Biomedical Engineering Reference
In-Depth Information
Me
Me
Me
TBSO
1.
G-I
(0.5 equiv)
Ethylene (1 atm)
CH
2
Cl
2
, 40°C, 21 h
2. TBAF, THF
42%
HO
OMe
TBSO
OMe
OMe
Me
OTBS
OTBS
Me
194
Me
Me
193
195
(dr > 95:5)
i
-Pr
3
Si
TBSO
O
OMe
Me
Me
Me
192
TBSO
G-I
(0.5 equiv)
Ethylene (1 atm)
MeO
OTBS
MeO
OTBS
TBSO
OMe
45°C, 40 h
OTBS
OTBS
PhMe/CH
2
Cl
2
(9/1)
196
197
198
31%
OTBS
(dr > 74:26)
O
Me
2
AlCl, CH
2
Cl
2
−
20°C, 70%
H
OTBS
H
H
H
Me
Me
Me
O
O
H
B
O
H
O
MeO
A
M
e
H
1. TBAF, THF
Me
C
D
E
F
2. PhI(O), MeCN/ H
2
O
O
OHC
O
H
90%
Me
HO
G
O
O
O
O
H
Me
H
Me
H
H
Me
200
199
OMe
(
−
)-Longithorone A
(dr = 1:1.4)
SCHEME 5.43
Atropdiastereoselective enyne metathesis reactions in the total synthesis of
(
)-longithorone A by Shair and coworkers.
197
195
198
, respectively,
setting the stage for the first of the two biomimetic Diels-Alder events. The
intermolecular [4
þ
2]-cycloaddition between
195
and
198
took place smoothly in
the presence of Me
2
AlCl as the promoter, giving Diels-Alder product
199
in 70%
yield as a 1:1.4 mixture of diastereoisomers. Finally, intramolecular Diels-Alder
reaction engaging bis(
para
-quinone)
were subsequently removed and further elaborated to
and
200
furnished (
)-longithorone A with an
impressive 90% yield (over two steps from
), thus providing evidence in support
of the biosynthetic proposal (Scheme 5.43) [76].
199
5.10. CONCLUSION
Undoubtedly, the metathesis reaction has revolutionized the field of organic synthesis
since its discovery. Originating from a serendipitous industrial discovery, growing
understanding of the metathesis reaction has enabled the development of new
catalysts with far-reaching applications across all fields of chemical synthesis,
particularly in the total synthesis of complex bioactive molecules. Indeed, today
there is a “metathesis mindset” in strategizing chemical synthesis, which has
cemented this powerful reaction as an indispensable asset in synthetic chemists'
toolbox. The utility of this transformation stretches far beyond an academic curiosity,
and its industrial practicality has already been demonstrated in the context of bulk
manufacturing. Equally, tolerance of the metathesis reaction in bioconjugation under
biological systems cannot be understated. Now, the community eagerly anticipates
more revolutionary discoveries from the metathesis arena, pushing the frontier of
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