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O
O
O
(EtO)
2
P
CO
2
Et
O
78
O
H
H
O
P(OEt)
2
Cs
2
CO
3
, 0°C, 3 h, evaporation
then EtOH, rt, 15 min
t-
BuO
2
C
t-
BuO
2
C
NO
2
NO
2
CO
2
Et
77
79
STol
O
CO
2
Et
O
CO
2
Et
O
CO
2
Et
steps
5
AcHN
t-
BuO
2
C
t-
BuO
2
C
NH
2
(-)-Oseltamivir
82
NO
2
81
NO
2
(5
R
)
-
80
[(5
R
):(5
S
) = 5:1]
SCHEME 9.15
Synthesis of oseltamivir
82
by Hayashi and coworkers.
Nicolaou and coworkers employed an asymmetric rhodium-catalyzed domino
Michael/aldol process in their synthesis of the spirocyclic skeleton
87
of vannusal A
(88)
, a structurally complex marine natural product isolated from the ciliate species
Euplotes vannus
[30]. Thus, the reaction of cyclohexenone
83
, aldehyde
84
, and vinyl
zirconium derivative
in the presence of a catalytic amount of [Rh(cod)(MeCN)
2
]
BF
4
and (
S
)-BINAP led to
85
in 52% yield and 96% ee as a mixture of
two diastereomers (1.4:1), which was further manipulated to give
86
88
via
87
(Scheme 9.16).
In recent years, amaryllidaceae alkaloids have gained high interest again since
compounds of this family as galantamine are under investigation for the treatment of
Alzheimer's disease [31]. Another alkaloid of this type is (
)-lycorine
(94)
, whichwas
O
OTBS
OTBS
O
OH
O
H
H
84
[Rh(cod)(MeCN)
2
]BF
4
(5 mol%)
(
S
)-BINAP (6 mol%), THF, rt, 12 h
52%
+
C
6
H
13
ClCp
2
Zr
83
C
6
H
13
86
85
(ee = 96%, dr = 1.4:1)
steps
OH
OH
OAc
C
5
H
11
OMe
H
O
OH
H
H
MeO
O
OAc
Vannusal A
88
87
SCHEME 9.16
Synthesis of vannusal A
88
by Nicolaou and coworkers.
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