(–)-Khafrefungin (TKGP-100626) S.

Kobayashi1), 2)

OH O
O
OH
OH O O OH
HO

Activity Antifungal（抗真菌活性）

(A) vinylogous Mukaiyama aldol reaction, (B) syn-selective aldol reaction,

Key Reactions
(C) anti-dehydration, (D) Mitsunobu reaction

i-Pr

i-Pr i-Pr
Li N O
Et3N
? O NaHMDS;
OH ? N O N O
TBSCl
O O O TBSO O
1

###

i-Pr 1) NaBH4, H2O

ent-1, TiCl4 2) TBSCl, imidazole
H N O OTBS
CH2Cl2 3) ?
O –78 to –40 °C OH O O O
2
(A) C-67

###

1) ?
O H2SO4 O PdCl2, O2 O
HO OH PMBO OAllyl PMBO OH
2) PMBCl, NaH CHCl3-H2O
HO OH PMBO OPMB PMBO OPMB
A-77 C-25

OPMB TBSCl OPMB

NaBH4 HO Et3N HO
OH OTBS
? OPMB OPMB
PMBO PMBO
3
 1) CH3(CH2)8MgBr
1) ? Ni(acac)2
? 1,3-butadiene
MeO OH TsO OBn H
CH3(CH2)9
2) ? 2) ?
O 3) ?, pyridine B-67 O
3) Swern oxidn

i-Pr
1) TBSOTf 2, TiCl4
1, TiCl4 ? i-Pr2NEt
N O H
CH3(CH2)9 CH3(CH2)9
CH2Cl2 2) DIBAL CH2Cl2
–78 to –30 °C OH O O OTBS O –78 °C
C-27
(A) (B)
DIAD
Bu3P
OTBS OTBS
CH3(CH2)9 CH3(CH2)9
THF
OTBS OH O C-19 OTBS O
(C)

1) AcOH
THF-H2O
OH
2) MnO2
3) NaClO2 OTBS O O
NaH2PO4
Me2C=CHMe

3, ? PMBO
?
O
toluene OTBS
OTBS O O OPMB
(D) PMBO

1) ? PMBO O
THF-H2O
O
OH
2) Dess-Martin
oxidn OTBS O O OPMB
3) NaClO2 PMBO
NaH2PO4
Me2C=CHMe

OH O
?
O
OH
CH2Cl2, rt
OH O O OH
HO
(–)-Khafrefungin

References:
1) S.-i. Shirokawa, M. Shinoyama, I. Ooi, S. Hosokawa, A. Nakazaki, S. Kobayashi, Org. Lett., 9, 849 (2007)
2) S.-i. Shirokawa, M. Kamiyama, T. Nakamura, M. Okada, A. Nakazaki, S. Hosokawa, S. Kobayashi, J. Am. Chem.
Soc., 126, 13604 (2004)