Synthesis of Fredericamycin A

Structure of Fredericamycin A

C30H21NO9

Principal investigatorDale L. Boger
Publication year1995
Synthesis typeTotal
Number of steps 27 (3 parts)
References
Part 1 of 3
intermediate structure
MeOCH2Cl, NaH, n-Bu4N+ I-
DMF
0 °C to RT, 24 h, 91%
intermediate structure
mCPBA
CH2Cl2
RT, 16 h
intermediate structure
KOH
MeOH, H2O
RT, 12 h, 85% (2 steps)
intermediate structure
MeOCH2Cl, NaH, n-Bu4N+ I-
DMF
RT, 72 h, 71%
intermediate structure
n-BuLi, Cr(CO)6
Et2O
-78 °C to RT, 2.5 h
intermediate structure
Me3O+BF4-
CH2Cl2
0 °C to RT, 90 min, 78% (2 steps)
intermediate structure
Part 2 of 3
intermediate structure
MeSOCl, Et3N
CCl4
0 °C, 10 min
intermediate structure + intermediate structure
CH2Cl2
RT, 20 h, 47% (2 steps)
"95 % yield based on the alkene."
intermediate structure
DBU
THF
70 °C, 40 h, 81-91%
intermediate structure + intermediate structure
i-Pr2NLi
THF
-78 °C to RT, 3 h, 64-85%
intermediate structure
DDQ
CH2Cl2
RT, 10 min, 87%
intermediate structure
BnBr, K2CO3, n-Bu4N+ I-
DMF
RT, 6 h, 93%
intermediate structure
TosMIC, KOt-Bu
CH2Cl2, EtOH
0 °C to 10 °C, 5 h, 73%
intermediate structure
i-Bu2AlH
THF
-78 °C, 3 h, 97%
intermediate structure
(COCl)2, DMSO, Et3N
CH2Cl2
-70 °C to RT, 40 min, 99%
See the Swern Oxidation
intermediate structure + intermediate structure
n-BuLi
THF
-78 °C to RT, ON, 89%
See the Wittig Reaction
"Ratio of the cis-cis, cis-trans, trans-cis and trans-trans isomers, respectively."
intermediate structure
I2
CHCl3
RT, 4-5 d
intermediate structure
i-Bu2AlH
PhMe
-30 °C, 60 min, 69% (2 steps)
intermediate structure + intermediate structure
n-BuLi
THF
-78 to 0 °C, 2.5 h
"Mixture of diastereoisomers."
intermediate structure
TBSCl, Imidazole
DMF
RT, 22 h, 54% (2 steps)
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
Ac2O
Heptane
50 °C, 47 h, 35%
intermediate structure
BnBr, K2CO3, n-Bu4N+ I-
DMF
RT, 53 h, 50-57%
intermediate structure
n-Bu4N+ F-
THF
RT to 50 °C, 10.5 h
intermediate structure
(CF3CO)2O, DMSO, DBU
CH2Cl2
-78 °C to RT, 21 h
See the Swern Oxidation
See the Aldol Addition
intermediate structure
(CF3CO)2O, DMSO, Et3N
CH2Cl2
-78 °C to RT, 50 min, 57-68% (3 steps)
See the Swern Oxidation
intermediate structure
  1. BBr3
  2. O2
  3. HCl
  4. H2O
CH2Cl2
-78 °C to RT, 4 h
"Partial deprotection of the imide."
intermediate structure
TsOH, NaBr
MeOH
70 °C, 12 h, 85% (2 steps)
intermediate structure