terpenes and poliketydes
DESCRIPTION
kimia organikTRANSCRIPT
NATURAL PRODUCTSNATURAL PRODUCTS
PRIMARY AND SECONDARYPRIMARY AND SECONDARY METABOLISMMETABOLISM
ENERGY
h
CO2
O2
H2O
“N”
N2
NO2-/NO3
-/NH4+
TRACE METALS
Na, Ca, K, MgFe, Cu, Co, Mo
Photosynthesis
A TYPICAL PLANT
Glycolysis
bacteria
H2O
(daytime)
Respiration(nighttime)
PRIMARY METABOLISMPRIMARY METABOLISM
Primary metabolism comprises the chemical processesthat every plant must carry out every day in order tosurvive and reproduce its line.
PhotosynthesisGlycolysisCitric Acid CycleSynthesis of amino acidsTransaminationSynthesis of proteins and enzymesSynthesis of coenzymesSynthesis of structural materialsDuplication of genetic materialReproduction of cells (growth)Absorption of nutrients
SECONDARY METABOLISMSECONDARY METABOLISM
Secondary metabolism comprises the chemical processesthat are unique to a given plant, and are not universal.
Secondary metabolism is the chemistry that leads to the formation of a natural product.
Sometimes portions of this chemistry are common to a numberof different plants or plant families, but the actual chemicalproduced (natural product) is usually different in one plant than in another.
Common chemical precursors can lead to different results.
Secondary metabolites (in most cases) do not appear to benecessary to the survival of the plant, but they may give it a competitive advantage.
CO2 + H2O
Photosynthesis Glucose Carbohydrates
GLYCOLYS IS
Acetyl CoA
Citric Acid Cycle
Fatty AcidsLipids
AcetogeninsTerpenesSteroids
Building Blocks
Amno Acids
Proteinssynthesis
enzymes
regulationNucleicAcids
reproduction
Alkaloids
Phenyl-propanoids
RNA DNA
PRIMARY METABOLISMPRIMARY METABOLISM
SECONDARYSECONDARYMETABOLISMMETABOLISM
SECONDARYSECONDARYMETABOLISMMETABOLISM
h
CO2 + H2O + ATP
Flavonoids
PolysaccharidesGlycosidesNucleic Acids
Shikimate pathwayAromatic CompoundsLignans
aromatic amino acidsaliphatic amino acids
CH3COSCoA
CH3COSCoA
(photosynthesis)
phosphoenol pyruvate
pyruvate
acetylCoA CH3COSCoA
-O2CCH2COSCoA
CH3COSCoA
Polyketides, Fatty Acids Prostaglandins, Macrocyclic Antibiotics
Shikimate
CH3COCH2COSCoA
mevalonate
Isoprenoids (terpenes,steroids, carotenoids)
AlkaloidsPeptidesPenicillinsCyclic Peptides
CITRICACIDCYCLE
(3)
(3) Mevalonate Terpenes, Steroids
-- made from 5-carbon units
-pinene (C10) cholesterol (missing 3 C’s)
phytane (C20)
(3) Isoprene pathway: Terpenes
- C6 compound that loses CO2
to form C5 units
Isoprene Biosynthesis
DMAP IPP
- Result: two isomeric 5-carbon molecules, IPP + DMAP
- Pyrophosphates: high-energy group powers biosynthetic rxns.. “nature’s leaving group”
decarboxylates to yield IPP
Parents Compounds and Type
………white board !.……..
Biosynthesis of Monoterpenes (C10)
rearranged to form sesquiterpenes (C15)
Geranyl pyrophosphate (C10)
Farnesyl pyrophosphate (C15)
Prenyl transferase +
DMAP IPP
-OR-
Cyclase enzymes
cyclic monoterpenes (C10)
…White board….
Fig. 24.07
Biosynthesis of Monoterpenes (C10)
(1) DMAP ionizes to form electrophilic carbocation
(2) Nucleophilic attack by IPP forms geranyl-PP
(3) Stereospecific loss of HR, forming double bond
(4) Geranyl-PP ionizes, rearranges to form a carbocation intermediate
- Cyclic monoterpenes then form via enzyme-catalyzed stereospecific rearrangements, functionalizations
Monoterpenes
thujone
Overview of isoprenoid biosynthesis and the role of prenyltransferase in higher plants
Overview of isoprenoid biosynthesis and the role of prenyltransferase in higher plants
Abbreviations:IPP:IsopentenyldiphosphateDMAPP:DimethylallyldiphosphateFPP:FarnesyldiphosphateGGPP:GeranylgeranyldiphosphateGPP:GeranyldiphosphateOPP:Diphosphate moisty
Mechanism of acyclic monoterpene synthaseMechanism of acyclic monoterpene synthase
(+)-carvone = caraway seed(-)-carvone = spearmint
(+)-limonene = oranges(-)- limonene = lemons
Most cyclic monoterpenes have a distinctive odor - basis of perfume & flavor industries
Stereoisomers have different characteristic smells - demonstrates that smell receptors are 3D proteins, i.e. chiral environments that can distinguish enantiomers
Biosynthesis of Sesquiterpenes (C15)
rearranged to form sesquiterpenes (C15)
Geranyl pyrophosphate (C10)
Farnesyl pyrophosphate (C15)
Prenyl transferase +
DMAP IPP
Biosynthesis of Sesquiterpenes (C15)
rearranged to form sesquiterpenes (C15)
Geranyl pyrophosphate (C10)
Farnesyl pyrophosphate (C15)
Prenyl transferase +
DMAP IPP
- if you introduce a labeled carbon in the precursor, you can see where it ends up in the final natural product
Biosynthesis of Sesquiterpenes (C15)
rearranged to form sesquiterpenes (C15)
Geranyl pyrophosphate (C10)
Farnesyl pyrophosphate (C15)
Prenyl transferase +
DMAP IPP
- if you introduce a labeled carbon in the precursor, you can see where it ends up in the final natural product
Reaction mechanism of all SesquiterpenesReaction mechanism of all Sesquiterpenes
Reaction mechanism of all SesquiterpenesReaction mechanism of all Sesquiterpenes
Diterpene (C20) Biosynthesis
Farnesyl pyrophosphate (C15)
+
Gerenylgerenyl-PP (C20) carbocationintermediate
Diterpenes
Gibberellin Biosynthesis
CH3 oxidized, then lost as CO2
Gibberellin A3, a potent C19 plant hormone
- found in most plants (though originally isolated from a fungus)
Diterpenes
DMAP IPP
Squalene (from shark oil)
C30 compound: 2 farnesyl’s joined tail-to-tail
Geranyl pyrophosphate (C10)
Farnesyl pyrophosphate (C15)
Triterpene (C30) Biosynthesis
Triterpene (C30) Biosynthesis
Squalene
other C30 triterpenes
cholesterol (C27)
sex hormones
vitamin D
Cholesterol Biosynthesis
- lose 3 methyl groups
19 steps
Vitamin D Biosynthesis
- cholesterol from liver is transported to skin
- photochemically converted into vitamin D- vitamin allows uptake
of essential calcium
cholesterol24-ethylcholesterol
24-stigmasterolgorgosterol
dinosterol 3-methoxycholesterol
Higher terpenes (C40)
Lycopene
2 x geranyl geranyl-PP
- major antioxidant pigment in tomatoes
-carotene- major accessory pigment in photosynthesis
The color of an egg yolk is from the xanthophyll carotenoids lutein and zeaxanthin
Violaxanthin is a natural xanthophyll pigment with an orange color found in a variety of plants including pansies. It is biosynthesized from zeaxanthin by epoxidation.[1] As a food additive it used under the E number E161e as a food coloring; it is not approved for use in the EU[2] or USA however is approved in Australia and New Zealand[3] (where it is listed under its INS number 161e).
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Vitamin AVitamin A
• Occurs only in the animal world.• Found in the plant world in the form of a provitamin in a group of pigments called carotenes.
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Vitamin AVitamin A
The best understood role of Vitamin A is its participation in the visual cycle in rod cells.• the active molecule is retinal (vitamin A aldehyde), which forms an imine with an -NH2 group of the protein opsin to form the visual pigment called rhodopsin.
• the primary chemical event of vision in rod cells is absorption of light by rhodopsin followed by isomerization of the 11-cis double bond to the 11-trans configuration.
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Vitamin A and the Chemistry of Vitamin A and the Chemistry of VisionVision
Rhodopsin
Rhodopsin
Metarhodopsin II
Metarhodopsin II
The highest terpenes (Cbig #)~ 1 % of plants can synthesize cis-polyisoprenoids, like rubber
H3C
Commercially used rubber plants can convert nearly 100% of their mevalonate into rubber
Notes on Terpenes(1) Oxidation reactions are carried out by the enzyme cytochrome P450
- activate oxygen to introduce -OH, carboxyl groups- allow removal of C’s through decarboxylation
(2) Triterpenes form flexible rings (chair, boat conformations) with many chiral centers {rings usually not aromatic}
- provides a huge number of potential 3D structures- high degree of biological activity
(3) Pathways can be elucidated using labeled precursors, such as mevalonate with a 13C at position 2
- carbon NMR experiments reveal where the label ends up in the completed molecule