Biomedical Engineering Reference
In-Depth Information
OMe
OMe
Mn(OAc)
3
·2H
2
O
Yb(OTf)
3
CF
3
CH
2
OH
-5 to 0°C
60%
O
O
H
O
O
O
O
277
278
(dr = 9.2:1)
steps
OMe
O
Yb(OTf)
3
O
H
O
OH
OH
(+)-Triptocallol
279
280
syn
-orientation,
Si
-face cyclization
SCHEME 9.47
Total synthesis of triptocallol
279
by Yang and coworkers.
and a 9.2:1 diastereomeric ratio. Two additional steps including the removal of
the auxiliary finally led to (
). The stereochemical outcome of the
reaction is deciphered by the authors through the proposed transition state
þ
)-triptocallol (
279
280
,in
which the chelation of the
-keto ester moiety with Yb(OTf)
3
places the two carbonyl
groups in a
syn
-orientation. The attack of the radical, generated from the Mn(III)
oxidation onto the proximate double bond, is then restricted by 8-naphthyl moiety
through the more accessible
si
-face.
The naturally occurring terpenoid stypoldione (
b
283
) has interesting biolo-
gical activities including influencing intracellular calcium concentration and
being cytotoxic in rat cerebellar granule neurons [108]. In a formal synthesis of this
natural product, Cuerva and coworkers have developed a titanocene-catalyzed domino
cyclization involving the formationof six stereogenic centers (Scheme9.48) [109,110].
Upon treatment with [Cp
2
TiCl
2
], epoxypolyene
281
was converted to the complex
trans
/
anti
/
trans
fused tricyclic compound
in moderate yield, with stereoselective
formation of six stereogenic centers. A racemic mixture was obtained since
282
281
was racemic; however, several methods should be available to prepare
281
in an
enantiopure form. The following step to convert
282
to the desired natural product
283
has already been reported [111].
Cp
2
TiCl
2
(20 mol%)
Mn, Me
3
SiCl·collidine
31%
O
OAc
OAc
H
H
HO
HO
O
H
H
O
O
281
282
Stypoldione
283
SCHEME 9.48
Synthesis of stypoldione
283
by Cuerva and coworkers.
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