CHAPTER 23 LIPIDS

23.1 INTRODCTION

Lipids are compounds of biological origin that dissolve in nonopoler solvents.

Lipids are defined by the physical operation that we use to isolate them.

Lipids include a variety of structure types, For example

H2C

HC

H2C

O C R

O C R'

O C R''

O

O

O

CH3

OH

CH(CH3)2

CH2OH

CH3 CH3

CH3

CH3

A fat or oil (ÓÍ»òÖ¬£©

Menthol(±¡ ºÉ´¼)

Vitamin A(άÉúËØ A£©

H2C

HC

H2C

O C R

O C R'

O P OCH2CH2N+(CH3)3

O

O

O

O-

H

HH3C

H3C

H

H

H

HO

CH3

Cholesterol (µ¨ ¹Ì ´¼)

lecithin(ÂÑÁ×Ö¬)

23.2 FATTY ACIDS AND TRIACYLGLYCEROLS

Triacylglycerols are the fats and oils of plant or animal origin.

Oils: Triacylglycerols that are liquids at room temperature. Fats: Triacylglycerols that are solids at room temperature.

Same triacylglycerols: all three acyl groups in triacylglycerols are the same. mixed triacylglycerols: the acyl groups in triacylglycerols are different.

Hydrolysis of a fat or oil produced a mixture of fatty acids.

H2C

HC

H2C

O C R

O C R'

O C R''

O

O

O

A fat or oil (ÓÍ»òÖ¬£©

H2C

HC

H2C

OH

OH

OH

+

RCOOH

R'COOH

R''COOH

(1) OH- / H2O, heat

(2) H3O+

Glycerol( ±ûÈý́ ¼)

Fatty acids(Ö¬·¾Ëᣩ

Most of fatty acids have unbrached chains and they have an even number of carbon atoms.

The double bonds in unsaturated fatty acids are all cis and not conjugated. Many naturally occurring fatty acids contain two or three double bonds. Triple bond rarely occur in fatty acids.

Saturated fatty acids have relatively high points and unsaturated fatty acids have relatively low points.

Triacylglycerols made up of large saturated fatty acids have high melting points and are solid in room temperature, vice versa.

23.2A HYDROGENATION OF TRIACYLGLYCEROLS

Solid commercial cooking fats are manufactured by partialhydrogenation of vegetable oils. Completed hydrogenationof the oil is very hard and brittle. One commercial advantageof partial hydrogenation is to give the fat a longer shelf-life.

23.2B BIOLOGICAL FUNCTION OF TRIACYLGLYCEROLS

The primary function of triacylglycerols in animal is as an energy reserve.

All of the saturated triacylglycerols of the body, and some of the unsaturated ones, can be synthesized from carbohydrates andproteins.

23.2C SAPONIFICATION OF TRIACYLGLYCEROLS

Alkaline hydrolysis of triacylglcerols produces glycerol and a mixture of salts of long-chain carboxylic acids.

H2C

HC

H2C

O C R

O C R'

O C R''

O

O

O

H2C

HC

H2C

OH

OH

OH

+

RCOO-Na+

R'COO-Na+

R''COO-Na+

Glycerol( ±ûÈý́ ¼)

Sodium carboxylates (ôÈËáÄÆÑΣ©

+ 3NaOHH2O

These salts of long-chain carboxylic acids are soaps and this saponification reaction is the way most soaps are manufactured.

Soaps are almost completely miscible with water. Soaps micellesin water are usually spherical clusters of carboxylate ions that are dispersed throughout the aqueous phase with their negativelycharged carboxylate groups at the surface and with their nonpolar hydrocarbon chains on the interior.

Thus soap solution are able to separate the dirt particles because their hydrocarbon chains can “dissolve” in the oil layer.

Synthetic detergents function in the same way as soaps; they havelong nonpolar alkane chains with polar groups at the end.

CH3(CH2)nCH2SO2O-Na+ CH3(CH2)nCH2OSO2O-Na+

CH(CH2)nCH2CH3+Na-OO2S

CH3

Sodium alkylbenzenesulfonates (Íé»ù±½»ÇËáÄÆÑΣ©

Sodium alkyl sulfates (Íé»ùÁòËáÄÆÑΣ©

Sodium alkanesulonates (Íé»ù»ÇËáÄÆÑΣ©

Synthesis of detergents offer an advantage over soaps; they function well in “hard” water.

23.2D REACTIONS OF THE CARBOXYL GROUP OF FATTY ACIDS

Fatty acids undergo reactions typical of carboxylic acids.they reactwith LiAlH4 to form alcohols, with alcohols and mineral acid toform esters, with thionyl chloride to form acyl chlorides:

RCH2COOH

(1)LiAlH4, diethyl ether

(2) H2O

CH3OH, H+

SOCl2Pyridine

RCH2CH2OH

RCH2COOCH3

RCH2COCl

23.2E REACTIONS OF THE ALKYL CHAIN OF SATURATED FATTY ACIDS

Fatty acids undergo specific halogenation when they are treatedwith bromine or chlorine in the presence of phosphorus.

RCH2COOH +(1) X2, P4

(2) H2ORCHXCOOH + HX

23.2F REACTIONS OF THE ALKENYL CHAIN OF UNSATURATED FATTY

The double bonds of the carbon chains of fatty acids undergo characteristic alkene addition reactions.

CH3(CH2)nCH=CH(CH2)mCO2H

H2

Ni

Br2CCl4

(1) OsO4(2) NaHSO3

HBr

CH3(CH2)nCH2 CH2(CH2)mCO2H

CH3(CH2)nCHBrCHBr(CH2)mCO2H

CH3(CH2)nCHOH CHOH(CH2)mCO2H

CH3(CH2)nCH2CHBr(CH2)mCO2H

CH3(CH2)nCHBrCH2(CH2)mCO2H+

23.3 TERPENES AND TERPENOIDS

Hydrocarbons known generally as terpenes and oxygen-containingcompounds called terpenoids are the most important constitutentsof essential oils.

Most terpenes have skeletons of 10,15,20 or 30 carbon atoms and are classified in the following way.

10

15

20

30

Monoterpenes

Sesquiterpenes

Diterpenes

Triterpenes

Recognition of the isoprene unit as a component of the structure of terpenes has been a great aid in elucidating their structures.

Many terpenes also have isoprene units linked in rings, and others(terpenoids) contain oxygen.

H2C

H2CCH

CH2

CHC

CH2

CCH3H3C

H2C

H2CCH

CH

C

H2CC

CH

H2C

CH3 CH2

CH

CCH3H3C

CH3

or

or

OH

Limonene(ÄûÃÊÓ;«)

-Pinene(ËÉÝÆ)

Geraniol (Ïã Ò¶́ ¼)

Menthol (±¡ ºÉ´¼)

The carotenes are tetraterpenes. They can be thought of as two diterpenes linked in tail-to-tail fashion.

CH3

CH3

CH3

CH3

H3C

H3C

CH3CH3

CH3H3C

-Carotene(ºú ÂÞ²· ËØ)

CH3

CH3

CH3

CH3

H3C

H3C

CH3CH3

CH3H3C

-Carotene(ºú ÂÞ²· ËØ)

CH3

CH3

CH3

CH3

H3C

H3C

CH3CH3

CH3H3C

-Carotene(ºú ÂÞ²· ËØ)

The catotenes all can be converted to vitamin A by enzymes in the liver.

23.3A NATURAL RUBBER

The isoprene units of natural rubber are all linked in a head-to-tailfashion and all of the bonds are cis.

CH2

H3C H

CH2

H3C

H2C CH2

H

H2C

H3C H

CH2etc etc

Narura rubber(ÌìÈ»Ï𽺣©

Pure rubber is soft and tacky, so it must be vulcanized by heatingwith sulfur. A reaction takes place that produces cross-links between the cis-polyisoprene chains and makes the robber much harder.

23.4 STEROIDS

Steroids are important “biological regulators” that nearly always show dramatic physiological effects when they are administered to living organisms.

23.4A ATRUCTURE AND SYSTEMATIC NOMENCLATURE OF STEROIDS

Steroids are derivatives of the following perhydrocyclopentanophenanthrene ring system

CH3

CH31

2

3

45

6

7

89

10

11

12

13

14 15

1617

18

19

A B

C D

RCH3

CH3

HH

12

3 45

67

8910

1112

13

1415

16

17

1819

A BC D

all ring junctions are trans

In most steroids the B, C and C, D ring junctions are trans. The A, B ring junction may be either cis or trans.

1

2

34

56

7

8910

1112

13

14 1516

17

18

19

A

BC D

A, B ring junctions is cis

RCH3

H

CH3

H

Angular methyl groups: The methyl groups that are attached at points of ring junction

β substituents: other groups that lie on the same general side of the Molecule as the angular methyl groups.

α substituents: groups that lie on the bottom.

When α and β designation are applied to the hydrogen atom at position 5,the ring system in which the A, B ring junction istrans become the 5 α series; and the ring system in which the A, B ring junction is cis becomes the 5 β series.

In systematic nomenclature of the R group at position 17 determines the base name of an individual steroid.

RHH3C

H

H

H

CH3

H

17

18

19

For example:

-H -CH2CH3

-CH(CH3)CH2CH2CH3

Androstane (ÐÛ(çÞ)Íé )

Pregnane (ÔÐÍé )

Cholane (µ¨Íé )

20 21

20 21 22 23 24

CH2CH3HH3C

H

H

H

CH3

H

17

18

19

O

5 -Pregnan-3-one (5 -ÔÐ-3-Íé £©

CH(CH3)(CH2)3CH(CH3)2HH3C

H

H

H

CH3

H

17

18

19

O

5 -Cholest-1-en-3-one(5 -µ¨ -1-Ï©-3-Íé £©

The following two examples illustrate the way these base names are used.

23.4B CHOLESTEROL

Cholesterol can be isolated by extraction of nearly all animal tissues.part of the difficulty in assigning an absolute structure to cholesterol is that cholesterol contains eight tetrahedral. For example:

C

H

HH3C

H3C

H

H

HHO

CH3

H

Cholesterol is known to serve as an intermediate in the biosynthesisof all of the steroids of the body.

23.4C SEX HORMONES

The sex hormones can be classified into three major groups:(1) The female sex hormones, or setrogens.(2) The male sex hormones, or androgens.(3) The pregnancy hormones, or progestins.

H3C

H

H

H

HO

OHH3C

H

H

H

HO

O

Estrone(´Æ¼¤ËØͪ )

Estradiol (´Æ¶þ´¼)

The first sex hormone to be isolated was an estrogen, estrone.

The examples of the second sex hormones:

H3C

H

H

H

O

OH3C

H

H

H

HO

OH

Anfrosterone (ÐÛçÞͪ )

Testosterone (غÍè ¼¤ËØ)

H

CH3 H3C

Testosterone and estradiol are the chemical compounds from which “maleness” and “femaleness” are derived. The differ of their structure is slightly.

Progesterone and norethindrone are the most important progestin.

H3C

H

H

H

O

COCH3

H3C

Progesterone (»ÆÌå ͪ )

23.4D ADRENOCORTICAL HORMONES

H3C

H

H

H

O

OH

H3C

Norethindrone (Ȳŵͪ )

C CH

At least 28 different hormones have isolated from the adrenal cortex.Included in this group are the following two steroids:

H3C

H

H

H

O

COCH2OH

H3C

Cortisone (¿ÉµÄËÉ)

OH H3C

H

H

H

O

COCH2OH

H3C

OHHO

Cortisol(Ç⻯¿ÉµÄËÉ£©

O

Most of adrenocortical steroids have an oxygen at position 11. cortisol is the major hormone synthesized by the human adrenal cortex.

23.4E D VITAMINS

The following reaction can produce vitamin D2. The photochemical reaction that takes place is one in which the dienoid ring B ofergosterol opens to produce a conjugated triene.

H3C

H

HO

H3C

H3C

H

HO

CH2UV light,room tempreature

Vitamin D2 (άÉúËØD2£©

23.4F OTHER STRUCTURE

Digitoxigenin is a cardiac aglycone that can be isolated by hydrolysis of digitalis.

Cholic acid is the most abundant acid obtained from the hydrolysis of human or oxbile.

H3C

H

H

H

HO

H3C

OH

H

H

HO

CH

H

CH3 H3C

H

OO

Digitoxigenin(ÑóµØ»Æ¶¾ÜÕÅä»ù)

HOH

HO

CH2CH2COOHH3C

Cholic acid (µ¨Ö Ëᣩ

Stigmasterol is a widely occurring plant steroid that is obeainedcommercially from soybean oil

Diosgenin is obtained from a Mexican vine, cabeza de negro,Genus Dioscorea. It is used as the starting material for a commercial synthesis of cortisone and sex hormones.

H3C

H

H

H

HO

H3C

OH

H

H

HO

CH3

H3C

O

O

CH3

H3C

Stigmasterol diosgenin(ÊíÝ÷ÔíÜÕÅä»ù)

23.4G REACTIONS OF STEROIDS

The stereochemistry of steroid reactions is often quite complex. It is strongly influenced by the steric hindrance presented at the β faceof the molecular methyl groups. But many reagent react preferentiallyrelatively at the α face (the formula on next page).

HO

CH3 H

H

O

5 ,6 -Epoxycholestan-3 -ol (only product)

HCl

HO

CH3 H

H

O

H

+

+ Cl-

6HO

CH3 H

H

OH

5

Cl

When the epoxide ring of 5 α ,6 α -Epoxycholestan-3 β -ol is opened,Attack by chloride ion must occur from the β face, but it takes place at the more open 6 position.

H3C

H

H

HHO

CH3

H2, Pt

C6H5COOOH

(1) THF: BH3(2) H2O2, OH-

HO

CH3 H

H

H3

4

5

6HO

CH3 H

H

O

5

HO

CH3 H

H

HOH

5 -Cholestan-3 -ol (85-95%)

5 ,6 -Epoxycholestan-3 -ol (only product)

5 -Cholestane-3 ,6 -diol (78%)

Cholesterol (µ¨ ¹Ì ´¼)

The relative openness of equatorial groups also influences the stereochemical course of steroid reactions.

HO

H H

CH3

OH

H3

4

56

C2H5OOCO

H H

CH3

OH

HC2H5OCOCl

(excess)

23.5 PROSTAGLANDINS

Prostagkandins are C20-carboxylic acids that contain a five-membered ring, at least one double bond, and several oxygen-Containing functional groups. Two of the active prostaglandinsare prostaglandin E2 and prostaglandin F1α.

56CO2H

CH3

O

HO HOH

H

9

11 15

1

20 CH3

HO

HO HOH

HCO2H

Prostaglandin E2 (Ç°ÁÐÏÙËØ E2)

Prostaglandin F1 (Ç°ÁÐÏÙËØ E2)

The biosynthesis of prostaglandins of the 2 series begins with aC20 polyenoic acid, arachidonic acid.

CO2H

CH3

Arachidonic acid (»¨ ÉúËÄÏ©Ëá)

2O2cyclooxygenase

CO2H

CH3

O

OH

O2H

H

(»· ×´ÄÚ¹ý Ñõ»¯Îï £©

PGC2

several steps PGE2 and other prostalandins

23.6 PHOSPHOLIPIDS AND CELL MEMBRANES

Most phospholipids acid are structurally derived from a glycerolderivative known as a phosphatidic acid.

CH2OCOR

CHOCOR'

CH2 O P OH

OH

O

From fatty acid

From phosphoric acid

23.6A PHOSPHATIDES

In a phosphatidic acid, two hydroxyl groups of glycerol are joined

in ester linkages to fatty acids and one terminal hyfroxyl group is

joined in an ester linkage to phosphoric acid.

In phosphatides, the phosphate group of a phosphatidic acid is boundthrough another phosphate ester linkage to one of the following nitrogen-containing compounds.

HOCH2CH2N+(CH3)3 HO- HOCH2CH2NH2

HOCH2

NH3+

H

CO2-

Choline (µ¨¼ï)

2-Aminoethanol (2-°±»ùÒÒ́¼)

L-Serine(L-Ë¿°±Ëá)

The most important phosphatides are the lecithins, cephalins, phosphatidyl serines, and plasmalogens.

H2C

HC

H2C

O C R

O C R'

O P OCH2CH2N+(CH3)3

O

O

O

O-

Lecithins (ÂÑÁ×Ö¬)

H2C

HC

H2C

O C R

O C R'

O P OCH2CH2NH3+

O

O

O

O-

Cephalins (ÄÔÁ×Ö¬)

H2C

HC

H2C

O C R

O C R'

O P OCH2CHNH3+

O

O

O

O-CO2

-

H2C

HC

H2C

OR

O C R'

O P OCH2CH2NH3+

O

O

O-

Plasmalogen (ËõÈ©Á×Ö¬)

phosphatidyl serines (Á×Ö¬õ£Ë¿°±Ëá)

Like soaps and detergents phosphatides “dissolve” in aqueous mediaby forming micelles.

The hydrophilic and hydrophobic portion of phosphaides form a portion of a structure unit that creates an interface between an organic and an aqueous environment.

23.6B DERIVATIVES OF SPJINGODINE

Another important group of lipids is derived from sphingosine.

On hydrolysis, sphingomyelins yield sphingosine, choline, phosphoric acid, and a C24 fatty acid called lignoceric acid.

H3C(H2C)12 H

CHOHH

CHNH2

CH2OH

H3C(H2C)12 H

CHOHH

CHNHCO(CH2)22CH3

CH2OPOCH2CH2N+(CH3)3

O

O

Sphingosine (ÇÊ°±´¼)

Sphingomyelin (ÇÊÁ×Ö¬)

23.7 WAXES

Most waxes are esters of long-chain fatty acids and long-chainalcohols. Waxes are found as protective coatings on the skin,fur, or feathers of animals, and on the leaves and fruits of plants.