The Role of Total Synthesis in Structure …
39
Table 3 Summary of total syntheses of seimatopolide B
Entry
Target
structure
Source of chirality
(stereocenter)
Specific
rotation/°cm 2 (10
g) −1
Conclusion for
structure
assignment
Ref.
1
115
Three Co-salen
catalyzed hydrolytic
epoxide cleavage
reactions (C-3, C-6,
C-9)
−212.6, CH 3 OH
Fully confirmed [141]
2
115
Two Co-salen
catalyzed hydrolytic
epoxide cleavage
reactions (C-3, C-6);
l-proline-catalyzed
amino-oxylation (C-9)
+16.6, CH 3 OH
Absolute
configuration
revised to
(3S,6R,9R)
[142]
3
ent-115
Two Co-salen
catalyzed hydrolytic
epoxide cleavage
reactions (C-3, C-6);
d-proline-catalyzed
amino-oxylation (C-9)
−13.4, CH 3 OH
4
ent-115
Asymmetric
allylboration (C-9);
oxazoborolidine cat.
ketone reduction
(C-6);
lipase-Ru-catalyzed
dynamic resolution
(C-3)
−13.4, CH 3 OH
Revised
(3S,6R,9R)
configuration
confirmed
[132]
same sequence of steps from (R,R)-111 (accessible from d-mannitol, cf. Scheme 22)
and (R)-118 (Scheme 24) [129].
Two further syntheses of levorotatory seimatopolide A (ent-114) (Table 2, entries
6 and 8) [130, 132] and one synthesis of dextrorotatory ent-seimatopolide A (114)
(Table 2, entry 7) [131] corroborated the revision of the absolute configuration of
seimatopolide A from (3R,6R,7R,9S) as originally proposed by Hiep et al. [125] to
(3S,6S,7S,9R). Parallel to the disclosure of the first total syntheses of seimatopolide
A, a correction of the original isolation paper was published that corrected the absolute configuration of seimatopolide A to (3S,6S,7S,9R) and its specific rotation to
–20.8°cm
2 (10 g)
−1 . The absolute configuration of seimatopolide B was revised to
(3S,6R,9R) and the specific rotation to –12.6°cm
2 (10 g)
−1 [140].
Seimatopolide B (115) has attracted less attention from the synthetic community but was still the target of three total syntheses (Table 3). The first synthesis
confirmed the originally assigned (3R,6S,9S)-configuration of naturally occurring
(–)-seimatopolide (Table 3, entry 1) [141]. However, the second total synthesis led to
the conclusion that (3R,6S,9S)-configured 115 is actually the non-natural enantiomer,
(+)-seimatopolide B. Therefore, the structure of seimatopolide B was corrected to
39
Table 3 Summary of total syntheses of seimatopolide B
Entry
Target
structure
Source of chirality
(stereocenter)
Specific
rotation/°cm 2 (10
g) −1
Conclusion for
structure
assignment
Ref.
1
115
Three Co-salen
catalyzed hydrolytic
epoxide cleavage
reactions (C-3, C-6,
C-9)
−212.6, CH 3 OH
Fully confirmed [141]
2
115
Two Co-salen
catalyzed hydrolytic
epoxide cleavage
reactions (C-3, C-6);
l-proline-catalyzed
amino-oxylation (C-9)
+16.6, CH 3 OH
Absolute
configuration
revised to
(3S,6R,9R)
[142]
3
ent-115
Two Co-salen
catalyzed hydrolytic
epoxide cleavage
reactions (C-3, C-6);
d-proline-catalyzed
amino-oxylation (C-9)
−13.4, CH 3 OH
4
ent-115
Asymmetric
allylboration (C-9);
oxazoborolidine cat.
ketone reduction
(C-6);
lipase-Ru-catalyzed
dynamic resolution
(C-3)
−13.4, CH 3 OH
Revised
(3S,6R,9R)
configuration
confirmed
[132]
same sequence of steps from (R,R)-111 (accessible from d-mannitol, cf. Scheme 22)
and (R)-118 (Scheme 24) [129].
Two further syntheses of levorotatory seimatopolide A (ent-114) (Table 2, entries
6 and 8) [130, 132] and one synthesis of dextrorotatory ent-seimatopolide A (114)
(Table 2, entry 7) [131] corroborated the revision of the absolute configuration of
seimatopolide A from (3R,6R,7R,9S) as originally proposed by Hiep et al. [125] to
(3S,6S,7S,9R). Parallel to the disclosure of the first total syntheses of seimatopolide
A, a correction of the original isolation paper was published that corrected the absolute configuration of seimatopolide A to (3S,6S,7S,9R) and its specific rotation to
–20.8°cm
2 (10 g)
−1 . The absolute configuration of seimatopolide B was revised to
(3S,6R,9R) and the specific rotation to –12.6°cm
2 (10 g)
−1 [140].
Seimatopolide B (115) has attracted less attention from the synthetic community but was still the target of three total syntheses (Table 3). The first synthesis
confirmed the originally assigned (3R,6S,9S)-configuration of naturally occurring
(–)-seimatopolide (Table 3, entry 1) [141]. However, the second total synthesis led to
the conclusion that (3R,6S,9S)-configured 115 is actually the non-natural enantiomer,
(+)-seimatopolide B. Therefore, the structure of seimatopolide B was corrected to