1. Acetate pathway
Dr. Jehad Almaliti

2. Acetate formed from carbohydrate via pyruvic acid
Produce large no. of imp. natural products (flavonoids, anthraquinones, macrolides, terpenes & steroids)
2 main routes originate with acetate pathway:
Acylpolymalonate pathway leading to FA & polyketides
Mevalonic acid pathway producing terpenes & steroids
Polyketide constitute a large class of natural products grouped together on purely biosynthetic pathways
Their diverse structures can be explained as being derived from poly-β-keto chains, formed by coupling of acetic acid (C2) units via condensation reactions
Included in such compounds are the fatty acids, polyacetylenes, prostaglandins, macrolide antibiotics and many aromatic compounds, e.g. anthraquinones and tetracyclines.

3. Fats Esters of fatty (long chain carboxylic) acids
Common are triacyl glycerols, which can be hydrolyzed (saponified) into soaps:

4. Micelles: mode of action of soap
H2O
Soap (above) can be represented as:
H2O
H2O
H2O
Soap (and detergents) form spherical clusters
(right) called micelles; micelles surround
and dissolve non-polar substances (oily
stains) and render them “soluble.”
H2O
Oil
H2O

5. Oils (polyunsaturated fats)
Presence of cis double bonds in oils makes it difficult
for the molecules to pack regularly in a solid structure;
oils have lower melting points than fats, and are liquids at RT.

6. Biosynthesis of Fatty Acids
Repetitive applications of Claisen reactions;
explains why most fatty acids have an even number of carbon atoms.
The processes of fatty acid biosynthesis are well studied and are known to be catalysed by the enzyme fatty acid synthase (FAS).
The reverse of this is the β-oxidation sequence for the metabolism of fatty acids.

7. Acylation of Malonyl Coenzyme A with 2 Carbon unit
The conversion of acetyl-CoA into malonyl-CoA increases the acidity of the α-hydrogen atoms, thus providing a better nucleophile for the Claisen condensation.

8. Decarboxylation, Reduction, Dehydration and Reduction
Acetoacetyl-CoA (β-ketoacyl-CoA)
B-Hydroxy ester
Isoniazid and Triclosan both inhibitor of bacteria ER
α,β-unsaturated ester
a saturated acyl-
Enol reductase
Inhibitors: Isoniazid and Triclosan

9. Acylation of Malonyl Co A with 4 carbon unit

10. Conversion to 6 carbon unit

11. Acylation of Malonyl Co A with 6 carbon unit

12. Conversion to 8 carbon unit...etc.

13. Common Saturated Fatty Acids
Odd carbon fatty acids?
All carbon atoms in the fatty acid originate from acetate, but malonate will only provide the C2 chain extension units and not the C2 starter group.
Natural fatty acids may contain from 4 to 30, or even more, carbon atoms, the most abundant being those with 16 or 18 carbon atoms.

14. Common Unsaturated Fatty Acids

16. Polyunsaturated Fatty Acids
Polyunsaturated fatty acids (PUFAs) include those having two and three double bonds.
Omega-3 fatty acids are those unsaturated fatty acids that have a double bond between the third and fourth carbon from the end of the carbon chain (opposite the CO2H group).
A common omega-3 fatty acid found in fish oil is linolenic acid:
Omega-3 fatty acids are considered beneficial for brain function.

17. Lipstatin and Orlistat
Pancreatic lipase inhibitor
Isolated from Streptomyces toxytricini cultures
Active moiety is the β-lactone
Tetrahydrolipstatin (Orlistat) is a synthetic analogue based on lipstaton.

18. Biogenesis of natural acetylenes
Biogenetic precursor of the acetylenic substances is oleic acid
H3C-(CH2)7-CH=CH-(CH2)7-COOH Oleic acid [18:1(9c)]
↓-2H
H3C-(CH2)4-CH=CH-CH2 CH=CH-(CH2)7-COOH Linoleic acid [18:2 ] → Linolenic acid [18:3]
H3C-(CH2)4-CΞC-CH2 CH=CH-(CH2)7-COOH Crepenynic acid (12-13 dehydrolinoleic acid)
H3C-CH2- CH2- CH2- CH= CH -CΞC-CH2 CH=CH-(CH2)7-COOH Dehydrocrepenynic acid
↓-2H ↓-2H ↓-2H
They are especially common in plants of the Compositae/Asteraceae and the Umbelliferae/Apiaceae
Further modifications:
Shortening of the side chain, oxidation, reduction, decarboxylation, ester formation, addition of “O” or “S”, elimination of the methyl group, hydrogenation,…….

19. Echinacea spp. [coneflowers] Fam. Asteraceae
(Echinacea Article Link)
North American origin;
Medicinally used three species are:
E. angustifolia
E. purpurea
E. pallida

20. Constituents and uses High MW CH/PS [echinacin, inulin, etc…]
Phenolic compounds: Caffeic acid derivatives (chlorogenic, caffeic, chicoric); some as glycosides (Echinacoside)
Pyrrolizidine alkaloids
Ployacetylene-Polyynes, some as amides (alkylamides, alkamides)
Immunostimulating effect; prevention and treatment of common cold, flu, respiratory disorders,…
Antibacterial activity against: E.coli, S. aureus, P. aeruginosa
Commercially available: Echimmune Tablets, syrup

21. Chemical structure of some secondary metabolites of E. purpurea
Echinacoside

22. Toxic polyalkyne containing plants of Apiaceae
1-Cicuta virosa (Apiaceae): European water hemlock (Cowbane)……الشكران المائي
All parts of the plant are toxic; roots very rich in acetylenic compounds
Major compound is cicutoxin (toxic compound), a reversible potassium channel blocker; other compounds: cicutol, cicudiol,..
Signs of toxicity: Profuse salivation, abdominal pain, prolonged vomiting and violent convulsions
2-Oenanthus crocata: Hemlock water dropwort; toxic compound: Oenanthotoxin.
3-Aethusa cynapium Dog parsley (poison parsley); toxic compound: Aethusin.

23. Cicutoxin
Oenanthotoxin
Aethusin

24. Important Scientific Note:
The majority of the Umbelliferae (Apiaceae) family are harmless. These include species of celery, parsley, parsnip, and carrots. The poisonous members are hemlock (Conium maculatum, poison hemlock), cowbane (Cicuta virosa, water hemlock), and hemlock water dropwort (Oenanthus crocata).
Cicuta virosa

25. Acetylenes from microorganism
Mycomycin: a highly unsaturated antibiotic acid C13H10O2  obtained from an actinomycete of the genus Nocardia (N. acidophilus)
Very thermolabile
Complete retention of activity by storage at temp. -40o or lower
Soluble in alcohol, ether, DCM
Forms water-soluble Na-salts
(3E,5E)-3,5,7,8-Tridecatetraene-10,12-diynoic acid

26. Aromatic Polyketides
Condensation of acetate-derived C2 units produce polyketo-acid (poly-keto-methylene-chain, β-Ploy-keto Acid)
Following dehydration, a chain of polyketo-acid contains 4 or more acetate units, cyclize in 5 different ways producing benzene or pyrone rings
Important ones are: Orsellinic acid type and phloroacetophenone type monocyclic compounds, which in turn are further modified

27. Benzene and Pyrone rings formed from a β-Ploy-keto Acid

28. Formation of monocyclic aromatic compounds

29. Formation of orsellinic acid