Organic Chemistry II

Chapter 3 Lipids

LIPIDS- Introduction Characteristics of Lipids

Composed of Carbon, Hydrogen, and Oxygen Greater than 2:1 ratio of H:O Includes fats, oils, phospholipids, and cholesterol Building blocks are fatty acids and glycerol. Energy storage molecules Phospholipids part of cell membrane

LIPIDS- Introduction
Non polar compounds Insoluble in water, but soluble in an organic solvent (e.g., ether, benzene, acetone, chloroform) Form long-chain hydrocarbon groups (carbon and hydrogen) but may also contain oxygen, phosphorus, nitrogen and sulfur. Consist of liquid and solid Synonymous with fat, but also includes phospholipids, sterols, etc.

Types of Lipids
The majority forms molecules such as waxes, triacylglycerols, phospholipids and glycolipids. Other substances are also considered as lipids while belonging to other classes of molecules, e.g. fat soluble vitamins (A, D, E and K), coenzymes (ubiquinones), pigments (carotenoids), terpenes, phenolics and sterols. (They are equally considered because they are extracted with the cellular or membrane constituents by extraction with fat solvents)

Fatty Acid Structure

Carboxyl group (COOH) forms the acid. R group is a hydrocarbon chain.

Fatty Acids and Triacylglycerols

The fatty acids are long-chain (usually unbranched) carboxylic acids that get their name from their source, the easily extracted fats of plant and animal origin. The fats are esters of the fatty acids with the triol glycerol, and most fatty acids can only be obtained by hydrolysis of their parent fats.
O O C R O 1) aq. HO-, O heat C R' 2) H3O+ OH OH O R C OH O R' C OH O R'' C OH

O O C R'' triacylglycerol (glyceryl trialkanoate)

OH glycerol (1,2,3-propanetriol)

Rarely, as in the case of the fat from nutmeg, all of the R groups are alike (in this case, they are all unbranched C13 alkyl groups), but commonly they are of two or three types. Fatty acids nearly always have an even number of carbon atoms because the chains are assembled from the simple two-carbon precursor, acetic acid. The most common fatty acids contain 16 or 18 carbon atoms.

Fatty Acid Structural Variation

The most common variation is in the degree of saturation of the fatty acid. Olive oil on hydrolysis yields predominantly oleic acid, which contains one double bond in the middle of its straight-chain C18 skeleton; its systematic name is cis-9-octadecenoic acid.
9

COOH

Oleic acid Other unsaturated fatty acids often have two or more alkene-type double bonds. In mono- and polyunsaturated acids, the double bonds are cis (remarkable since that is the less stable configuration). The first double bond is commonly between C9 and C10, and additional double bonds are separated by single methylene groups, as in linolenic acid, the predominant fatty acid from linseed (flax) oil.
15 9

COOH

cis, cis, cis-9,12,15-Octadecatrienoic acid A methylene group that links two double bonds, like the two in this acid, is very susceptible to oxidative attack by free radicals. This can lead to rancidity or, as here, to polymerization to traditional varnish.
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Fats, Oils, and Hydrogenation

Triacylglycerols that have melting points above room temperature are called "fats," lower melting triacylglycerols are "oils." Oils have lower MP's because they incorporate a higher content of unsaturated fatty acids, which with their bent molecules and lower flexibility do not so readily find their place in a crystal lattice (or organized-phase fat). Because there is handling (and marketing) advantage in fats vs. oils, many oils are subjected to partial hydrogenation. The aim is to achieve enough saturation to raise the MP but not to give up an unnecessary degree of unsaturation, which would yield an excessively hard fat and lose the nutritional advantage attributed to unsaturated fats. The hydrogenation is done at 20-40 psi hydrogen pressure, 175-190 oC, and with use of Raney nickel catalyst. Typical commercial products are the shortenings made principally from cottonseed oil and the peanut butters that do not separate on standing at room temperature. During the course of partial hydrogenation, some cis double bonds rearrange to the more stable trans configuration and some migrate to new locations. This appears to be associated with increased risk of cardiovascular disease, and efforts are being made to reduce the content of these rearranged fats in food products.

Fatty Acids long chain linear hydrocarbons carboxylic acids Usually have an even number of C atoms (usually 12 to 20) The carbons are numbered starting from the carboxylic C. They are amphiphilic; they have a polar end and rest of the molecule is nonpolar Fatty acids may be saturated (no double bonds) or unsaturate (one or more double bonds) All naturally occuring double bonds have a cis-configuration 2 or more double bonds exist as non-conjugated double bond Longer chain and saturation increases melting point of FA FAs are ionized at physiological pH

Classification of Lipids Fatty acids: are long chain linear (unbranched) hydrocarbon carboxylic acids Triglycerides: are fatty acid esters of glycerol Phospholipids: are lipids that contain one or more phosphate groups Glycolipids: have a carbohydrates component Eicosanoids: are a family of derivatives of Arachidonic acid Steroids: have a basic structure of a perhydrocyclopentanophenanthrene ring system Lipoproteins: are complexes of lipids and proteins that circulate in the blood.

Saturated fatty acid the carbon atoms are saturated with hydrogen; meaning they are bonded to as many hydrogens as possible. Mono unsaturated fatty acids a fatty acid with one double bond. Poly unsaturated fatty acids a fatty acid with more than one double bond.

Saturated and unsaturated Fatty Acids

O 2 1 CH2 C OH
O 1 C OH

8 7 CH3 CH2

5 3 4 6 CH2 CH2 CH2 CH2

8 5 3 7 4 6 2 CH3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2

8 7 CH3 CH2

5 3 4 6 CH2 CH2 CH2 CH2

O 2 1 CH2 C OH

Types of double bonds

Cis/ trans Methylene interrupted/ conjugated

Cis and trans fatty acids

methylene interrupted
The double bonds are separated from each other by a single methylene group,

Conjugated double bonds

When two double bonds are separated by one single bond, they are called conjugated double bonds.)

Glycerol

Synthesis of a Fat

Reactions of the Carboxyl Group of Fatty Acids

The fatty acids react like simpler acids, undergoing, for example, these reactions: R
in ether 2) H2O

1) LiAlH4

OH

1o alcohol
O

O OH

CH3OH, H+

methyl ester
SOCl2
in C5H5N

OCH3

O Cl

acid chloride
O O C R O O CH3OH, H+ C R' OH OH OH Glycerol O R C OCH3 O + R' C OCH3 O R'' C OCH3 Mixed fatty acid methyl esters

O O C R'' An oil or fat

Biodiesel fuel

Transesterification

Reactions of the Alkenyl Chain of Unsaturated Fatty Acids

H H CH3(CH2)nCH CH(CH2)mCOOH H2, Ni Br2 in
CCl4

Br CH3(CH2)nCH

CH3(CH2)n

(CH2)mCOOH

CH(CH2)mCOOH Br

1) OsO4 2) NaHSO3

OH OH CH3(CH2)nCH CH(CH2)mCOOH H CH3(CH2)nCHCHBr(CH2)mCOOH H AND CH3(CH2)nCHBrCH(CH2)mCOOH

HBr

Waxes
Manipulated as protective coating Due to water resistance properties This is because wax do not have hydrophilic part

A Phospholipid

Phospholipids
Phospholipids= lipids that contain a phosphate group A lipid consisting of a glycerol bound to two fatty acids and a phosphate group.

 Phospholipids are very much like triglycerides but with one important difference. A phosphate functional group is substituted for one of the three fatty acids.

 An alcohol headgroup is linked to glycerol at carbon 3 by phosphodiester bond.

Phospholipids contain fatty acids linked to glycerol by ester bonds at carbons 1 and 2
Fatty acyl chains can be saturated or unsaturated A typical phospholipid arrangement is the presence of a saturated fatty acid at the C1, and an unsaturated or polyunsaturated fatty acid at C2

Amphiphile
Hydrocarbon part of phospholipid are non polar, while the phosphate and amino alcohol part contain charged group, thus polar

So phospholipid have amphiphilic character

What is amphiphilic character?

Both water loving and fat loving property

Headgroups of membrane phospholipids

Choline, ethanolamine are the most abundant PL classes. Headgroup has no net charge Serine and inositol headgroups have net negative charges

Amphiphilic
The 'head' of a phospholipid is hydrophilic (attracted to water), while the hydrophobic 'tails' are repelled by water and are forced to aggregate. The hydrophillic head contains the negatively charged phosphate group, and may contain other polar groups. The hydrophobic tail usually consists of long fatty acids hydrocarbon chains.

phospholipids
Hydrophobic effect: Hydrophobic lipid tails avoid water but associate with each other, resulting in phospholipid bilayer

Terpenes
Main component in essential oil. Rubber is one of the most widely known terpenes Hormones Secondary metabolites (no apparent function in the basic processes of growth and development, but provide a number of valued functions for the living organisms that produce them) in organism eg. defense against predators, pathogens and competitors, growth inhibitors Also involve in physiological functionsfor example as building blocks, sterols

Building block of isoprene

CH2=C(CH3)CH=CH2 (C5H8)

Terpenes Isoprenes
- Building blocks of terpenes - CH2=C(CH3)-CH=CH2 (C5H8)

Terpenes
- (C5H8)n, n is the number of linked isoprene units - The isoprene units may be linked together "head to tail to form linear chains or they may be arranged to form rings.

- Classified according to number of isoprene unit

Terpenoid
- Chemically modified terpenes - Classified according to number of isoprene unit

Terpenes
Mostly are hydrocarbon (terpene), but oxygen containing compounds such as alcohol e.g menthol, aldehydes (e.g., citronellal) or ketones (terpenoid) are also found Structurally diverse as isoprene units can be assembled and modified in thousands of ways. Most are multicyclic structures that differ from one another not only in functional groups but also in their basic carbon skeletons.

The term "terpene" at times is used broadly to also include the terpenoids, sometimes referred to as "isoprenoids," which are terpenes that have been chemically modified, such as through oxidation, where methyl groups is moved or removed, or oxygen atoms added.

Terpene Classification
Class Name Monoterpene Sesquiterpene Diterpene Triterpene Isoprene Units 2 3 4 6 Carbon Number 10 15 20 30

Terpenes and Terpenoids

These compounds have long fascinated people because many have appealing aromas and come from interesting sources, mostly plants. Terpenes are hydrocarbons whose structures are assembled from five-carbon units like in isoprene: tail head Terpenoids are the derivatives that Isoprene An "isoprene unit" carry oxygen-containing groups. The terpene classes Number of carbons
Monoterpenes Sesquiterpenes Diterpenes Triterpenes 10 15 20 30

With any compound that contains multiples of five carbon atoms, the first thought is that its molecules may be constructed of C5 isoprene units, frequently, but not always, connected head to tail. Before modern instrumentation, this often provided valuable guidance. Examples of terpenes include: tail
head head tail tail head tail tail head

Myrcene
head

(a monoterpene from bay leaves)

Limonene

Zingiberene
(a sesquiterpene from ginger root)

(a monoterpene from citrus oils)

Monoterpene
2 isoprene units , molecular formula C10 H16 . e.g geraniol, limonene Most monoterpenes and sesquiterpenes are good conveyors of information due are lowmolecular-weight and high volatility. In addition, the vast structural variety of terpenes present allows messages to be very specific. Main constituents of the essential oils

Sesquiterpene
3 isoprene units , C15H24. e.g farnesenes, farnesol. (The sesqui- prefix means one and a half.)

Diterpene
4 isoprene units , C20 H32 . Commonly present in conifer resin Examples are: phytol, vitamin A1, taxadiene Also form the basis for biologically important compounds such as retinol, retinal and phytol Known to be antimicrobial , antiinflammatory.

Sesterpenes
5 isoprene units, sester- means half to three, i.e. two and a half.) e.g geranylfarnesol Quite rare in nature, occur in the protective wax of fungi and insects

Triterpenes
6 isoprene units , C30H48. E.g Squalene. Squalene is then processed biosynthetically to generate structural precursors to all the steroids.

Tetraterpenoid (Carotenoid)
8 isoprene units , C40 H64 . Occur as hydrocarbon. e.g Carotene, further oxygenated carotenes are known as xanthophyll Biologically important e.g beta-carotenes

Polyterpenes
Long chains of many isoprene units. Natural rubber. Consists of polyisoprene in which the double bonds are cis. Some plants produce a polyisoprene with trans double bonds, known as gutta- percha.

Steroids
Steroid nucleus 3 cyclohexane rings 1 cyclopentane ring

steroid nucleus

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 Characterized by having a carbon skeleton, (17 carbon), bonded to 28 hydrogen atoms. with four fused rings (made up of three hexagonal carbon rings (A,B,C) and a pentagonal carbon ring (D)

 Each steroid family differs from each other by the degree of unsaturation within the ring system and the substituents attached to the rings. These substituents are in most cases oxidized to alcohol, aldehyde , ketone, or carboxylic acid functional groups. The most common locations of functional groups are C3, C-4, C-7, C-11, C-12 & C-17. Ring A is sometimes aromatic.

There are four rings in a steroid skeleton and hence there are three fusion points. A/B, B/C and C/D rings share two carbons each (fusion).

Steroid Conformation

Conformatio n For two-ring system, the structures of cis and trans-fused rings look like this: When the two hydrogens are oriented opposite to each other with the ring system thought to as forming a plane, the ring fusion is called trans. When there are directed on the same side, it is called cis.

IUPAC Nomenclature

Nomenclature
Prefix and suffix are added. When more than one present in the same molecule, one as suffix, remainder as prefixes Suffix priority order: Carboxylic acid> lactone> ester> aldehyde> ketone> alcohol> amine> ether Halogen, nitro and alkyl always as prefixes Unsaturation indicated by the suffix ene. Location of carbon-carbon double bond is specified by giving the lesser of the two numbers in the double bond numerical prefixes such as di, tri, etc., as well as the prefixes tert- and secare ignored in alphabetizing, but the prefixes iso, neo and cyclo are considered in alphabetizing substituent groups. The hydroxyl groups have a choice of being in 2 positions, either up and termed as beta or down, termed alpha

Fat soluble vitamins

Solubility with lipid Vitamins A,D,E,K Small amounts of vitamins A, D, E and K are needed to maintain good health. Unlike water-soluble vitamins that need regular replacement in the body, fat-soluble vitamins are stored in the liver and fatty tissues, and are eliminated much more slowly than watersoluble vitamins.

 Vitamins A is a terpene, and vitamins E and K have long terpene chains attached to an aromatic moiety. The structure of vitamin D can be described as a steroid in which ring B is cut open and the remaining three rings remain unchanged.