Biomedical Engineering Reference
In-Depth Information
Me
Me
Me
Me
Me
S
S
S
Me
LnRu
O
re
approach
O
S
O
S
S
G-II
(5 mol%)
H
OH
OH
HO
O
O
O
CH
2
Cl
2
(2 mM), reflux, 1 h
O
O
LnRu
H
O
85%
Me
Me
Me
OH
OH
OH
19
20
21
Me
S
Me
O
S
si
approach
HO
H
O
LnRu
O
Me
H
OH
22
Me
O
Me
Me
S
Me
Me
Me
O
1. IBX, DMSO
25°C, 45 min (50%)
O
H
O
H
O
S
CDCl
3
O
O
HO
O
O
O
2. PhI(OTFA)
2
,
CH
3
CN/H
2
O (10:1)
25°C, 10 min (71%)
O
O
O
25°C, 24 h
H
H
Me
Me
Me
67%
OH
OH
OH
23
(
−
)-Abyssomicin C
(
−
)-
atrop
-Abyssomicin C
SCHEME 5.8
Atropselective ring-closing metathesis in the total synthesis of (-)-
atrop
-
abyssomicin C and (-)-abyssomicin C by Nicolaou et al.
carbenoid and the neighboring tetronic lactone, thereby inducing
p
-facial selectivity
during the [2
was further
subjected to oxidation (IBX, 50%yield) and dithiane deprotection (PhI(OTFA)
2
,71%
yield) to yield (-)-
atrop
-abyssomicin C, which was found to exist as an equilibrium
mixture (ca. 1:2) with the naturally occurring (-)-abyssomicin C in unstabilized
CDCl
3
(Scheme 5.8) [18].
Garsubellin A belongs to a large family of polycyclic polyprenylated acylph-
loroglucinols (PPAPs) natural products and was noted for its neurotrophic activity by
inducing choline acetyltransferase, a key enzyme responsible for acetylcholine
synthesis in the nervous system [19]. The promising biological activity of garsubellin
A, in conjunction with its challenging molecular architecture signified by a highly
substituted bicyclo[3,3,1]nonane-1,3,5-trione core structure, has attracted significant
interest from the synthetic community. Shibasaki and coworkers were the first to
accomplish this feat by employing a ring-closing olefin metathesis reaction to forge
bicyclo[3,3,1]nonane scaffold. In this event, the highly functionalized diene
þ
2]-cycloaddition step (
21
versus
22
). Macrocycle
23
24
underwent smooth ring closure in the presence of Hoveyda-Grubbs second gener-
ation catalyst to generate bicyclic system
25
in 92% yield, which served as a key
intermediate
for
the
racemic
synthesis of
the
targeted natural product
(Scheme 5.9) [20].
OH
O
O
O
O
O
O
HO
O
H
O
O
HG-II
(20 mol%)
O
O
O
O
PhMe, reflux, 48 h
O
O
92%
O
O
MOMO
MOMO
24 25
SCHEME 5.9
Ring-closing metathesis in the total synthesis of (
)-garsubellin A by
Shibasaki and coworkers.
(
±
)-Garsubellin A
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