Ki Bum Hong @ Wipf Group Page 1 of 13 5/30/2011ccc.chem.pitt.edu/wipf/Current...
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Ki Bum Hong @ Wipf Group Page 1 of 13 5/30/2011
Transcript of Ki Bum Hong @ Wipf Group Page 1 of 13 5/30/2011ccc.chem.pitt.edu/wipf/Current...
Ki Bum Hong @ Wipf Group Page 1 of 13 5/30/2011
Isolation, Background
Streptomyces griseus
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First Total Synthesis of Zincophorin Methyl Ester (Danishefsky)
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Cossy’s Total Synthesis of Zincophorin Methyl Ester
O
Me
OMe
O
Me
OH
Me
OH
Me
OH
Me
OH
MeMe
Me
HHMe
Aldol condensation
O
Me
OMe
O
Me
OP
Me
O
MeHH
MeMe
OP
MeMe
Me
O
Org. Lett. 2003, 5, 4037
28 steps
O
Me
OMe
O
Me
OH
HHMe
MeO
Angew. Chem. Int. Ed. 2002, 41, 2144
PO
Me
HOH
Me
HPO O
OBz
O
Me OBz
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Miyashita’s Total Synthesis of Zincophorin
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Leighton’s Methodology Developments
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Leighton’s Methodology Developments
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Silylformylation-Crotylsilylation/Tamao Oxidation-Tautomerization
Me
BnO
Me
MeOH
Me
nBuLi, AlMe3
BF3 OEt3
TBME, -78 C
43%
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Synthesis of the C(11), C(7), and C(6) Stereocenters
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Completion of the C(1)-C(16) Fragments
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Synthesis of the C(17)-C(25) Fragments
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Completion of the Synthesis
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Conclusions
C(1)-C(16) fragment : five of 10 stereocenter was accessed in just four steps
The synthesis of zincophorin methyl ester : a longest linear sequence of 22 steps
from commercially available 4-hexen-1-ol in 4.2% overall yield
no protection group, nonstrategic redox reactions, chiral auxiliaries
C(6)-C(23) fragment : five steps and 46% overall yield
rely on two applications of the Sc(OTf)3-catalyzed crotylation
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