Eptachetidi: biosintesi della Griseofulvina

O O O Me
OH O OMe OH O OMe

O O
MeO OH OH MeO OH OH
O O
SEnz Cl+ Cl
Me griseofenone C
griseophenone C griseofenone BB
griseophenone
reazione
Claisen reazione
Aldol
di Claisen aldolica
reaction reaction
OH O OMe OH O OMe
Me OH
O OMe

O
O MeO O O MeO O O
MeO
Cl Cl
Cl

OMe
O OMe
OMe
O OMe
Griseofulvina
O
O O da penicillium griseofulvum
MeO
MeO O antifungino
Cl
deidrogriseofulvina Cl
dehydrogriseofulvin addizione
Stereoselective reduction
oftrans dibond
double idrogeno
 Ottachetidi: ciclizzazione a Endocrocina
O
O O
HO
O O O

SEnz COOH
COOH
O O O
OH O OH
O O O O
pigmento antrachinonico endocrocina
colorante

O O

MeO HO

OH O OH OH O OH

fiscione emodina

O O

GlucO MeO

OH O OH OH O OGluc
 Starter diversi dall’ acetato: cinnamoyl-CoA
OH
OH OH

O SEnz O
3 x malonyl-CoA
3 x malonil-CoA
=
O O
CoAS SEnz

O O O O O
4-idrossicinnamoil-CoA
4-hydroxycinnamoyl-CoA Aldol reaction
Claisen reaction
OH OH

HO HO
OH

Michael nucleophilic addition on

α,β-unsaturated ketone COOH

OH O OH

-CO2
OH OH

HO HO
O

OH O OH

Naringenina Resveratrolo
 Starter diversi dall’ acetato: hexanoyl-CoA
O O OH
O
3 x3malonyl-CoA
x malonil-CoA Aldol reaction COOH
SEnz reazione Aldolica
CoAS O

esanoil-CoA HO
hexanoyl-CoA
O acido pentilresorcilico
Olivetolic acid
-CO2
OH
E OPP OH
OH geranil PP

HO
H HO
cannabigerolo
cannabigerol
OH olivetolo
olivetol

OH
OH
OH

H O
O
OH CANNABINOLO CBN
TETRAIDROCANNABINOLO THC
CANNABIDIOLO CBD
Z
E

=
 Starter diversi dall’acetato : hexanoyl-CoA
O O SEnz OH O OH O
O
O
7x O
malonil-CoA O O
CoAS
HO OH
O O
esanoil-CoA O
acido norsolorinico

OH O OH OH O
3 OH O OH H
2
1
OH O
O
OH HO OH
HO O
O
O
averufina

OH O OH
H
3 O
1 2
OH O
O
O HO O
OH versiconale acetato
O
 Starter diversi dall’acetato : hexanoyl-CoA

OH O OH H acetyl carbons OH O OH H
lost by hydrolysis
O OH
OH O OH
HO O HO O
O O versiconal
versiconal acetate
formation of new
furan ring

OH O OH H O2 OH O OH H
NADPH
O O
HO O H HO O H
O O

versicolorin A versicolorin B
 Starter diversi dall’acetato : hexanoyl-CoA
OH O OH
H

HO O
O
H
versicolorin A
O
HO O H O
HO
CO2H methylation by SAM
O H
MeO
hydroxyl lost sterigmatocistina
sterigmatocystin
decarboxylation and hydroxylation

O
O O
OH
O
O
H
O O
HOOC O O H

O H O
MeO O

O H
MeO

O -CO2 O O
O
-H2O
O Baeyer-Villiger O O
H H

O O

O H O H
MeO MeO
Aflatoxin B1 Aflatoxin G1
 Aflatossine B1,M1, B2, G1, G2

O O O
O
O O
R H
O O
MeO O H H
MeO O

R= H aflatoxin B1
aflatoxin B2
R= OH aflatoxin M1

O O O O

O O O O
H H
O O
MeO O H MeO O H

aflatoxin G1 aflatoxin G2
 Tossicità delle aflatossine

N N NH2
Guanine residue
NH in DNA N N NH2
N O O
O O HO
N NH
O O
H
O O O
H O
MeO O H
O
H
toxin irreversibly
MeO O
bound to DNA

NH2 O NH2 O
H H
N N
HOOC N COOH HOOC N COOH
H H
O O
SH glutathione HO S
H
H O
toxin irreversibly
O
O bound to glutathione
H
H