Synthesis of Penitrem D
C37H45NO4
| Principal investigator | Amos B. Smith, III |
|---|---|
| Publication year | 2003 |
| Synthesis type | Total |
| Number of steps | 56 (3 parts) |
| References |
Part 1 of 3
Methyl acrylate
hν
CH2Cl2
0 °C, 8.5 h
"The product depicted is the major component of an uncharacterized mixture of isomers."
Amberlyst 15,
HC(OMe)3
0 °C, 2.5 h
"The product depicted is the major component of an uncharacterized mixture of isomers."
MeMgBr
Et2O, PhH
0 °C to RT, 90 min
See the Grignard Reaction
"The product depicted is the major component of an uncharacterized mixture of isomers."
Pyr.TsOH
Acetone
RT, 2.5 h, 49% (4 steps)
i-Pr2NEt,
MeOCH2Cl
CH2Cl2
0 °C to RT, 74 h
KOH
H2O, MeOH
Reflux, 71% (4 steps)
NH2OH.HCl,
NaOAc
MeOH
Reflux, 3 h, 83%
NaOH
EtOH, H2O
Reflux, ON, 67% (2 steps)
H2,
Pd(OH)2/C
1 atm
EtOH, i-PrOH, MeOH
RT, 48 h, 96%
DMAP,
i-Pr2NEt,
TBSCl
CH2Cl2
0 °C to RT, 3 h, 88%
"The following protection / deprotection sequence was due to a late deviation from the initial plan."
HCl
H2O, MeOH
RT, 3 h, 89%
DMAP,
TIPSCl
Et3N
RT, 25 h, 95%
DMAP,
TMSCl
Et3N, THF
RT, 48 h, 48%
"The yield was 100% brsm."
Part 2 of 3
+
+
- O2 , Rose Bengal
- Ph3P
hν
THF
-78 °C to RT, 24 h, 50%
+
KOt-Bu,
MeI,
Ph2SO
THF
0 °C to RT, 4 h, 59%
Pyr.TsOH
Acetone, H2O
RT, 24 h, 98%
Zn,
NiCl2.6H2O
Ultrasound
2-Methoxyethanol, Buffer (pH = 9)
RT, 27 h, 90%
- O3
- Me2S
CH2Cl2, MeOH
-78 °C to RT, ON, 86%
"R = Bn, Bz (mixture)"
NaH2PO4,
KMnO4
H2O, t-BuOH
RT, 90 min
"R = Bn, Bz (mixture)"
CH2N2
CH2Cl2, Et2O
RT, 92% (2 steps)
"R = Bn, Bz (mixture)"
H2,
Pd(OH)2
1 atm
EtOH, H2O
RT, 24 h, 92%
"R = Bn, Bz (mixture); R = H, Bz (mixture)"
KOt-Bu
MeOH
Reflux, 3 h, 86%
"R = H, Bz (mixture)"
Neopentyl glycol,
Camphorsulfonic acid
Dean-Stark
PhH
Reflux, 6 h, 96%
i-Bu2AlH
CH2Cl2
-78 °C, 20 min, 83%
HCl
MeOH
0 °C to RT, 2 h, 96%
"Both C1-epimers were separated and the following steps were carried in separate vessels."
MgSO4,
Me2NNH2,
AcOH
PhH
RT, 2 h, 94% / 91 %
"Mixture of E and Z hydrazones."
+
i-Pr2NLi
THF
-78 to 65 °C, 5.5 h
DMAP,
BzCl
CH2Cl2
RT, 18 h, 76% / 60 % (2 steps)
AcOH,
NaOAc
PhH
65 °C, 14 h, 53% / 56 %
HClO4
H2O, MeCN
55 °C, 2 h, 90% / 74 %
H2Cr2O7.2Pyr
CH2Cl2
RT, 5 h, 78%
Et3SiH,
TfOH
PhMe
-40 °C to RT, 90 min, 60%
K2CO3
H2O, MeOH
55 °C, 15 h
EDC,
DMAP
CH2Cl2
RT, 60 min, 90% (2 steps)
SiO2,
O2
1 atm
EtOAc
RT, 40 h, 72%
Ph3P
PhH
RT, 60 min, 93%
Li(s-Bu)3BH
THF
-78 °C, 20 min
TESOTf,
2,6-Lutidine
CH2Cl2
RT, 60 min, 72% (2 steps)
Part 3 of 3
+
+
HCl
H2O, THF
RT, 60 min, 89%
Sc(OTf)3
PhH
RT, 60 min, 62%
DMAP,
Ac2O
CH2Cl2, Et3N
RT, 60 min, 80%
n-Bu4N+ F-
THF
RT, 30 min, 84%
o-NO2PhSeCN,
n-Bu3P
THF
RT, 15 min, 81%
K2CO3
MeOH
RT, 4 h, 82%