Synthesis of Phyllanthocin

Structure of Phyllanthocin

C25H30O7

Principal investigatorDavid R. Williams
Publication year1984
Synthesis typeTotal
Number of steps 30 (3 parts)
References
Part 1 of 3
intermediate structure
Me2CuLi
Et2O
-78 °C
intermediate structure
3,4-Dihydropyran, TsOH
intermediate structure
LiAlH4
Et2O
RT, 18 h
intermediate structure
TsOH
MsOH
RT, , 70% (4 steps)
intermediate structure
TsOH
Acetone
67%
"Also isolated was the 6-membered acetonide (13 % yield)."
intermediate structure
DMAP, TBDPSCl
CH2Cl2
RT, 2 h, 98%
intermediate structure
TsOH, (CH2SH)2
CHCl3
Reflux, 60 min
intermediate structure
Et3N, TsCl
CH2Cl2
36 h
intermediate structure
NaH
THF
0 °C to RT, , 76% (3 steps)
intermediate structure + intermediate structure
n-BuLi
THF
-78 to 0 °C, 6.5 h
intermediate structure
DMAP, i-Pr2NEt, MeO(CH2)2OCH2Cl
CH2Cl2
0 °C, 2 h, 95% (2 steps)
intermediate structure
Part 2 of 3
intermediate structure
mCPBA
CH2Cl2
10 °C to RT, , 89%
"Mixture of isomers."
intermediate structure
n-BuLi, 2,6-Dimethylpiperidine
Et2O
0 °C to 50 °C, 75 min, 90%
"Mixture of isomers."
intermediate structure
Imidazole, TBSCl
DMF
RT, 9 h, 34%
"Also isolated was the C5-epimer (45 % yield)."
intermediate structure
BH3.THF, H2O2
THF
0 °C to RT, 2 h, 46%
"Also isolated was the C2-epimer (19 % yield)."
intermediate structure + intermediate structure
<50%
"The experimental procedure for this resolution was unavailable in the article."
intermediate structure
KOH
H2O, MeOH
"The experimental procedure for this resolution was unavailable in the article."
intermediate structure
HCrO3Cl.Pyr
CH2Cl2
RT, , 90%
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
t-BuLi, HMPA
THF
-78 to -20 °C, 2 h, 81%
intermediate structure
n-Bu4N+ F-
THF
RT, 2 h, 51-61%
"The epimers were carried on separately."
intermediate structure
HgCl, HgO
H2O, MeCN
RT, 30 min, 42%
"The epimers were carried on separately. Also isolated were 2 isomeric spiroketals (38 % yield, see next step)."
intermediate structure
CF3CO2H
CH2Cl2
0 °C, 1 min, 83%
"Also isolated was the desired CX-epimer (13% yield, see next step)."
intermediate structure
CF3CO2H, MeMgCl
CH2Cl2
RT, 6 h, 63%
intermediate structure
CrO3, H2SO4
Acetone
RT, 45 min, 75%
See the Jones Oxidation
intermediate structure
H2, Pd/C
EtOAc
RT, 45 min, 82%
intermediate structure
CrO3, H2SO4
Acetone
RT, 30 min, 95%
See the Jones Oxidation
intermediate structure
CH2N2
Et2O
RT, 1 min, 100%
intermediate structure
ZnBr2
CH2Cl2
RT, 2 h, 100%
intermediate structure
NaH, Me3S+ I-
DMSO
RT, 30 min, 92%
intermediate structure + intermediate structure
DMAP
CH2Cl2
RT to 40 °C, 8 h, 73%
intermediate structure