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with polysaccharides and proteins and through various chemical
reactions such as oxidation, hydrolysis, polymerization (Puech
et al
.,
1999a, Viriot
et al.
, 1993) and… condensation events (Quideau
et al.
,
2005). Analyses of wines aged for 12 to 18 months in oak barrels have
indicated amounts of vescalagin (
1
) comprised between 0 and 7 mg/L
(Saucier
et al.
, 2006, Quideau
et al.
, 2005, Moutounet et al., 1989, 1992)
(see also Table 9.1). So, vescalagin (
1
), the
C
-glycosidic ellagitannin part
of the acutissimins, gets extracted from the oak into the wine solution,
which does contain significant amounts of the other part of the hybrid
structure of these complex tannins,
i.e.
, the grape-derived flavan-3-ol,
(+)-catechin. Hence, we surmised that the formation of acutissimins
could occur during wine aging in oak barrels (Section 9.3).
First, we achieved the hemisynthesis of acutissimins A/B (
14
/
15
) in
high yield (87%) from
1
and (+)-catechin in an acidic organic medium
(
i.e.
, 1.5% (v/v) TFA/THF) at 60 °C over a period of 7 h (Quideau
et al.
,
2003, 2005) (Fig. 9.10). Interestingly, the ratio of acutissimins A and B
thus obtained (
i.e.
, 75:25) was similar to that observed from the isolation
of these two regioisomers from
Quercus acutissima
(
i.e.
, 81:19, see
Ishimaru
et al.
, 1987). Thus, the predominant formation of acutissimin A
(
14
)
in vitro
as well as
in vivo
may be strictly a consequence of the better
accessibility and higher nucleophilicity of the catechin C-8 center over
those of the C-6 center (Delcour
et al.
, 1983, Okajima, 2001). The
hemisynthesis of the as yet non-isolated epiacutissimins A (
29
) and B
(
30
) was also achieved using vescalagin (
1
) and (-)-epicatechin under the
same reaction conditions. Both epiacutissimins were obtained in a
combined yield of 78% and in a regioisomeric ratio of 67:33 in favor of
the epiacutissimin A (Fig. 9.10). As mentioned above, all of our attempts
to perform the same reactions from castalagin (
2
) were to no avail. The
mechanistic description of these hemisyntheses follows a classical S
N
1-
type nucleophilic substitution pathway, as first suggested by Haslam
(Haslam and Cai, 1994). The protonation of the OH-1 group of
vescalagin (
1
), under the acid-catalyzed conditions used, leads to the
formation of the stable benzylic cation
27
, which is then trapped by the
nucleophilic flavan-3-ol counterpart (Fig. 9.7). Starting from
1
, these
nucleophilic substitutions proceed with full retention of configuration at
C-1, as rationalized in Section 9.2.1.2. These hemisyntheses constitute an
