Biomedical Engineering Reference
In-Depth Information
Si
O
385
(5 mol%)
CH
2
Cl
2
, rt, 4 h
Si
O
steps
OH
96%
Ts
TsN
H
H
H
(-)-Halosaline
387
PCy
3
384
386
Cl
Ru
Cl
Ph
PCy
3
385
HO
OH
H
OTBDMS
385
(5 mol%)
CH
2
Cl
2
, 40°C, 4
h
98%
steps
H
OTBDMS
OH
Ts
N
NTs
389
(-)-Swainsonine
390
388
SCHEME 9.67
Synthesis of (
)-halosaline
387
and (
)-swainsonine
390
by Blechert and
coworkers.
is a domino ring-closing/enyne metathesis that has recently been used in the formal
synthesis of (
)-cochleamycin A by Lee and Mukherjee [148].
9.8. OXIDATIVE OR REDUCTIVE DOMINO REACTIONS
9.8.1. Domino Reactions Initiated by Oxidation
The relatively simple lactone (
isolated from the cyanobacteria
Lyngbya majuscula
has shown antifungal activities. A domino reaction-based
synthesis of this marine natural product has recently been achieved by Borhan and
Schomaker [149]. Initially, treatment of enantiopure
þ
)-tanikolide
392
, derived from 1-bromo-4-
pentene, with oxone and a catalytic amount of OsO
4
afforded the benzyl-protected
tanikolide, presumably through a diol intermediate (Scheme 9.68). Liberation of the
hydroxymethyl group by hydrogenolysis upon treatment with Pearlman's catalyst
eventually led to the natural product
391
.
As the key step in their enantioselective total synthesis of the natural product
FR182877 (
392
), Evans and coworkers invented a remarkable oxidation/twofold
transannular Diels-Alder reaction process. FR182877 (
397
), isolated from
Strepto-
myces
sp. No. 9885, has a similar biological mode of action as paclitaxel [150], and
thus it shows a strong anticancer activity through microtubule stabilization in a wide
range of tumor cell lines. The synthetic sequencewas initiated by the introduction of a
397
O
1.
n-
Bu
4
NHSO
5
/OsO
4
THF (73%)
OH
O
OH
2. Pd(OH)
2
/H
2
EtOAc, rt (87%)
OBn
391
(+)-Tanikolide
392
SCHEME 9.68
Borhan and Schomaker's synthesis of (
þ
)-tanikolide (
392
).
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