Biomedical Engineering Reference
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Ph
Ph
H
OTMS
54
(2 mol%)
PhCO
2
H
(20 mol%)
O
2
N
O
O
+
MeNO
2
H
H
MeOH, rt, 40 h
80%
Cl
Cl
53
55
(ee = 92%)
NaClO
2
, NaH
2
PO
3
2-methyl-2-butene
t-
BuOH, H
2
O
96%
Cl
-
+
H
2
N
O
2
N
O
O
Ref. [20]
OH
OH
Cl
Cl
Baclofen (
57
)
56
SCHEME 6.10
Synthesis of baclofen via organocatalytic Michael reaction.
In the case of a Michael addition involving an aldehyde and a nitroalkene
catalyzed by a secondary amine catalyst, the first step involves the formation of
the enamine moiety, while the second step concerns the nucleophilic attack on the
nitroalkene that acts as a good Michael acceptor. A final hydrolysis then provides
the corresponding Michael adduct
62
that still bears a reactive aldehyde group
(Scheme 6.12).
Oseltamivir phosphate (Tamiflu
) is a neuraminidase inhibitor and probably
one of the most promising therapeutic used in the treatment of both type A and type B
human influenza (Scheme 6.13) [22]. As such, oseltamivir
63
has been the focus of
many research groups around the world [23].
Ph
Ph
N
H
NO
2
OTMS
Me
O
Me
O
ent
-54
(10 mol%)
+
MeNO
2
Me
H
Me
H
MeOH, rt, 120 h
68%
58
59
(ee = 91%)
NaClO
2
, NaH
2
PO
3
2-methyl-2-butene
t-
BuOH, H
2
O
NH
2
NO
2
Me
O
Me
O
H
2
, Pd/C
Me
OH
Me
OH
80% (2 steps)
Pregabalin (
61
)
60
SCHEME 6.11
Synthesis of pregabalin A.
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