Professional Documents
Culture Documents
Tim dosen :
Dr. Yustina Sri Hartini, Apt.
Dr. Erna Tri Wulandari, Apt.
Dandang gendiis (Clinacanthus nutans)
kencing manis/diabetes
Paracelsus (493-1541)
Schmidt & Seydler (1811/1815
Analecta Pharmacognostica
the oldest modern science?
At the end of the 18th century, crude drugs were still being used
as powders, simple extracts, or tinctures
Obat jadi
Obat
tradisional
Fig. 1. Explanatory model for molecular pharmacognosy
2 4
2 4
H
HO
3 1 N
H
4
N
HO
12 10
O H
13 9
N H CH3O
H H
5
15 N 10
6
7 16 CH3 O O
H N
HO
Morphine Strychnine
Quinine
(aromatic alkaloid from opium, (aromatic alkaloid from (quinoline alkaloid from
Papaver somniferum) Strychnos nux-vomica)
Cinchona species)
Isolation: 1806, Sertrner Isolation: 1818, Pelletier &
Isolation: 1820, Pelletier &
Structure: 1925, Robinson Caventou
Caventou
Synthesis: 1954, Ginsberg Structure: 1946, Robinson
Synthesis: 1944, Woodward
Biogenesis: 1959, Leete Synthesis: 1954, Woodward
2001, Eichberg
Some milestones in natural products chemistry:
10
CH3
CH3 N
1 O CO2CH3
2 N
O
9 8
C6 H5
7 H
CH3 CH3 O
4
Coniine
Cocaine
Camphor (aliphatic alkaloid from
(aliphatic alkaloid from
(monoterpene from hemlock, Conium
Erythroxylon coca)
Cinamomum camphora) maculatum)
Isolation: 1859, Niemann
Isolation: 1845, Bouchardat Isolation: 1886, Ladenburg
Synthesis: 1923: Willsttter
Structure: 1926, Koller
Some milestones in natural products chemistry:
21
24
20 23 26
18
CH3 25 OH N(H)CH3
27
CH2OH 19
CH3
11 13 17 CH CH CH3
14
O glucoside 1 9
10 8
3 5
6
HO
Ephedrin
Cholesterol (aromatic alkaloid from
Salicin (steroid from gallstones) Ephedra equisetrina and
(aromatic alcohol from
Isolation: 1909, Windaus E. sinica; "ma huang")
Salix species)
Structure: 1932, Wieland Structure and synthesis:
Structure and synthesis: Synthesis: 1964, Johnson 1920, Spth and Gring
1906, Irvine Biogenesis: 1966, Cornforth
Some milestones in natural products chemistry:
arabinose OH
glucose
OH
Ginsengoside Rs2 OH HO
HO OH O
(Panax ginseng) O
O
O
Isolation and structure: OH
1962, Shibata
glucose
HO
O
HO
O
Brevetoxin-A
HO
AcO O
(red tide toxin from
O
HO Gymnodinium breve)
HO
OH Structure: 1986, Clardy
glucose-6-acetyl Synthesis: 1987, Nakanishi
OH
O O
. CHO
. . . . .
O O
. .
O
O
O O
O
. O
O
Some milestones in natural products chemistry:
.
AcO O OH . .
H3C CH3 CO2H
O Ph O HO O HN .
O
CH3
Ph NH O OCH3
CH3 H
OH H O
HO AcO
PhCO2 HO O OH
Taxol
(antitumor diterpene from Dynemicin A
Pacific yew, Taxus species) (antibiotic polyketide from
Micromonospora chersina)
Isolation: 1971, Wani et al.
Structure: 1971, Wani et al. Structure: 1989, Matsumoto and Clardy
Synthesis: 1991, Nicolau
Biosynthesis: 1992, Tokiwa et al.
Some milestones in natural products chemistry:
OH
OH
O
O H
H OH
H
O
O O
O
OH
O H O
O OH
O
OH
(+)-Absinthin O
(dimeric diterpene from Artemisia (-)-Littoralisone
absinthium L., an anthelmintic)
(neurotrophic growth factor, iridoid
Isolation: 1953, Herout from Verbena littoralis L.)
Structure: NMR: 1980, Beauharie,
Isolation and structure: 2001, Li
X-ray: 1985, Karimov
Synthesis: 2005, Mangion
Synthesis: 2004, Zhang
Artemisia annua
Artemisinin
P. falciparum vs cincin peroksida
Triptolide
antiproliferatif ca pankreas vs
diterpenoid epoksid
Tripterygium wilfordii Celastrol
antioksidan, anti-
inflammatory,[anticancer, and
Celastrus regeliii insecticidal activities. obesity-
controlling effects in mice vs
pentasiklik triterpenoid
Zingiberacea
Capsaicin
Capsicum sp sensasi panas, iritan utk mamalia
Curcumin
Belajar di praktikum FF
Natural Products as Sources of New Drugs
(Ref: Newman, Cragg, and Snader, Natural Products as Sources of New Drugs over the Period 1981-2002,
J. Nat. Prod. 2003, 66, 1022-1037)
they can be
1. Entire organism (plant, animal, organism)
2. Part of an organism (a leaf or flower of a plant, an
isolated gland or other organ of an animal)
3. An extract or an exudate of an organism
4. Isolated pure compounds
Why do we need plants?
1. Source of drug molecules
Most drugs can be synthesised
Still more economical to use the plant
Papaver opium -> morphine, codeine (strong medicinal
pain)
Quinine
Dihydromorphinone:
Reduced =, oxidised 2y alc. Potential analgesic.
5. Source of novel structures
these might never be thought of
Tapak dara /Catharanthus periwinkle (Vinca
rosea) -> vincristine (alkaloid dimer)
6. Source of plant drugs
As a powder or extract
The pure compound is often not isolated because:
Active ingredient is unknown
Active ingredient is unstable
Isolation process is too costly
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Issues and challenges in Natural Products today
1. Loss of biodiversity
2. Intellectual Property Rights
Patent protection (pharma companies)
Biopiracy (source countries)
3. Western drugs:
a. High cost of drug development
b. New drug leads and targets
4. Herbal products:
a. Regulation
b. Improvement in quality
c. Elucidation of mechanism of action
39
Research areas in natural products today
1. Structural elucidation (speed of analysis, sample throughput complexity
of structures)
2. Metabolonomics
3. Synergy and biotransformation
4. Biosynthesis
5. Biological activity
a. Ecological
b. Pharmaceutical properties / drug discovery
c. Healthcare and cosmetic products
6. Molecular biology and Biotechnology
7. Quantitative natural products chemistry
40
The study of natural products is multidisciplinary
Biology Chemistry
Genomics . Proteomics
Metabolonomics
Techniques used in natural products chemistry
1800 1850 1900 1950 1975 2000
Techniques used:
basic physico-chemical measurements
TLC column chrom GC HPLC / Electrophoresis
X-ray UV-vis IR MS / NMR
Radioisotopes
Enzymes Computational methods
Tissue culture
Mol Bio / Biotech
Combinatorial chem
Modern directions in natural products chemistry:
Genomics of bacteria and plants
Novel and efficient synthetic methods
Genetic engineering of bacteria and plants
Enzyme synthesis
Computational methods and modeling
High efficiency chromatography
Spectroscopic methods
High-throughput screening
Synergism
Biotransformation
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