1. Chapter 27. Biomolecules: Lipids
Based on McMurry’s Organic Chemistry, 6th edition
©2003 Ronald Kluger
Department of Chemistry
University of Toronto

2. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
About Lipids
Naturally materials that preferentially extract into nonpolar organic solvents
Includes fats, oils, waxes, some vitamins and hormones, some components of membrane
General types: esters (“saponifiable”) and those that can’t be hydrolyzed
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

3. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
27.1 Waxes, Fats, and Oils
Waxes - contain esters formed from long-chain (C16-C36) carboxylic acids and long-chain alcohols (C24-C36)
Triacontyl hexadecanoate is in beeswax
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

4. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
Fats and Oils
Animal fats and vegetable are triacylglycerols oil
Triesters of glycerol with three long-chain carboxylic acids
Saponification of a fat or oil with (reaction with aqueous NaOH) yields glycerol and three fatty acids
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

5. Fatty Acids (from Fats and Oils)
Straight-chain (C12 - C20) carboxylic acids
Double bonds are cis-substituted but trans-fatty acid also occur
A fat or oil in nature occurs as a mixture of many different triacylglycerols
The most abundant saturated fatty acids are palmitic (C16) and stearic (C18)
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

6. Unsaturated and Polyunsaturated Fatty Acids
Oleic (C18 with one C=C) and linolenic (C18 with 3 C=C) are the most abundant unsaturated
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

7. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
27.2 Soap
A mixture of sodium or potassium salts of long-chain fatty acids produced by alkaline hydrolysis (saponification) of animal fat with alkali
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

8. Cleansing Action of Soap
The carboxylate end of the long-chain molecule is ionic and therefore is preferentially dissolved in water
The hydrocarbon tail is nonpolar and dissolves in grease and oil
Soaps enable grease to be dissolved into water
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

9. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
Detergents
“Hard” water contains Mg+2 and Ca+2 that form insoluble salts with soaps
Synthetic detergents are alkylbenzene sulfonates that dissolve dirt like soaps but do not form scums with Mg+2 and Ca+2 .
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

10. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
27.3 Phospholipids
Phospholipids are diesters of H3PO4, phosphoric acid
Phosphoric acid can form monoesters, diesters and triesters
In general these are known as “phosphates”
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

11. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
Phosphoglycerides
Contain a glycerol backbone linked by ester bonds to two fatty acids and phosphoric acid
Fatty acid residues with C12–C20
The phosphate group at C3 has an ester link to an amino alcohol
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

12. Phosphoglyceride Membranes
Phosphoglycerides comprise the major lipid component of cell membranes
Nonpolar tails aggregate in the center of a bilayer
Ionic head is exposed to solvent
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

13. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
Sphingolipids
The other major group of phospholipids
Sphingosine or a dihydroxyamine backbone
Constituents of plant and animal cell membranes
Abundant in brain and nerve tissue, as coating around nerve fibers.
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

14. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
27.4 Prostaglandins
C20 lipids that contain a five-membered ring with two long side chains
Present in small amounts in all body tissues and fluids
Many physiological effects
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

15. Prostaglandin Sources
Biosynthesized from arachidonic acid (C20 unsaturated fatty acid)
Catalyzed by cyclooxygenase (COX)
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

16. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
27.5 Terpenoids
Steam distillation of plant extracts produces “essential oils”
Chemically related to compounds in turpentine (from pine sap) called terpenes and thus called terpenoids
Mostly hydrocarbons (some oxygens) that do not contain esters (stable to hydrolysis)
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

17. Terpenoids Are Isoprenoids
Terpenoid structures are derived from isoprene (2-methyl-1,3-butadiene) units connected head-to-tail (Isoprene Rule)
The term “head-to-tail” means that dissimilar ends are connected (you can choose which is a “head” and which is a “tail”)
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

18. Classification of Terpenoids
Classified according to the number of di-isoprenoid (C10) units they contain
Monoterpenes have 10-carbons, sesquiterpenes (sesqui = 1 1/2) have 15-carbons from three isoprene units, and so on
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

19. Some Important Terpenoids
The triterpene lanosterol is the precursor of steroid hormones
The tetraterpene b-carotene is a source of vitamin A
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

20. 27.6 Biosynthesis of Terpenoids
Isopentenyl pyrophosphate (IPP) forms higher isoprenoids in reactions catalyzed by prenyl transferase
Monoterpenoids, diterpenoids, and tetraterpoids arise from 1-deoxyxylulose 5-phosphate.
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

21. Mevalonate Pathway to Isopentenyl Diphosphate
Begins with the conversion of acetate to acetyl CoA followed by Claisen condensation to yield acetoacetyl CoA
Catalyzed by acetoacetyl-CoA acetyltransferase
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

22. Aldol Condensation Produces HMG-CoA
Carbonyl condensation reaction of acetoacetyl CoA with acetyl CoA
Produces 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

23. Reduction Forms Mevalonate
HMG CoA is reduced to mevalonate
Catalyzed by HMG CoA reductase utilizing NADPH
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

24. Conversion of Mevalonate to IPP
Pyrophosphorylation gives mevalonyl-PP
Addition of phosphate from ATP followed by loss of CO2 and phosphate
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

25. Conversion of Isopentenyl Diphosphate to Terpenoids
For triterpenes and larger, head-to-head coupling of farnesyl diphosphates gives squalene
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

26. Mechanism of Isomerization
Isomerization of IPP to DMAPP is catalyzed by IPP isomerase through a carbocation pathway
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

27. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
Coupling Mechanism
Nucleophilic substitution reaction in which the double bond of IPP behaves as a nucleophile in displacing diphosphate ion leaving group (PPO)
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

28. Conversions of Monoterpenoids
Typically involves carbocation intermediates and multistep reaction pathways catalyzed by a terpene cyclase
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

29. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
27.7 Steroids
Steroids,are another class of nonsaponifiable lipid, defined by structure
Has four fused rings A, B, C, and D, beginning at the lower left
Carbon atoms are numbered beginning in the A ring
The six-membered rings are in fixed chair conformations
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

30. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
Functions of Steroids
In humans as hormones, steroids are chemical messengers secreted by glands and carried through the bloodstream to target tissues
Also widely distributed as cholesterol
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

31. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
Male Sex Hormones
Testosterone and androsterone are the two most important male sex hormones, or androgens
Androstanedione is a precursor
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

32. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
Female Sex Hormones
Estrone and estradiol are the two most important female sex hormones, or estrogens
Progesterone is the most important progestin, steroids that function in pregnancy
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

33. Adrenocortical Hormones
Adrenocortical steroids: secreted by the adrenal glands near the upper end of each kidney
Mineralocorticoids: control tissue swelling by regulating cellular salt balance
Glucocorticoids: regulation of glucose metabolism and in the control of inflammation
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

34. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
Synthetic Steroids
Made in pharmaceutical laboratories as new drugs
Includes oral contraceptives and anabolic agents
Methandrostenolone is an anabolic steroid used for tissue-building
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

35. 27.8 Stereochemistry of Steroids
Two cyclohexane rings can be joined in either a cis or a trans manner
In cis-decalin, both groups at the ring-junction positions are on the same side of the two rings
In trans-decalin, the groups at the ring junctions are on opposite sides
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

36. A/B Junction in Steroids
Steroids can have either a cis or a trans fusion of the A and B ring
(B–C and C–D) are usually trans
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

37. Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003
27.9 Steroid Biosynthesis
Enzyme-catalyzed addition of oxygen atom to squalene
Stereospecific formation of an oxirane from an alkene
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003

38. Cyclization to Steroid
Stork-Eschenmoser mechanism
Enzyme-catalyzed
See Figure 27.6
Based on McMurry, Organic Chemistry, Chapter 27, 6th edition, (c) 2003