tổng hợp nghịch
tổng hợp nghịch
tổng hợp nghịch
Ph C OH
Ph
N
H
N
CO
2
Et
FGI
1) PhMgBr
2) NaOH, BuOH
FGI,
RETRO GRIGNARD
ClCO
2
Et
TEA
RETRO ACILAZIONE
FRIEDEL CRAFT
COOEt
FGI
Retrosynthesis of Minaprine -Antidepressant
N N
Ph
1 2
3
4
5
6
N N
Ph Cl
N N
Ph O
POCl
3
N N
Ph O
NH
2
NH
2
PhCO
Br, AcOH,
O
N
C Ph
CN
AlCl
3
CH
2
Cl
2
Ph
H
2
C C
CH
3
CO
2
R
O
O
O
FGI
RNH
2
,
FGI
FGI
FGI
2
1
1
FGI
2
RETRO ACILAZ.
FRIEDEL - CRAFT
H
H
Ph
O
CO
2
H
O
OR
O
O
HO
N
H
N
O
O
H
H
H
H
OH
H
MeO
H
H
H
OH
H
LiC CH
MeO
H
H
H
O
MeO
H
O
H
MeO
OAc
MeO
O
OH
MeO
O
O
MeO
OH
17
1)
2) NH
4
Cl / H
2
O
O
O
FGI
H
+
,
RETRO
ETINILAZIONE
FGI
RETRO
BIRCH
1) Li / NH
2
(l)
2) Al (O
i
Pr)
3
,
FGA, FGI
1) H
2
,Pd / CaCO
3
2) KOH, MeOH
RETRO
KNOEVENAGEL
FGI
1) Ac
2
O, Py
2) TosOH,
FGI
RID.
ENZ.
a
d
RETRO
TORGOR
KOH, MeOH
a
d
*
*
Retrosynthesis of (+)-Norgestrel
19-Nor Steroid
FGI
O
RO
2
C
O
C
8
H
17
O
Me
Me
FGA
O
RO
2
C
O
O
Me
Me
C
6
H
13
RETRO
WITTIG
O
RO
2
C
O
CHO
O
Me
Me
Retrosynthesis of Avenaciolide
O
RO
2
C
O
O
Me
Me
HO
HO
FGI
FGA
O
O
O
Me
Me
O
O Me
Me
CO
2
R
H
RETRO
WITTIG
O
O
O
Me
Me
O
O Me
Me
O
FGI
O
OH
OH
OH
OH
HO
D-GLUCOSIO
CON
O
O
O
C
8
H
17
H H
H
2
C
O
d
a
RETRO
METILENAZ.
O
O
O
C
8
H
17
H H
O
O
O
O
C
8
H
17
O
FGI
O
O
OH
C
8
H
17
O
O
OH OH HO
(-)-Pentenomicina
FGI
O O
Me Me
AcO
O
FGI
O O
Me Me
BuO
O
d
a
RETRO
ALDOLIC
CHO
Me
O O
Me Me
BuO
O
FGI
O
O O
Me Me
BuO
H
2
C
OMe
O
O O
Me Me
BuO
OMe TsO
O
BuO
TsO
OH O
O
Me
Me
O
BuO
O
OH O
O
Me
Me
O Me
Me
FGI
O
OHC
O
OH O
O
Me
Me
O Me
Me
RETRO
NEF
O
O
OH O
O
Me
Me
Me
Me
O
2
N
d a
RETRO
HENRY
O
O
O
O
Me
Me
O Me
Me
O
D-GLUCOSIO
Retrosynthesis of Pentenomicina
Retrosynthesis of 11-Deoxy-8-aza-PGE
1
N
O
(CH
2
)
6
-CO
2
R
CO
2
R
N
O
(CH
2
)
6
-CO
2
R
C
5
H
11
OH
Zn(BH
4
)
2
RX
NaH
NH
O
CO
2
R
CH
2
N
2
CO
2
H
HO
O
NH
2
H
N
O
(CH
2
)
6
-CO
2
R
CHO
NH
O
CO
2
H
H
N
O
(CH
2
)
6
-CO
2
R
C
5
H
11
O
11-Deoxy-8-aza-PGE
1
FGI
RETRO
WITTIG
FGI
1) K
2
CO
3
2) ClCO
2
Et, TEA
NaBH
4
3) CrO
3
.
2Py
R = Me, H
FGI
FGI
(R)-Acido Glutammico
Baraldi,P.G. et al. J.Org.Chem.,1979,10,1734
CO
2
R
CH
2
CO
2
R
O
CO
2
H HO
2
C
Br
CH
2
CO
2
R
O
CO
2
R RO
2
C
CO
2
R
EtONa
CO
2
R
CO
2
R
RO
2
C
CO
2
R RO
2
C
CO
2
R
RO
2
C CO
2
R
CO
2
R
RO
2
C
1
1
RETRO
DIECKMANN
2
2
RETRO
MICHAEL
a
3
d
3
FGA
FGI
CO
2
R
, DMSO
160C
Retrosynthesis of 4oxocyclopentane-
1,2-dicarboxylic acid
O O
OH
OTos
OH
OH
O O
RO
2
C
O
O
O
O
O
RO
2
C
RO
2
C
O
OHC
OHC
O
O
O
cis-3-Ossabiciclo
3.3.0 -Ottan-7-one
FGA
1
1
RETRO
DIECKMANN
FGI, FGI
1) CrO
3
2) CH
2
N
2
RETRO
OZONOLYSIS
FGI
TEA
FGI
FGI
TosCI
TEA
RETRO
DIELS - ALDER
LiAlH
4
EtONa,
O
3
etrosynthesis of cis-3-oxabicyclo[3.3.0]octan-7-o
Baraldi,P.G. et al.,Tetrahedron,1984,40,761
Retrosynthesis of Diidroiasmone
O
RETRO
ALDOLIC
O
O
OH
-
FGA
Fe(CO)
5
OH
-
/ H
2
O
O
O
1) H
2
, PtO
2
2) PhCOCl, Py
3) NaBH
4
4) H
+
O N
O
O
PhNCO
TEA
NO
2
O O
1-Esino
(CH
2
OH)
2
H
+
NO
2
O
TMG
O
CH
3
NO
2
Baraldi,P.G. et al..J.Org.Chem.,1979,44,105
Retrosynthesis of PGF
2
CO
2
H
HO
HO
HO
O
O
THPO
NO
2
O
THPO
CO
2
R
NO
2
O
THPO
CO
2
R
O
CO
2
R
N
CHO
CO
2
Me
CO
2
R
THPO
THPO
O
N
O
O
O
THPO
C
5
H
11
O
HO
CO
2
R
O
Br
CO
2
R
PGF
2
FGI
RETRO
WITTIG
FGI
1-Eptino
FGI
d a
RETRO
MICHAEL
FGI FGI FGR
2) DHP, pTsOH
4) H
+
1) Wittig
1) Na, NH
3
(l)
2) Si O
2
3) NaBH
4
N
CHO
CO
2
R
O
CO
2
R
Br
NBS
O
CO
2
R
THPO
NO
2
O
O
THPO
CO
2
H
THPO
THPO
N O
PhNCO
CH
3
NO
2
O
CO
2
R
H
2
O
O
O
THPO
N O
C
5
H
11
O
CO
2
R
THPO
NO
2
H
+
O
CO
2
R
HO
O
CO
2
R
THF,
DHP
1)
2) H
+
BuOH,
CCl
4
,
Diossano
pTsOH
TMG, 0C
LiAlH(O
t
But)
3
1-Eptino
PGF
2
O
OH
THPO
N O
C
5
H
11
DIBAH, -78C
1-Eptino
Synthetic scheme of PGE
2
Baraldi,P.G. et al. Tetrahedron,1987,43,4669
FGI
O O O
O
O
FGI
AcOH, 0C
O O O OH
O
O
FGI AcOH,0C
RETRO
CICLOADDIZIONE
3+2 DIPOLARE
PhNCO
TEA
HO
NO
2
TMSO O
NH
2
O
O O
CH
3
NO
2
Mo(CO)
6
O O O
H
O O O
O
N
TMSO
O
1
2
3
4
5
FGI
HO O O
H
OH
TMSO
NO
2
FGI
DEAD
Ph
3
P
Geiparvarin
Retrosynthetic Route to Geiparvarin
Baraldi,P.G. et al. Tet.Lett.1985, 43, 531
O
HC
2
O
FGI
H
+
, RT, 5d
Sarcomicina
O
O
O
FGA, FGI
H
+
, RT, 6 h.
O
O
O
O
CO
2
H
FGI
CrO
3
, H
+
0C
O
O
O
O
CH
2
OH
FGI
1) O
3
, -78
2) NaBH
4
O
O
CO
2
R
FGI
MED
TosOH
CO
2
R
O
RETRO
DIELS-ALDER
, 3 d
O O
Br
CO
2
R
Retrosynthesis of Sarcomycin
Baraldi,P.G. et al. J.Chem.Soc.Chem.Com.1984,1049
Retrosynthesis of Carbaprostacycline
CO
2
H
C
5
H
11
OH
OH
Carbaprostacycline
FGI
RETRO
WITTIG
O
C
5
H
11
OTHP
OTHP
FGI
C
5
H
11
O
OTHP
O O
RETRO
WITTIG
CHO
OTHP
O O
FGI
CO
2
R
O O
O
FGI
CO
2
R
O
O
O
O
CO
2
R
RETRO
MICHAEL
K
2
CO
3
O
O
CO
2
R
RETRO
CLAISEN
1) Im
2
CO
2) CO
2
Et
CH
2
CO
2
H
Mg(OEt)
2
CO
2
H
O
Jones
FGI
CO
2
H
OH
FGI NaOH
NaOH, H
2
O
2
RETRO
BAYER-WILLIGER
O
O
O
Retrosynthesis of a intermediate for
Carbaprostacycline
Baraldi,P.G. et al. J.Org.Chem.,1980,45,4776
Synthesis and Retrosynthesis A
2B
Agonists
N
N
N
N
NH
2
O
OH OH
HO
N
N
N
N
NH
2
O
O O
HO
N
N
N
N
NH
2
O
O O
HO O
N
N
N
N
NH
2
O
O O
H
N O
N
N
N
N
I
O
H
N O
N
N
N
N
HN
O
OH OH
H
N O
O
N
H
O
R
NH
2 O
NH
O
R
O O Isopentylnitrite,
CH
2
I
2
KMnO
4
,
KOH
1) SOCl
2
2) EtNH
2
2) TFA, H
2
O
1)
p-TsOH,
2,2-dimethoxypropane
P. G. Baraldi et al., Bioorg. Med. Chem., 15, 2007, 2514-2527
R = Ph
hA
1
K
i
= 8.5nM
hA
2A
K
i
= >1000nM
hA
2B
EC
50
= 7.3nM
hA
3
K
i
= 38.4nM
Synthesis and Retrosynthesis A
2B
Antagonists
N
N
O
O
N
H
N
N
N
N
H
N
N
N
H
O
Cl
N
N
N
N
H
OEt
O
+
HN
O
Cl
N
N
O
O
NH
2
NH
2
2: NaOH
1:
, EDC
KOH
EtONa,
p-Cl-acetanilide
O
O
OH
O
OEt
Cl
N2-alkylated product
hA
1
K
i
>1000nM
hA
2A
K
i
>1000nM
hA
2B
IC
50
= 7nM
hA
3
K
i
>1000nM
P. G. Baraldi et al., Bioorg. Med. Chem., 16, 2008, 2419-2430
S
NBoc
O
S
OR
NBoc
X
S
OBn
NBoc
TEMPO
S
OBn
I
NBoc
S
R
OBn
X
S
OR
COOEt
S
COOEt
COOH
CHO
S
t-BuOK,
diethyl
succinate
AcONa, Ac
2
O
(2 steps)
K
2
CO
3
BnBr
R = Ac, 3
R = H, 4
R = Bn, 5
DPPA
NIS
R = COOH, X = H, 6
R = NHBoc, X = H, 7
R = NHBoc, X = I, 8
LiOH
NaH, allyl bromide
TEMPO,
(Me
3
Si)
3
SiH
Zn powder
DBU
PPH
3,
CCl
4
Pd/C, H
2
CO
2
NH
4
R = Bn, X = OH, 11
R = Bn, X = Cl, 12
R = H, X = Cl, 13
Chiral column
(2 steps)
1
2
9
10
14
N
O
Baraldi P.G., Boger D.L., et al.
JACS., 2007, 129, 14092-14099
Synthesis and Retrosynthesis of sulphur Duocarmycins