terpenoids - suli pharmasuli-pharma.com/uploads/lectures/terpinoids_pdf.pdf · 2019-12-22 ·...
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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
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Classifica7on• Terpenoidsareclassifiedaccordingtothenumberofisopreneunitsinvolvedintheforma7onofthese
compounds.
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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)
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• TerpenoidBiosynthesis• Whilewecaniden0fyisopreneunitswithinaterpenoidstructureandusethatinitsclassifica0on,thebuildingblockforterpenoidsynthesisinnatureisisopentenyldiphosphate(formerlycalledisopentenylpyrophosphateandabbreviatedIPP).TherearetwomajorroutestothesynthesisofIPP;namely(1)themevalonatepathwayand(2)the1-deoxyxylulosepathway.
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MevalonatePathwayStep1-ClaisenCondensa0onAnearlystepinthebiosynthesisofcholesterolandother‘isoprenoid’compoundsisaClaisencondensa0onbetweentwoacetylCoAmolecules.Anini0altrans-thioesteraseprocesstransferstheacetylgroupofthefirstacetylCoAtoanenzyma0ccysteine(Reac0on1).IntheClaisencondensa0onphaseofthereac0on,thealpha-carbonofasecondacetylCoAisdeprotonated,forminganenolate(Reac0on2).TheenolatecarbonaUackstheelectrophilicthioestercarbon,formingatetrahedralintermediate(Reac0on3)whichquicklycollapsestoexpelthecysteinethiol(Reac0on4)andproduceacetoacetylCoA.
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• tep2-AldolCondensa7on• AcetylCoAthenreactswiththeacetoacetylCoAinanaldol-likeaddi0on.Subsequenthydrolysisproduces(3S)-3-hydroxy-3-methylglutarylCoA(HMG-CoA).
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Step3-Reduc7onoftheThioesterThethioesterisreducedfirsttoanaldehyde,thentoaprimaryalcoholbytwoequivalentsofNADPHproducing(R)-mevalonate.Theenzymecatalyzingthisreac0onisthetargetofthesta0nfamilyofcholesterol-loweringdrugs.
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Genera0ng(R)-Mevalonate
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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.
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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
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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
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Citral• Chemicalformula:C10H16,b.p.77°C. 𝜂20
D1.489820D1.4898
• Citralisoneofthemajorcons0tuentsoflemongrassoil.
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Mixtureofatleast4geometricalisomersofdi-olefinicaldehyde
cis-citralTrans-citral
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(-)-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
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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.
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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 .
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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