Biomedical Engineering Reference
In-Depth Information
2.2.1.7. Reveromycin B The family of reveromycins constitutes a new class of
potent antiproliferative agents against some human cell lines. It is assumed that they
interact with the epidermal growth factor (EGF), which signals cellular prolifer-
ation. These biologically active compounds were extracted from a culture broth of a
strain of
Streptomyces
. Since very small amounts of material were available from
the extraction, a synthesis of reveromycin B
was initiated and eventually
completed by Drouet and Theodorakis [20] thus confirming the structure of the
natural product and providing a synthetic route to various analogues. The key
intermediate of the synthesis, compound
49
50
, was prepared by coupling
51
and
52
together (Scheme 2.16).
The first type of coupling that was considered was a Stille coupling as
compound
via a hydrostannylation
(Scheme 2.17). Interestingly, the only solvent that allowed the exclusive formation
52a
could easily be accessed from alkyne
53
O
HO
2
C
O
Me
Me
H
O
HO
2
C
CO
2
H
O
Me
OH
Me
Me
49
Negishi coupling
O
Me
Me
H
O
O
CO
2
TMSE
O
OTiPS
Me
50
Me
O
Me
Me
H
O
O
Y
X
+
CO
2
TMSE
O
OTiPS
Me
51a
[X = I]
51b
[X = ZnCl]
52a
[Y = Sn(
n
-Bu)
3
]
52b
[Y = I]
Me
SCHEME 2.16
Retrosynthesis of reveromycin B
49
.
O
O
Me
H
H
O
O
Cp
2
ZrHCl, benzene
O
O
I
I
2
, CCl
4
53%
O
O
Me
Me
Me
53
51a
Me
Me
Me
Me
Me
n-
Bu
3
SnH
I
2
CH
2
Cl
2
, rt
90%
Sn
n-
Bu
3
I
CO
2
TMSE
CO
2
TMSE
CO
2
TMSE
PdCl
2
(PPh
3
)
2
(2 mol%)
Benzene
91%
OTiPS
OTiPS
OTiPS
52a
52b
SCHEME 2.17
Synthesis of the coupling partners.
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