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S. Hirose et al. / Tetrahedron Letters 54 (2013) 7040–7043
presence of a carbonyl group (1767 cmꢀ1) in compound 6; 13C NMR
exhibited the presence of an ester moiety (dC 164.3 ppm) (Table 1).
To establish its identity, intermediate II was subsequently treated
with NaBH4, generating compound 7. The 1H NMR spectrum of 7
indicated the presence of two isomeric mixtures at a ratio of 1:2.
The 13C NMR spectrum lacked an ester signal; instead, the appear-
ance of a new signal at 94.9 ppm indicated the presence of an ace-
tal moiety, suggesting a transformation of the ester moiety to an
acetal under reductive conditions. Furthermore, the appearance
of one additional proton signal was observed in 1H NMR, and the
MALDI-TOF-MS showed a peak at m/z 937 [M+Na]+; namely, com-
pound 7 was generated by the one-step reduction of the ester moi-
ety in intermediate II. On the basis of these results and 2D NMR
spectral analysis, the chemical structure of 7 was determined as
shown in Figure 3. Therefore, intermediate II was identified based
on the above results as 6 (Fig. 3), and the relative stereochemistry
of 6 was determined by ROESY correlations (Fig. 4). We have
O
O
OH
3'''
OG
2'''
OH
O
O
O
4'''
O
5'''
6'''
H
1'''
H
H
4'
OH
OH
H
1'
5'
OH
6'
OH
OG
H
HMBC :
ROESY :
Figure 4. Key HMBC and ROESY correlations of 6.
H
OH
OH
6
pro-oolongtheanin-30-O-gallate. Further confirmation
B
named
H
O
O
O
H
that 6 was the reaction intermediate was established by conver-
sion of 6 to 2b in water.
The chemoselectivity of NaBH4-mediated carbonyl reductions
toward aldehydes and ketones is well known; the reduction of es-
ters and lactones by NaBH4, however, requires a large excess of the
reagent, and/or high reaction temperature conditions.14a,b Com-
O
Figure 5. Formation of complex between a-hydroxy and lactone carbonyl group.
pound 6 has a hydroxyl group at the
fore, it was suggested that NaBH4 might form a complex between
the -hydroxy group and lactone carbonyl, thus facilitating nucle-
a-position of lactone. There-
a
of the
a,b-unsaturated ketone and/or transformation to the alcohol
ophilic attack by hydride on the lactone carbonyl group to generate
by lactone ring-opening.
a lactol. Although the hydroxyl group of 6 is also situated in an
When 6 was reacted with methanol instead of water, compound
8 was observed. Electrospray ionization mass spectrometry (ESI-
MS) of 6 showed a molecular ion peak at m/z 943 [MꢀH]ꢀ. More-
over, 1H and 13C NMR data revealed the presence of a methyl ester
moiety; thus the addition of a methoxy unit was suggested
(Table 1). As a result, the chemical structure of 8 was determined
as shown in Figure 3. Compound 8 was formed via recyclization
a-position to the adjacent ketone, the nearly coplanar orientation
of the hydroxyl group with the lactone carbonyl results in prefer-
ential complex formation with the lactone instead of the ketone
(Fig. 5).15a,b When 6 was reduced with an excess of NaBH4 or a
more reactive reducing agent such as LiAlH4, a complex mixture
of products was generated, which was attributed to the reduction
OH
OH
OG
O
4''
O
O
3'''
4''a
OG
2'''
3''
2''
6''
OH
O
4'''
O
HO
O
5'''
OH
HO
OG
HO
8''a
8
8''
6
6'''
CuCl2
1'''
OH
H
1d
2b
O
H
4'
30% Dioxane/H2O
Dioxane (dry)
60oC
OH
H2O
HO
O
4
2
3
8a
4a
1'
OH
5'
OH
HO
O
6'
3 steps yield:30.4%
OG
OH
OH
OH
5
6
NaBH4
MeOH
OH
OH
O
GO
3'''
OG
G = galloyl
O
O
OH
OH
O
2'''
1'''
O
OH
4'''
HO
HO
O
O
5'''
H
O
6'''
H
OH
4'
HO
O
OH
HO
O
1'
6'
OG
5'
OH
OH
OG
OH
OH
8
7
Figure 3. Preparation of 5–8 and 2b from 1d.