatment of malaria.

E. Merck, 1826
• 1820 first isolated as pure
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principle 6

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 Aspirin (Bayer, 1899) Taxol (BMS, 1993)
OH
O HO
HO
HO O O
OH
OH
OH Salicylic acid
Salicin

H3C O

O
Acetylsalicylic acid
O

OH

• analgesic, antipyretic
antirheumatic, etc.
Yew tree (Taxus brevifolia)
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Semisynthesis of Taxol Huperzin A

CH3

NH
O
H3C
H2N

Acetylcholinesterase inhibitor

Alzheimer’s disease

08/2005, Phase II, NIH/NIA

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Where are they from?

Artemisinin (Qinghaosu)
Me
H
Me O
O
H
HO
Me
O

Artemisinin (Qinghaosu)
Me
H
Me O
O
H
HO
Me
H OMe
Treatment of certain types of Malaria
Artemether 11 12

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 Penicillin Acarbose and Miglitol
HOH2C OH
HO
H3C H
N
HO O HO
HO N H OH
H H OH
HO HO
H O
HO OH
HO H OH
H OH HO OH
H O
HO
Acarbose H OH OH
H
Miglitol

Inhibitor of α-glucosidase too

• From culture broth of Penicillium From culture broth of Actinoplanes sp.
H H
N S notatum Bayer, 1996
CH3 Inhibitor of α-glucosidase
• An efficient antibacterial
O N CH3
O therapeutic without substantial Starting material is
COOH side effects Bayer, 1990 1-deoxynojirimycin, from
• Merck, 1941 Streptomyces culture broths or
13 bark of mulberry trees 14

Neucarzinostatin and Dynemicin A Where are they from?

CH3
CH3
COOH
O OH O HN
H3CO OH O
O OMe
O O O
O
OH O OH
O
NHCH3 Dynemicin A
O

H3C OH
OH From actinomycetes
Neocarzinostatin

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Maitotoxin Brevetoxin B

Ptychodiscus brevis
Gambierdiscus toxicus
May interact with
binding site-5 of sodium
Channels and leading to a
3,422 Dalton, water-soluble polyether-type neurotoxin
Continuing influx of sododium
Calcium transportation (influx)
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3
 Palytoxin
Tetrodotoxin and Bryostatin 1
O

O
O OH NH2

N
HO H
N
HO H Palythoa toxica
OH

Tetrodotoxin • 2,680 Dalton

• To stimulate arachidonic acid
Bryostatin 1 metabolism synergistically with
To affect protein kinase C at pM TPA-type promoters
Anticancer treatment?

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Where are they from? Some steroids

Me OH Me O Me OH

Me Me Me

O O O
OH
Testosterone Androstenedione 5α-dihydrotestosterone (DHT)

Anabolic and androgenic activity

Me OH Me O Me OH

OH

HO HO HO

Estradiol Estrone Estriol

Female sex hormones

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Classifications Secondary Metabolism

• By sources:
– Plant
– Animal
– Microorganism
– Marine environment
• By activity
• By structural character

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