Synthesis of Aplysistatin

C15H21BrO3
Principal investigator | Elias A. Couladouros |
---|---|
Publication year | 2005 |
Synthesis type | Total |
Number of steps | 19 (3 parts) |
References |
Part 1 of 3

i-Bu2AlH
CH2Cl2
-78 °C, 30 min

H2SO4,
CrO3
Acetone
-20 °C, 7 min, 60 % (2 steps)

(CF3CO)2O
t-BuOH
RT, 60 min, 85%

(DHQD)2PHAL,
K2OsO2(OH)4,
K3Fe(CN)6,
MsNH2,
K2CO3
H2O, t-BuOH
0 °C, 15h, 61%
"97% ee"

Ts2O
Pyr
0 °C, 60 min, 86%

DBU
DMF
RT, 15 min, 87%

LiBr,
Pyr.TsOH
NMP
RT, 60 min, 85%

SnCl4
MeNO2
0 °C, 40 min, 60%

i-Bu2AlH
CH2Cl2
-78 °C, 40 min, 97%


Part 2 of 3
+



t-BuOOH,
Ti(Oi-Pr)4,
(+)-DIPT
4A MS
CH2Cl2
-20 °C, 12.5 h, 80%
See the Sharpless Epoxidation
"95% ee"

DMAP,
Imidazole,
TBDPSCl
DMF
0 °C, 30 min, 95%

Part 3 of 3
+


BF3.OEt2
CH2Cl2
0 °C, 30 min

n-Bu4N+ F-
THF
0 °C, 3 h, 50% (2 steps)


- NaIO4
- NaBH4
H2O, MeOH
RT, 80 min, 75%

DDQ
CH2Cl2, H2O
RT, 3 h, 76%

MnO2
CH2Cl2
RT, 2 h, 93%
