A. Nishida, K. Ono1)-3)
(–)-Nakadomarin A (TKGP-101204)
H
O
N
N
CDK4 inhibitor（CDK4 阻害剤）, Cytotoxic（細胞毒性）
Activity
Key Reactions
(A) Diels-Alder reaction, (B) fused furan synthesis from endoperoxide,
(C) RCM in the presence of protected alkyne
1) ?
PhSO2Cl
HN
BsN
O
2) LHMDS
?
O
H
OH
1) ?
Et3N
NBoc
2) ?
BsN
O
O
1) conc HCl;
BsCl
aq NaHCO3
NBoc
E/Z = 78/22
O
neat, 180 °C;
O
2) ?, PPTS
NBs
H
OH
aq H2SO4
BsN
O
dr = 2:1
O
O
1) O3; Me2S
NBs
OTBDPS
O
NBs
OTBDPS TMS
CH2Cl2
MeOH
0 °C
NBs
O
OTBDPS
H
O2, hν
?
HN
THF
–78 to 0 °C
DME
–65 °C
H
TMS
HN
O
NBs
O
HN
OTBDPS
CHO
Ph3P
H
?
anthracene
BsN
CH2Cl2
rt
NBs
MeOH-CH2Cl2
–78 °C
NBs
H
OH
H
2) TFA
?
BsN
benzene
rt
NBs
TBDPSCl
?
?
NaBH4
?
dr = 3:2 O
(A)
H
O
O
NBoc
O
BsN
TFA
CH2Cl2, rt
O
O
toluene
EtOAc, rt
H
?
BsN
BsN
H2, Pd/C
O
O
HN
O
B-34, 35
NBs
OTBDPS
TMS
H
H
Dess-Martin
oxidn
O
t-BuOK, THF;
HN
aq HCl, rt
NBs
O
(B)
TMS
TMS
NBs
O
2) BF3·OEt2
3) K2CO3, MeOH
A-74, C-16
O
OH
H
H
1) ?, ?
2) DIBAL
O
HN
1) ?
naphthalene
O
BocN
3) ?
BF3·OEt2
NBs
O
HN
CH2Cl2
0 °C to rt
H
1) ?
dr = 2:1
O
2) 5-hexenoyl
chloride
Et3N
NBs
H
N
CH2Cl2
rt
O
N
H
O
(CO)3Co
BocN
?
O
BocN
Co(CO)3
O
Grubbs II
O
(CO)3Co
BocN
O
N
CH2Cl2
(1 mM)
reflux
Co(CO)3 1) ?
2) TFA
3) 5-hexenoyl
chloride
Et3N
(C)
H
H
O
O
N
N
O
Grubbs I
H
O
O
CH2Cl2
(0.5 mM)
reflux
?
N
N
O
toluene
reflux
Z/E = 26/46
References:
1)
K. Ono, T. Nagata, A. Nishida, Synlett, 1207 (2003)
2)
K. Ono, M. Nakagawa, A. Nishida, Angew. Chem., Int. Ed., 43, 2020 (2004)
3)
中川昌子, 長田敏明, 小野宏司, 西田篤司, 有機合成化学協会誌, 63, 200 (2005)
O
N
N
(–)-Nakadomarin A