4월 20일

4월 20일
1
HO
O
O
O
(생합성 과정)
(building block) (화합물군)
(생리활성)
decursin
OH
O
( ) ( )
( )( )
2
HO
OH
O
O
OH
O
silybin
OCH 3
OH
( ) ( )
( )( )
H 3 CO
OCH 3
3
H 3 CO
H 3 CO
CH 3
CH 3
OH
( ) ( )
( )( )
H 3 CO
OCH 3
schizandrin
4
HO
hinokiresinol
OH
( ) ( )
( )
H 3 CO
5
H 3 CO
O
O
( ) ( )
( )( )
kadsurenone
6.
H 3 CO
HO
H 3 CO
O
O
O
CH 2 OH
(생합성 과정) (building block) (화합물군)
( ) ( ) ( )
OCH 3
(생리활성)
7.
lappaol A
CHO
OH
( ) ( ) ( )
8.
cinnamaldehyde
O
O
O
O
O
H 3 CO OCH 3
OCH 3
( ) ( ) ( ) ( )
podophyllotoxone
9. Lignan, neolignan, norlignan의 의미는
10. dicoumarol의 생리활성 및 이 구조를 바탕으로 하여 합성된 의약품은
11. 간질환에 널리 쓰이며, flavolignan을 함유한 생약은

Mevalonate pathway
CO 2
H 2 O
hv
photosynthesis
mono-, oligo-,
polyosides
1. Monoterpenoids
erythrose-4
phosphate
glucose
GLYCOSIDES
2. Iridoids and Secoiridoids
shikimate
flavonoids
anthocyanins
tannins…
phospho-enol
pyruvate
phenols, quinones,
polyacetylenes
macrolides, fatty acids
lipids…
POLYACETATES
3. Sesquiterpenoids
4. Diterpenoids
SHIKIMATES
pyruvate
acetyl CoA
mevalonate
5. Sesterterpenoids
cinnamates,
lignans,
coumarins
quinones
cycle
amino acid
TERPENES
AND
STEROLS
6. Triterpenoids and Steroids
proteins…
ALKALOIDS
essential oils,
sesqui- and diterpenes,
saponins, cardenolides
carotenes…
Mevalonate pathway
HOOC
OH
mevalonic acid
OH
dimethylallyl PP
(DMAPP) (C5)
OPP
OPP
isopentenyl PP
(IPP) (C5)
Hemiterpenes (C5)
IPP
geranyl PP
(GPP) (C10)
OPP
Monoterpenes (C10)
IPP
IPP
OPP
farnesyl PP
(FPP) (C15)
geranylgeranyl PP
OPP
(GGPP) (C20)
Sesquiterpenes (C15)
Diterpenes (C20)
geranylfarnesyl PP
OPP
(GFPP) (C25)
Sesterpenes (C25)
2 x FPP squalene
Triterpenoids (C30)
Steroids (C18-C30)
2 x GGPP phytoene
Tetraterpenes (C40)
carotenoids

Mevalonate pathway
O
HOOC
SCoA
H
SCoA
O
OH
OH
mevalonic acid
(MVA)
Claisen
reaction
EnzSH
acetyl-CoA
O
reduction of aldehyde
to alcohol
NADPH
HOOC
O
SCoA
SEnz
O
Enzyme-bound
acetyl group
OH OH
mevaldic acid
stereospecific aldol reaction;
also involves hydrolysis of
acetyl-enzyme linkage
O
H
HOOC
OH O
+ EnzSH
SCoA
HMG-CoA
HMG-CoA
reductase NADPH
reduction of thioester to
aldehyde via hemiacetal
OH OH
HOOC
SCoA
H
mevaldic acid
hemithioacetal
sequential
phosphorylation ot the
primary alcohol to a
diphosphate
O
H
O
OH
2 x ATP
O
HO P O ADP
OH
OP
ATP
-CO 2
H
4
5
stereospecific allylic
isomerization; equilibrium
favors DMAPP
3
1
2
OPP
H R H S
isomerase
OPP
ATP facilitates the
decarboxylation-eliminatio
n; the anticipated
phosphorylation of the
tertiary alcohol to make a
better leaving group is
apparently not involved
isopentenyl PP
(IPP)
dimethylallyl PP
(DMAPP)
Acetate-malonate pathway (= Polyketide pathway)
1.General reactions in acetogenins
O O
H 3 C C CH 2 C SCoA
B A
acetoacetyl-CoA
A
+
O
H 3 C C SCoA
acetyl-CoA
B
HO CH 2 COOH
C
H 3 C CH 2 C SCoA
O
O O O
H 3 C C CH 2 C CH 2 C SCoA
isoprenoid
cyclization
reduction
aromatics
fatty acids

Each group of terpenes arises from the head-to-tail condensation of a
variable number of isopren unit
electrophile addition
giving tertiary cation
OPP
dimethylallyl PP
(DMAPP)
OPP
H R H S
isopentenyl PP
(IPP)
OPP
H R H S
stereospecific
loss of proton
OPP
OPP
geranyl PP
(GPP)
Origin of terpenes: formation of the precusors of each class
IPP or DMAPP
DMAPP + IPP = GPP
GPP + IPP= FPP
FPP+ IPP= GGPP
GGPP + IPP= GFPP
2 x FPP = Squalene
2x GGPP = cis phytoene
hemiterpene (C 5
)
monoterpene (C 10
)
sesquiterpene (C 15
)
diterpenes (C 20
)
sesterpenes (C 25
)
triterpene (C 30
)
tetraterpene (C 40
) --- carotenoid
1. Monoterpenes
GPP (generanyl pyrophosphate)가 전구체(C10)
주로 식물에서 발견- 동물이나 미생물에서도 발견
식물 정유의 구성성분으로 존재하기 때문에 수증기 증류나 용매 추출에 의해 분리
구조
- acyclic (myrcane or 2,6-dimethyloctane, secoiridane)
- monocyclic (e.g., p-methane, iridane)
- bi- and trichclic (e.g., carane, pinane, bornane, thuyane)
myrcane p-menthane seco-iridane iridane carane
pinene thujane bornane fenchane iso-camphane
artemisane santolinane chrysanthemane lavandulane
main structureal classes of monoterpenoids

camphor: 녹나무 (Cinnamomun camphor)에서 얻어진 것, 국소자극으로 신경통, 염증,타박상
등에대한찰제, 중추자극작용
menthol: 박하 (Mentha arvensis) 또는 양박하(Mentha piperita)의 정유중에 함유, 피부에 냉
감작용, 약한 마취작용, 진통, 제양작용
paeoniflorin: 적작약 (Paeonia lactiflora)에서 얻어낸 monoterpene glycoside의 benzoate,
진통, 진경, 항염증
limonene: lemon의 정유성분, 진정, 중추억제 작용
fenchon: 회향 (Foeniculum vulgare), 딱정벌레류에 대해서 살충작용
1) acyclic monoterpene 2) monocyclic monoterpene 3) bicyclic monoterpene
OH
OH
OH
OH
OH
O
OH
O
citronellol
(rose oil)
geraniol
(geranium oil)
nerol
(rose oil)
limonene
α-terpineol
(-)-menthol
(levomenthol)
thujone
fenchol
fenchone
β-myrcene
(hops)
O
neral (E-citral)
(lemon oil)
O
geranial (Z-citral)
(lemon oil)
thymol
OH
HO
charvacrol
p-cymene
cineol
O
O
camphor
α-pinene
Irregular monoterpene
GPP를 전구체로 하지 않고 2분자의 DMAPP가 축합하여 생성되는 monoterpenes
-pyrethrins: 제충국 (Chrysanthemum cineraiefolium)등의 꽃에 함유
- pyrethrins, cinerin, jasmolin
- 유용한 살충성분
OPP
electrophilic addition
giving tertiary cation
H
OPP
OPP
loss of proton via
cyclopropyl ring
formation
hydrolysis of phosphate ester;
oxidation of alcohol to acid
OPP
COOH
crysanthemic acid
cf. regular monoterpene skeleton
R 1
O
O
R 2
O
pyrenthrin I, R 1 =CH 3 , R 2 =CH=CH 2
pyrenthrin II, R 1 =COOCH 3 , R 2 =CH=CH 2
cinerin I, R 1 =CH 3 , R 2 =CH 3
cinerin II, R 1 =COOCH 3 , R 2 =CH 3
jasmolin I, R 1 =CH 3 , R 3 =CH 2 CH 3
jasmolin II, R 1 =COOCH 3 , R 2 =CH 2 CH 3
HO
COOH
crysanthemic acid
HO
O
pyrethrolone
COOH
H 3 COOC
pyrethric acid
HO
O
O
cinerolone
jasmolone
O
O N
O
teramethrin
O
O
O
O
bioresmethrin
Cl
Cl
O
O
R
O
permethrin, R=H
cypermethrin, R=CN

2. Iridoids and Secoiridoids
iridoid: cyclopentane ring이 있음
GPP로부터 생합성 됨
쌍자엽 식물에 주로 분포됨
6
7
5
8 9
10
11
4
3
O
1
기본핵 iridoid secoiridoid
geraniol
via hydroxylation
and oxidation
OH
H
O
CHO
H
CHO
H
CHO
iridodial
(keto form)
cyclization formulated as initiated by electrophilic
addition utilizing the unsaturated carbonyl, terminated by
addition of hydride; the Schiff base-assisted mechanism
shown below is more realistic
hemiacetal
formation
H
H
O
OH
iridodial
(enol form)
H
OH
=
H
O
iridodial
(hemiacetal form)
H
O
H
OH
harpagoside- 현삼, 소염진통작용
catalpol- 지황, 혈압강하작용
linaroside- 운란,완화( 緩 和 )작용
geniposide- 치자, 완화, 이담, 지혈, 소염, 강장
해독, 해열
villoside: 패장
loganin, gentioside: 수채엽
syringopicroside: 야정향
valtrate, dehydrovaltrate: 길초근, 진정, 불면증
완화
muzenide: 여정실
picroside I, II, III: 호황련
HO
RO
OH
O
H
OGlc
harpagoside, R=t-cinnamoyl
HO
COOCH 3
H
O
H OGlc
loganin
COOCH
H
3
O
HOH H 2 C OR
genipin, R=H
geniposide, R=Glc
HO
Cl
HO
OH
O
H OGlc
linarioside
CH 2 O-Glc RO
H
H
O
O
O
H HOH
H
O 2 C OGlc
catalpol, R=H
villoside
catalposide, R=p-hydroxybenzoyl
OAc
O
O
O
O
O
H
O
AcO
O
O
H
O
O
HO
O O
H
O
H OGlc
OH
HO
HO
H
O
H OGlc
HO
HO
COOCH 3
H
O
H OGlc
valtrate
O
O
dihydrovaltrate
syringopicroside
aucubin
gardenoside

Secoiridoid:
iridoid의 7,8번 탄소사이가 개환된 상태
Gentianaceae, Rubiaceae, Oleaceae, Cornaceae에 많이존재
secologanin: 인동과 식물 등에 존재, 모든 secoiridoid의 중간체
monoterpene indole alkaloid의 생합성에 중요한 전구체임
용담, 겐티아나, 당약- gentiopicroside, swertmarin, sweroside, amorogentin
O
O
O
O
O
O
O
O
O
OGlc
R
O
H
OGlc
OH
O
OH OH
O
O
O
O
OH
O
ORO
O
O
OAc
O
CH 2 OAc
OH
OGlc
gentiopicroside
swertiamarin, R=OH
sweroside, R=H
HO OH
amarogentin
trifloroside R=COCH 3
benzoyltrifloriside R= CO
4월 22일
OAc
(생합성 과정)
(building block) (화합물군)
(생리활성)
O
1.
O
O
valtrate
O
H
O
O
( ) ( )
( )( )
O
O
2.
O
gentiopicroside
( ) ( )
( )( )
OGlc
3.
COOH
crysanthemic acid
( ) ( ) ( )
4.
OH
(-)-menthol
(levomenthol)
( ) ( ) ( )

5.
Origin of terpenes: formation of the precusors of each class
IPP or DMAPP
DMAPP + IPP = GPP
GPP + IPP= FPP
FPP+ IPP= GGPP
GGPP + IPP= GFPP
2 x FPP = Squalene
2x GGPP = cis phytoene
hemiterpene (C 5
)
monoterpene (C 10
)
sesquiterpene (C 15
)
diterpenes (C 20
)
sesterpenes (C 25
)
triterpene (C 30
)
tetraterpene (C 40
) --- carotenoid