104
H. Zhu et al.
N
H
OH
F10
O
N
H
F11
O
B23, KHMDS,
60% (two steps)
N
H
F12
O
OTBS
TBSO
O
BocN
F13
OTBS
TBSO
OH
O
O
O
BocN
F14
O
OTBS
O
O
O
(EtO)2OP O
BocN
F15
O
OTBS
O
O
O
N
H
110 (cytochalasin B)
O
OTBS
O
O
Dess-Martin,
NaHCO3
1) LDA, Boc2O, 80%;
2)KHMDS, trans-(sulfonyl)phenyloxaziridine, 85%
1) diethylphosphonoacetic
acid, DCC, 81%
2) HF•pyridine, 69%
3) Dess-Martin, NaHCO3
NaOCH2CF3,
CF3CH2OH,
65% (two steps)
BocN
O
OTBS
O
O
O
F16
1) Mg(OCH3)2,
CH3OH, 95%
2) TBAF, THF, 96%
MgSO4, 66%
OBn
O
OBn
OTBS
TBSO
I
OTBS
TBSO
OBn
HO
OBn
H
N
N
S
O2
TBS
1) H2, Pd/C, EtOAc, 87%
2) 1-phenyl-1H-tetrazole-5-thiol,
PPh3, DIAD, 90%
3) m -CPBA, NaHCO3, 84%
1) (1S,2S )-1,2-Salen-Co(II),
AcOH, H2O (0.45 eq), 41%
2) TBSOTf, Et3N
1) H2, Pd/C, EtOAc,
79% (twosteps)
2) PPh3, I2, imidazole,
86%
1) Dess-Martin periodinane
2) TsNHNH2, THF,
94% (two steps)
3) TBSOTf, Et3N
tert-BuLi, Et2O,
90% (two steps).
OBn
OTBS
TBSO
F17
F18
F19
F20
F21
S
OTBS
TBSO
O O
N
N
N
N
Ph
F23
F22
A
B
O
O
Scheme 8 Synthesis of cytochalasin B and intermediate F23
the silyl enol ether group of the resulting carbamate, region-selective deprotonation of the ketone was accomplished by use of potassium bis(trimethylsilyl)amide
(KHMDS) followed by addition of 2-[N,N-bis(trifluoromethylsulfonyl)amino]-5chloropyridine to give the corresponding enol triflate. It then reacted with lithium
dimethylcuprate and afforded the trisubstituted alkene F8. The key intermediate F8
was then oxidized followed by the removal of the N-Boc group and oxidation of
the resultant amine to deliver the imine F9. An intramolecular transamination and
deformylation were achieved in one pot with 1,2-diaminoethane in tert-amyl alcohol,
affording the hydroxylactam F10 in 96% yield.
Compound F10 was then oxidized to aldehyde F11 and coupled with Nphenyltetrazole sulfone F22, which was synthesized as shown in Scheme 8B. The
resulting compound F12 was protected with a Boc group followed by lithiation with
KHMDS, which was trapped with trans-2-(phenylsulfonyl)-3-phenyloxyaziridine to
afford the tertiary alcohol F13 in 85% yield. After esterification with diethylphosphonoacetic acid [275], tert-butyldimethylsilyl ether on the primary alcohol on the amide
F13 was selectively deprotected in the presence of HF/pyridine. The primary alcohol
H. Zhu et al.
N
H
OH
F10
O
N
H
F11
O
B23, KHMDS,
60% (two steps)
N
H
F12
O
OTBS
TBSO
O
BocN
F13
OTBS
TBSO
OH
O
O
O
BocN
F14
O
OTBS
O
O
O
(EtO)2OP O
BocN
F15
O
OTBS
O
O
O
N
H
110 (cytochalasin B)
O
OTBS
O
O
Dess-Martin,
NaHCO3
1) LDA, Boc2O, 80%;
2)KHMDS, trans-(sulfonyl)phenyloxaziridine, 85%
1) diethylphosphonoacetic
acid, DCC, 81%
2) HF•pyridine, 69%
3) Dess-Martin, NaHCO3
NaOCH2CF3,
CF3CH2OH,
65% (two steps)
BocN
O
OTBS
O
O
O
F16
1) Mg(OCH3)2,
CH3OH, 95%
2) TBAF, THF, 96%
MgSO4, 66%
OBn
O
OBn
OTBS
TBSO
I
OTBS
TBSO
OBn
HO
OBn
H
N
N
S
O2
TBS
1) H2, Pd/C, EtOAc, 87%
2) 1-phenyl-1H-tetrazole-5-thiol,
PPh3, DIAD, 90%
3) m -CPBA, NaHCO3, 84%
1) (1S,2S )-1,2-Salen-Co(II),
AcOH, H2O (0.45 eq), 41%
2) TBSOTf, Et3N
1) H2, Pd/C, EtOAc,
79% (twosteps)
2) PPh3, I2, imidazole,
86%
1) Dess-Martin periodinane
2) TsNHNH2, THF,
94% (two steps)
3) TBSOTf, Et3N
tert-BuLi, Et2O,
90% (two steps).
OBn
OTBS
TBSO
F17
F18
F19
F20
F21
S
OTBS
TBSO
O O
N
N
N
N
Ph
F23
F22
A
B
O
O
Scheme 8 Synthesis of cytochalasin B and intermediate F23
the silyl enol ether group of the resulting carbamate, region-selective deprotonation of the ketone was accomplished by use of potassium bis(trimethylsilyl)amide
(KHMDS) followed by addition of 2-[N,N-bis(trifluoromethylsulfonyl)amino]-5chloropyridine to give the corresponding enol triflate. It then reacted with lithium
dimethylcuprate and afforded the trisubstituted alkene F8. The key intermediate F8
was then oxidized followed by the removal of the N-Boc group and oxidation of
the resultant amine to deliver the imine F9. An intramolecular transamination and
deformylation were achieved in one pot with 1,2-diaminoethane in tert-amyl alcohol,
affording the hydroxylactam F10 in 96% yield.
Compound F10 was then oxidized to aldehyde F11 and coupled with Nphenyltetrazole sulfone F22, which was synthesized as shown in Scheme 8B. The
resulting compound F12 was protected with a Boc group followed by lithiation with
KHMDS, which was trapped with trans-2-(phenylsulfonyl)-3-phenyloxyaziridine to
afford the tertiary alcohol F13 in 85% yield. After esterification with diethylphosphonoacetic acid [275], tert-butyldimethylsilyl ether on the primary alcohol on the amide
F13 was selectively deprotected in the presence of HF/pyridine. The primary alcohol