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TERPENES

1

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C C

C C

C

isoprene isoprene

unit

head

tail

TERPENES

The Czech chemist Leopold Ruzicka ( born 1887 sho!ed that

man" compounds #ound in nature !ere #ormed #rom multipleso# $%e carbons arran&ed in the same pattern as an isoprenemolecule (obtained b" p"rol"sis o# natural rubber'

e called these compounds )terpenes*'

natural

rubber

C C

C

C C

.

2

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+,-N-N. -S,PRENE /N-TS

ead0to0Tail

Tail0to0Tail

The terms head0to0tail andtail0to0tail are o#ten used todescribe ho! the isopreneunits are oined'

an e2trabond

lar&er terpenoidunits dimerizetail0to0tail

indi%idualisoprene unitsoin head0to0tail

3'' e2plained later 3

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limonene dia&ram sho!in& ho! t!oisoprene units combine to#orm the limonene skeleton

from lemon and

orange peels

TERPENES C4N 5E S,6N T, 5E,RE9 R, -S,PRENE /N-TS

head totail

4

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Beberapa contoh senyawa terpena

5

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E:4L,N-C 4C-9 P4T64;

TERPENES

6

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4CET;L Co4 /N-TS 4RE L-N

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CH2

C

S

O

CoAC

O

OH

malon"l Co4

Enz05=

C

O

CH3

S CoA

acet"l Co4

0 C,@

CH2

C S

O

CoA

O CH3

C

O

O''

TE ENA;ES T4T 4SSE5LE 4CET;L0Co4 /N-TS /SE 4 9EC4R5,B;L4T-,N , 4L,N;L0Co4

4 )REE* EN,L4TE -,N -S NE:ER ,RE9

CH2

CS

O

CoAC

O

OH

Enz05=''

CH2

CCH

2

O

C

O CH3

S CoA

O

CH3

C

O

CH2

C

O

CH2

C

O

CH2

C

O

CH2

C

O

SCoA

a pol"ketide chain

2@

2

2D 2

21

)ST4RTER*

)C4-N EBTEN9ER*

8

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CH2

CS

O

CoAC

O

OH

C

O

CH3

S CoA

0 C,@

CH2

C

S CoA

C

CH3

O O

''

CH2

CCH

2

O

C

O

CCH

3

O

SCoA

P,L;

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C

CH2

CH2

CH3

OH C

C

O

O

SCoA

SCoA

acet"lCo4 C

CH2

CH2

CH3

OH C

C

O

O

SCoA

SCoA

H

C

CH2

CH2

CH3

OH C

C

O

O

SCoA

H

C

CH2

CH2

CH3

OH C

CH2

O

SCoA

OH

C

CH2

CH2

CH3

OH C

CH2

O

OH

OH

me%alonic acid

E:4L,N-C 4C-9 P4T64;,R4T-,N , E:4L,N-C 4C-9 R, 4CET;L /N-TS

N49P

N49P@,

''= =0

1!

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C

CH2

CH2

CH3

OH C

CH2

O

OH

OH

me%alonic acid

C

CH2

CH2

CH3

O C

CH2

O

O

O

P H

P P

=50Enz

@ 4TP

49P

4P

CH2H

CH2

CH3

OPP

CH3H

CH2

CH3

OPP

F0dimeth"lall"lp"rophosphate

isopenten"lp"rophosphate

Enz05= G

E:4L,N-C 4C-9 P4T64;The isopenten"l and F0dimeth"lall"l p"rophosphate intermediates

These $%e0carbonintermediates areresponsible #or the#ormation o# all theterpenes'

94PP -PP

11

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,6 TE TERPENES 4RE ,RE9

12

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CH2

H

CH2

CH3

OPP

CH3

H

CH2

CH3

OPP

-PP 94PP

CH3

CH2

H

OPPCH2

OPP

CH2

OPP

H

OPP

CD C1H

CH2

OPP

CH2

OPP

C1DC@H

CDisopenten"l0PP

F0dimeth"lall"l0PP

C1H&eran"l0PP

C1D#arnes"l0PP

C@H&eran"l0&eran"l0PP

C,NC4TEN4T-,N , CD (-S,PRENE /N-TS

=5

a&ain

T4-L

E49

E4C NE6 /N-T -S +,-NE9 E490T,0T4-L13

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CL4SS--C4T-,N , TERPENES

T;PE , N/5ER , -S,PRENETERPENE C4R5,N 4T,S /N-TS

hemiterpene

terpenesesIuiterpene

diterpene

triterpenetetraterpene

CD

C1H C1D C@H

CH

CH

one

t!o three

#our

si2 ei&ht

hemi J hal# di J t!osesIui J one and a hal# tri J three

tetra J #our

N,TE=

sesterterpene C@D$%e

14

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S,E TERPENES (C1H

C"2#"

#"

0pinenecamphor

&eraniol mentholrose and other flowers peppermint

camphor tree turpentine

#

15

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(+0car%one J cara!a" seed

(-0car%one J spearmint(+0limonene J oran&es

(-0 limonene J lemons

ost c"clic monoterpenes ha%e a distincti%e odor 0 basis o# per#ume K a%or industries

Stereoisomersha%e di>erent characteristic smells 0 demonstrates that smell receptors are 9 proteinsFi'e' chiral en%ironments that can distin&uish enantiomers

16

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SESM/-TERPENES

CH3

CH3

CH CH3

CH3&uaiazulene

&eranium oil

CH3

CH3

CH3

car"oph"llene

oil o# clo%es17

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cedrenecedar !ood oil

CH3

CH3

CH3 CH3

CH3

CH3

H3C

lon&i#olenepine species

3'' more sesIuiterpenes

18

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Biosynthesis of $es%uiterpenes &C15'

rearran&ed to #ormsesquiterpenes(C15

Geranylp"rophosphate(C10

Farnesylp"rophosphate(C15

Pren"l trans#erase G

94P -PP

0 i# "ou introduce a labeled carbon in the

precursorF "ou can see !here it ends up in the $nal natural product

1

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Biosynthesis of $es%uiterpenes &C15'

rearran&ed to #ormsesquiterpenes(C15

Geranylp"rophosphate(C10

Farnesylp"rophosphate(C15

Pren"l trans#erase G

94P -PP

0 i# "ou introduce a labeled carbon in the

precursorF "ou can see !here it ends up in the $nal natural product

2!

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(abeling studies in Biosynthesis 1

/sin& isotopicallyenrichedprecursorsF it is possible to trace the incorporation o# buildin& blocks into comple2 metabolites

0 #ollo! the label and see !hich atoms in the natural product end up labeled

,ri&inall" done !ith radioactivelabels(14

CF3

0 #eed cells a precursor !ith one 14C

0 use chemical de"radationto break natural product apartFsee !hich pieces contain the radioacti%it"

0 dra!back= slopp"F usuall" not possible to completel"determine bios"nthetic route

21

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(abeling studies in Biosynthesis 2

No! done b" NR usin& non-radioactiveisotope

13

C 0 common carbon isotope 1@C is in%isible to NR

0 rare 13Chas nuclear spin IJ n@F so is detectable b" NR

0 #eed cells a precursor !ith one position 13ClabeledO

then see !hich positions sho! e2a&&erated peaks in the carbon NR spectrum

since onl" 1 o# carbons are naturall" 13CF the positions that incorporate the label !ill &i%e much hi&her peaks

22

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1C NR spectrum o# compound #F a#ter #eedin& sea slu& !ithQ@01C me%alonate 0 increased size o# peaks sho!s label incorporation

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0 allo!ed researchers to in#er bios"nthetic path!a" #or these related C0@ and C0@1 terpenes

24

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C"3

C"3

C"3

C"3

#"

C"3

C"3C"3

ambreinamber&is

TR-TERPENES

T4-L0T,0T4-L

25

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4ll steroids are triterpenesbut their skeletons ha%e beenrearran&ed so that the" cannot be anal"zed into isopreneunits'

C"3

C"3

C"3

C"3

C"3 C"3

"#

rearran&ementsin this area

STER,-9S 4RE TR-TERPENES (CH

26

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0carotene

carrots

TETR4TERPENE

tail0to0tailhead0to0tail

head0to0tail

27

C,NC4TEN4T-,N , CD (-S,PRENE /N-TS

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CH2

H

CH2

CH3

OPP

CH3

H

CH2

CH3

OPP

-PP 94PP

CH3

CH2

H

OPPCH2

OPP

CH2

OPP

H

OPP

CD C1H

CH2

OPP

CH2

OPP

C1DC@H

CDisopenten"l0PP

F0dimeth"lall"l0PP

C1H&eran"l0PP

C1D#arnes"l0PP

C@H&eran"l0&eran"l0PP

C,NC4TEN4T-,N , CD (-S,PRENE /N-TS

=5

a&ain

T4-L

E49

E4C NE6 /N-T -S +,-NE9 E490T,0T4-L 28

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CH 4N9 CH /N-TS 4RE ,RE9 9-ERENTL;

E-TERPENES CD 1 -PP or 94PP

,N,TERPENES C1H@ &eran"l0PP

SESM/-TERPENES C1D #arnes"l0PP

9-TERPENES C@H &eran"l0&eran"l0PP

C@DD uncommon

TR-TERPENES CH @ 2 (#arnes"l0PP

CD7 uncommon

TETR4TERPENES CH8 @ 2 (&eran"l0&eran"l0PP

Class o# Carbons /nits ,ri&in

-sopreneNumber

2@

2@

SESTERTERPENE

2

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9-ER-A4T-,N , C1D 4N9 C@H /N-TS

CH2

CH3

R

OPPC

CH3

O

R

PO O

O

CH2

CH3

R

PO O

O

CH

CH3

O

R

H

CH3

R

PO O

O

CH3

O

R

CH2

CH

CH3

RH

CH3

R

=0

N49 N49G

Enz05=

P OO

O

O

CH2

CH3 R

rearran&e

dimerize

T4-L

T4-L

+,-NE9S;ETR-C4LL;

T4-L0T,0T4-L/N-TS 4RE +,-NE9 T4-L0T,0T4-L 3!

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C,,N TERPEN,-9 S

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TERPEN,-9S

32

H

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OPP

H

O

OH

H

OOH

HH

&eran"l0PP (.PP

OPP

linal"l0PP (LPP

&eraniol&eranium oil

&eranial&eranium oil

citronellol

citronellal

rose oil

citronella oil

OPP

ner"l0PP (NPP

OH

0m"rcenehops

linaloolcoriander oil

H

O

OH

nerallemon oil

nerolrose oil

OH

0terprneol 33

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OPP

G

G

LPP

,PP0

or

G

GG

0pinene

0pinene

G

OHO

#enchol#enchone

1F@0alk"lshi#t

0 G

0 G

@,

N49PG

ionize

OH

O

G

0 G

camphene

borneol

camphor

1F@0alk"lshi#t

@,

N49PG

meth"l

0terpin"l cation

34

T4B,L

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T4B,L

OPP

G

(G

GH

H

G

G

ta2adiene

OOOO

OH

OH

OH O OH

CH3

O

H

OOOO

OH

O

O O OH

CH3

O

H

O

OH

NHO

CH3

O

paclita2el(ta2ol

man" steps=o2idationsF

esteri$cation

Phe

Phe

Phe

acet"lCo4

acet"lCo4

Paci$c ;e! (bark

1HH0"r0old trees J 1 &

/sed clinicall" in treatmento# breastF o%arianF lun&FheadF neck cancers'

..PP

35