Synthesis of Retigeranic Acid

Structure of Retigeranic Acid

C25H38O2

Principal investigatorLeo A. Paquette
Publication year1987
Synthesis typeTotal
Number of steps 29 (3 parts)
References
Part 1 of 3
intermediate structure + intermediate structure
NaH, KH
PhMe
Reflux, 20 h, 66%
intermediate structure
  1. O3
  2. Me2S
MeOH
-78 °C to RT, , 79%
intermediate structure
NaH
PhMe
Reflux, 18.5 h, 66%
intermediate structure
LiI.3H2O
DMF
Reflux, 18 h, 85%
intermediate structure + intermediate structure
CuBr.Me2S
THF, Me2S
-78 to 0 °C, 24 h
intermediate structure
HCl
Acetone, H2O
RT, 3 d, 72% (2 steps)
See the Aldol Addition
intermediate structure
ClC(S)O(p-MePh)
Pyr
RT, ON, 73%
intermediate structure
180 °C, 60 min, 99%
intermediate structure
NH2NH2.H2O, K2CO3
Diethylene glycol
150 to 200 °C, 7 h, 72%
intermediate structure
Na2CrO4
AcOH, Ac2O
0 °C to RT, 24 h, 64%
intermediate structure
Part 2 of 3
intermediate structure
i-Bu2AlH
100%
intermediate structure
KH, n-Bu3SnCH2I
intermediate structure
n-BuLi
75% (2 steps)
intermediate structure
  1. O3
  2. Me2S
70%
intermediate structure
TBSCl, Imidazole
DMF
85%
intermediate structure
i-Bu2AlH
100%
intermediate structure
POCl3
Pyr
40-45 °C, , 75%
intermediate structure
CrO3, 3,5-Dimethylpyrazole
CH2Cl2
49%
intermediate structure
VinylMgBr, CuBr.Me2S
50%
"Also isolate was the C3-epimer (15 % yield)."
intermediate structure
NH2NH2.H2O, K2CO3
Diethylene glycol
190 °C, , 73%
intermediate structure
Ph3P, DEAD, ZnBr2
THF
RT, , 91%
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
Mg
Et2O
Reflux, , 13%
"Also isolated was the C3-epimer (40 % yield)."
intermediate structure
  1. O3
  2. Me2S
intermediate structure
Piperidine, AcOH
PhMe
Reflux, 48 h, 41%
intermediate structure
H2, PtO2
AcOH, THF
86%
intermediate structure
TMSCN, KCN, 18-Crown-6
intermediate structure
POCl3, DBU
Pyr
Reflux, , 30%
intermediate structure
i-Bu2AlH
intermediate structure
NaClO2, NaH2PO4, 2-Methyl-2-butene
t-BuOH, H2O
56% (2 steps)
intermediate structure