Synthesis of Okilactomycin

Structure of Okilactomycin

C24H32O6

Principal investigatorAmos B. Smith, III
Publication year2007
Synthesis typeTotal
Number of steps 37 (3 parts)
References
Part 1 of 3
intermediate structure + intermediate structure
i-Pr2NLi, LiCl
THF
-78 °C to RT, 24 h, 95%
intermediate structure
i-Pr2NLi, BH3.NH3
THF
0 °C to RT, 3 h, 94%
intermediate structure
DMSO, Et3N, Pyr.SO3
CH2Cl2
0 °C, 30 min, 90%
intermediate structure
n-BuLi, Ph3P+CH3 Br-
THF
0 °C, 3 h, 96%
See the Wittig Reaction
intermediate structure
n-Bu4N+ F-
THF
0 °C to RT, 5 h, 97%
intermediate structure
DMSO, Et3N, Pyr.SO3
CH2Cl2
0 °C, 30 min, 93%
intermediate structure + intermediate structure
Et3N, n-Bu2BOTf
CH2Cl2
-78 to 0 °C, 3.5 h, 93%
intermediate structure
H2O2, LiOH
H2O
0 °C to RT, 2 h, 97%
intermediate structure
Part 2 of 3
intermediate structure + intermediate structure
PhMe
90 °C, 24 h, 88%
intermediate structure
LiAlH4
Et2O
-78 °C to RT, 90 min, 97%
intermediate structure
  1. BnBr
  2. TMS2NNa
  3. n-Bu4N+ I-
THF
0 °C to RT, 70 min
intermediate structure
HF
MeCN
RT, 60 min, 90% (2 steps)
intermediate structure
  1. Li(s-Bu)3BH
  2. PhNTf2
THF
-78 °C to RT, 7.5 h, 82%
intermediate structure
n-Bu3SnH, CO, LiCl, Pd(PPh3)4
THF
70 °C, 5 h, 87%
intermediate structure
CH2Cl2
-78 °C, 60 min, 71%
intermediate structure
  1. KH
  2. Me2SO4
  3. 18-Crown-6
THF
0 °C to RT, 22 h, 96%
intermediate structure
mCPBA
MeOH
0 °C, 30 min, 91%
intermediate structure
  1. NaH
  2. n-Bu4N+ I-
  3. 2-Bromomethylnaphthalene
DMF
0 °C to RT, 36 h, 96%
intermediate structure
  1. NBS
  2. Cp2ZrHCl
CH2Cl2
0 °C to RT, 40 min, 98%
intermediate structure
PhSeH, Cs2CO3
MeCN
RT, 60 min, 93%
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
TMSOTf, i-PrOTMS
CH2Cl2
0 °C, 30 min
intermediate structure
Cp2TiMe2
THF
60 °C, 24 h
intermediate structure
Me2AlCl
CH2Cl2
RT, 5 min, 42% (3 steps)
intermediate structure
Pyr
CHCl3
RT to 60 °C, 2.5 h, 94%
intermediate structure
DDQ
CH2Cl2, MeOH
RT, 60 min, 84%
intermediate structure
  1. TMS2NK
  2. ClCO2Me
THF
-78 to 0 °C, 65 min, 99%
intermediate structure
NaOMe
THF
0 °C, 60 min
intermediate structure
K2CO3, MeI
MeCN
70 °C, 2 h, 88% (2 steps)
intermediate structure
Grubbs-Hoveyda catalyst (2nd gen.)
PhH
80 °C, 24 h
intermediate structure
H2, Pd/C
EtOAc
RT, 15 h, 84% (2 steps)
intermediate structure
  1. n-Bu3P
  2. H2O
  3. H2O2
  4. o-NO2PhSeCN
Pyr, THF
0 °C to RT, ON, 90%
intermediate structure
SeO2, t-BuOOH
CH2Cl2
10 °C, 40 min, 54%
"The yield was 62 % brsm."
intermediate structure
SOCl2, Propylene oxide
Et2O
0 °C, 4 h, 74%
intermediate structure
  1. TMS2NNa
  2. PhSeCl
THF
-78 °C, 30 min, 83%
intermediate structure
Et3NO
DMSO
RT, 12 h, 65%
See the Ganem Oxidation
intermediate structure
NaIO4
H2O, THF
RT, 5 h, 90%
intermediate structure
NaH2PO4, NaClO2, 2-Methyl-2-butene
H2O, t-BuOH, THF
RT, 60 min, 80%
intermediate structure