Terpenoids•  Theodorofafreshlycrushedmintleaf,likemanyplantodors,isdueto

thepresenceintheplantofvola7leC10andC15,compounds,whichare

calledterpenes.

•  Terpenoids are compounds derived from a combination of two

or more isoprene units. Isoprene is a five carbon unit,

chemically known as 2-methyl-1,3-butadiene.

•  According to the isoprene rule proposed by Leopold Ruzicka,

terpenoids arise from head-to-tail joining of isoprene units.

Carbon 1 is called the ‘head’ and carbon 4 is the ‘tail’.

•  For example, myrcene is a simple 10-carbon-containing

terpenoid formed from the head to-tail union of two isoprene

units as follows1

Classifica7on•  Terpenoidsareclassifiedaccordingtothenumberofisopreneunitsinvolvedintheforma7onofthese

compounds.

2

3

CH2

CH2CH2

C

CC

CH3CH3

CHCH

CCH

CHCH

CCH

CHCH

CHC

CHCH

CHC

CHCH

CC

CH2

CH2CH2

CCH3

CH3 CH3CH3 CH3

CH3CH3

CH3

β-carotene

CH2

CH2C

CH

CH2CH

CCH2CH3

CH3

Limonene

(skin of citrus fruits)

CH2

CH2CH2

CHC

CH2

CH3

C

CC

CH2

CH2CH2

CH2

CH3

H

α-Selinene

CH2

CH2

CH

C

CC

CH2

OCH3

CH3CH3

Camphor

(Camphor tree)

4

•  TerpenoidBiosynthesis•  Whilewecaniden0fyisopreneunitswithinaterpenoidstructureandusethatinitsclassifica0on,thebuildingblockforterpenoidsynthesisinnatureisisopentenyldiphosphate(formerlycalledisopentenylpyrophosphateandabbreviatedIPP).TherearetwomajorroutestothesynthesisofIPP;namely(1)themevalonatepathwayand(2)the1-deoxyxylulosepathway.

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6

7

MevalonatePathwayStep1-ClaisenCondensa0onAnearlystepinthebiosynthesisofcholesterolandother‘isoprenoid’compoundsisaClaisencondensa0onbetweentwoacetylCoAmolecules.Anini0altrans-thioesteraseprocesstransferstheacetylgroupofthefirstacetylCoAtoanenzyma0ccysteine(Reac0on1).IntheClaisencondensa0onphaseofthereac0on,thealpha-carbonofasecondacetylCoAisdeprotonated,forminganenolate(Reac0on2).TheenolatecarbonaUackstheelectrophilicthioestercarbon,formingatetrahedralintermediate(Reac0on3)whichquicklycollapsestoexpelthecysteinethiol(Reac0on4)andproduceacetoacetylCoA.

•  tep2-AldolCondensa7on•  AcetylCoAthenreactswiththeacetoacetylCoAinanaldol-likeaddi0on.Subsequenthydrolysisproduces(3S)-3-hydroxy-3-methylglutarylCoA(HMG-CoA).

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Step3-Reduc7onoftheThioesterThethioesterisreducedfirsttoanaldehyde,thentoaprimaryalcoholbytwoequivalentsofNADPHproducing(R)-mevalonate.Theenzymecatalyzingthisreac0onisthetargetofthesta0nfamilyofcholesterol-loweringdrugs.

9

Genera0ng(R)-Mevalonate

Step4-MevalonatePhosphoryla7onTwophsophoryla0onsbyadenosinetriphosphate(ATP)occurattheterminalhydroxyl/phosphorusgroupthroughnucleophilicsubs0tu0on,followedbyathirdATPphosphoryla0onoftheter0aryhydroxylgroup.

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Step5-Decarboxyla7onFinallyisopentenyldiphosphate(IPP),the'buildingblock'forallisoprenoidcompounds,isformedfromadecarboxyla0on-elimina0onreac0on.

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Classifica7onofTerpenoids•  Mostnaturalterpenoidhydrocarbonhavethegeneralformula(C5H8)n.Theycanbeclassifiedonthebasisofvalue

ofnornumberofcarbonatomspresentinthestructure.•  Eachclasscanbefurthersubdividedintosubclassesaccordingtothenumberofringspresentinthestructure:i)AcyclicTerpenoids:Theycontainopenstructure.ii)MonocyclicTerpenoids:Theycontainoneringinthestructure.iii)BicyclicTerpenoids:Theycontaintworingsinthestructure.iv)TricyclicTerpenoids:Theycontainthreeringsinthestructure.v)TetracyclicTerpenoids:Theycontainfourringsinthestructure.

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A)MonoTerpenoids:

i)AcyclicMonoterpenoids ii)Monocyclicmonoterpenoid

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A)MonoTerpenoids:•  iii)Bicyclicmonoterpenoids:Thesearefurtherdividedintothreeclasses.

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a)Containing-6+3-memberedrings b)Containing-6+4-memberedrings.

c)Containing-6+5-memberedrings.

B)Sesquiterpenoids:

•  i)Acyclicsesquiterpenoids ii)Monocyclicsesquiterpenoids iii)Bicyclicsesquiterpenoids.

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C)Diterpenoids:i)  Acyclicditerpenoids

ii)Monocyclicditerpenoids:

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Isola7onofmonoandsesquiterpenoids•  Bothmonoandsesquiterpenoidshavecommonsourcei.eessen7aloils.Their

isola7oniscarriedoutintwosteps:

i) Isola7on of essen7al oils from plant parts: The plants having essen0al oils

generally have the highest concentra0on at somepar0cular 0me. Therefore beUer

yieldofessen0aloilplantmaterialhave tobecollectedat thispar0cular0me.e.g.

Fromjasmineatsunset.Therearefourmethodsofextrac0onsofoils.

a)Expressionmethod

b)Steamdis0lla0onmethod

c)Extrac0onbymeansofvola0lesolvents

d)Adsorp0oninpurifiedfats

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Isola7onofmonoandsesquiterpenoids•  Steamdis0lla0onismostwidelyusedmethod.Inthismethodmaceratedplant

materialissteamdis0lledtogetessen0aloilsintothedis0llateformtheseare

extractedbyusingpureorganicvola0lesolvents.Ifcompounddecomposesduring

steamdis0lla0on,itmaybeextractedwithpetrolat50˚C.Aderextrac0onsolvent

isremovedunderreducedpressure.

ii)Separa7onofTerpenoidsfromessen7aloil:Anumberofterpenoidsarepresentin

essen0aloilobtainedfromtheextrac0on.Definitephysicalandchemicalmethodscan

beusedforthesepara0onofterpenoids.Theyareseparatedbyfrac0onaldis0lla0on.

Theterpenoidhydrocarbonsdis0lloverfirstfollowedbytheoxygenatedderiva0ves.

Morerecentlydifferentchromatographictechniqueshavebeenusedbothforisola0on

andsepara0onofterpenoids.

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Generalproper7esofTerpenoids

1.Mostof the terpenoidsarecolourless, fragrant liquidswhichare lighter thanwaterandvola7lewith

steam.Afewofthemaresolidse.g.camphor.Allaresoluble inorganicsolventandusually insoluble in

water.Mostofthemareop7callyac7ve.

2.Theyareopenchainorcyclicunsaturatedcompoundshavingoneormoredoublebonds.Consequently

theyundergoaddi7on reac7onwithhydrogen,halogen, acids, etc.Anumberof addi7onproducts have

an7sep7cproper7es.

3.Theyundergopolymeriza7onanddehydrogena7on

4. They are easily oxidized nearly by all the oxidizing agents. On thermal decomposi7on, most of the

terpenoidsyieldsisopreneasoneoftheproduct.

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Myrcene•  Chemicalformula:C10H16,b.p.166-168°C•  Myrceneisanacyclicmonoterpenehydrocarbonoccurring

inVerbenaoil.isacolorless,liquidwithapleasantodor.

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UV:λmax225nm

Geraniol

•  Chemicalformula:C10H18,b.p.229-230°C. 𝜂20D1.477720D1.4777

•  Geranioloccursincitronella,rose,lemongrassandlavenderoils.Itispresentineitherfreestateorasesters.Itsvariousesterssuchasacetate,formate,butyrateandisovalerateareextensivelyusedinperfumery.IR:υmax ,3400(OH),1695,1105,1090,1000,830cm-1.1HNMR:δ1.62,1.68(6H,C-7methyls),4.15(2H,α allylicCH2OH),5.12(1H,m,H-6),5.45(t,1H,H-2).13CNMR:δ58.7(C-1),124.5(C-2),137.2(C-3),39.7(C-4),26.6(C-5).124.9(C-6),131.2(C-7),25.5(C-8),17.4(C-9),16.0(C-10)..

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Methylisovalerate

Citral•  Chemicalformula:C10H16,b.p.77°C. 𝜂20

D1.489820D1.4898

•  Citralisoneofthemajorcons0tuentsoflemongrassoil.

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Mixtureofatleast4geometricalisomersofdi-olefinicaldehyde

cis-citralTrans-citral

(-)-Menthol

•  Chemicalformula:C10H20O,m.p.34°C,b.p.213°C,[α]D-50°,𝜂20D1.4661.20D1.4661.

•  Mentholisthemajorcons0tuentofMenthapiperitaandhasbeenknowninIndia,ChinaandJapansinceancient0mes.Itismainlyusedasflavouringagentandhasacoolingeffect.Medicinallyitexhibitsan0sep0candanaesthe0cproper0es.Itistheingredientincoldbalms.

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LimoneneOccurrence:•  Limoneneisoneofthemostwidelydistributedterpene,occurringinmanyvola7le

oilsespeciallyincitrusoils.•  Thed-form(+)ispresentorange(90%),lime,grapefruit,biaerorange,mandarin,

neroli,dillfennel.•  The1form(-)islesscommon,accurinpeppermint,spearmint.Therecemicformdl

(±)isknownasdipen7neandoccursinvola7leoilsoflemongrass,nutmeg,neroli,fenneletc.

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Isola7on:

o  Limoneneisisolatedfromthevola7leoileitherbycarefulfrac7onaldis7lla7on,b.p176°Cwithout

decomposi7on,orviacertainderiva7ve(adducts)e.g.,tetrabromidem.p104°-105°C.andthe

hydrocarbonmayberegeneratedbydebromina7onwithzincandace7cacid.

1

89 10

7

Limonene

•  Limoneneisiden0fiedbytheprepara0onofacrystallinenitrosochloridem.p103°-104°C.,bythereac0onwithnitrosylchloridegasandthecrystallinetetrabromide,m.p104°-105°C.

•  Autoxida7onoflimonenetocorveolandcarvoneundertheinfluenceofairandmoisture,ismostprobablyoneoftheprincipalfactorsinthespoilageofpoorlystoredoilsthatcontainhighpercentageoflimonene

e.g.citrusoils.Thisispar0cularlyno0ceableinoldorangeoilsbyshowingpeculiarcarawayodor.

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1

89 10

7

H2O

O2

Uses :•  Limonene is widely employed for scenting cosmetics, soaps as well as for flavoring pharmaceuticals.

Pinene

β- Pinene is a colorless liquid that boils at1630C

Bicyclicmonoterpenoids

α-Pinene, b.p. 156°C. This is the most important member of the pinane class. It occurs in both the (+)- a n d ( - ) - f o r m s i n a l l t u r p e n t i n e o i l s .

Polyterpenoids•  Polymericisoprenoidhydrocarbons;Rubberisoccursasacolloidalsuspensioncalledlatexinanumberof

plantsmainlyinarubbertree(Heveabrasiliensis).

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Rubber:

•  Rubber is obtained from latex, which is an emulsion ofrubber par0cles inwater that is obtained from the innerbarkofmanytypesoftreeswhichgrowinthetropicsandsub-tropics.

•  When the bark of the rubber trees is cut, latex slowlyexudesfromthecut.

•  Addi0onoftheace0cacidcoagulatestherubber,whichisthen separated from the liquor and either pressed intoblocksorrolledintosheets,andfinallydriedinacurrentofwarmair,orsmoked.

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Polyterpenoids

After coagulation, the cake of raw rubber must be rolled to remove the water and washed to remove the acid