Biomedical Engineering Reference
In-Depth Information
to two different products, 1-(benzo[
d
][1,3]dioxol-5-yl)-3a,5-dihydropyrrolo[1,2-
a
]quinoxalin-4(1
H
)-one
169
and an acyclic product
170
, depending on the cleavage
conditions.
Related work described the Diels-Alder reaction of resin-bound acyl- and arylni-
troso derivatives with dienes and yielded oxazine derivatives that were transformed
further [48]. The synthesis was carried out using different linkers: Rink amide
I
,
diisopropylsilyl
II
, Wang
III
, and dual linker
IV
(diisopropylsilyl linker and Wang
resin), respectively (Scheme 7.24). Polymer-supported
N
-hydroxycarbamates
171
oxidized in the presence of cyclic and linear dienes including 1,3-cyclohexadiene, 2,4-
hexadiene, cycloheptatriene and 9,10-dimethylanthracene resulted in diverse oxazine-
based derivatives
172
to
180
. Diels-Alder reactions of arylnitroso compounds were
also investigated [49].
Extensive research focused on the discovery of novel compounds with anti-MRSA
(methicillin-resistant
Staphylococcus aureus
) activity [50,51]. 242 Derivatives of 18
discrete natural product-like scaffolds were prepared in four steps. The synthesis
was carried out on the resin
181
bearing phosphonate moieties and permitted the
stereoselective formation of
-unsaturated acyl imidazolidinones (Scheme 7.25).
In addition, to expand compound diversity, the imidazolidinone linker could be further
derivatized, hydrolyzed, esterified, reduced, and amidated.
Resin
182
underwent [2
,
3] cycloaddition, dihydroxylation, or Diels-Alder
cycloaddition to yield intermediates
183
to
185
. Pyrrolidine intermediate
183
was
further either acylated or underwent reductive amination to afford final compounds
186
and
187
. Diol
184
was transformed into four different products. Treatment with
SOCl
2
, NaN
3
, and DMAD led to triazole
188
. O-Alkylation yielded diether
189
,
while condensation with carbonyl derivatives afforded ketals
190
and acetals
191
.
Cycloadduct
185
underwent oxidation to bridged scaffold
192
or metathesis to yield
cyclopentane derivative
193
. Alternatively, it was oxidized to derivative
194
, which
was further converted into four diverse scaffolds
197
to
200
. Finally, intermediate
185
was transformed into products of metathesis
195
and
196
.
+
7.2.2 Substrate-Based Strategy: Folding Process
The folding approach is based on the transformation of a common precursor bearing
various appending substituents (
-elements) into different skeletons under identical
reaction conditions. An illustrious example of this approach is the work by Burke
et al. [52]. They have prepared three precursors having different
-elements in a
few reaction steps using macrobeads as a solid support. Furan precursors
201
to
203
(Scheme 7.26) were exposed to the same reaction conditions: treatment with
NBS, followed by reaction with PPTS. As a result, three diverse skeletons, which
included 1260 individual compounds, were synthesized. Compounds were prepared
in all possible combinations of building blocks and encompassed skeletal diversity.
While precursors
201
and
203
afforded the anticipated products [3.2.1]bicyclic
ketal
204
and (
E
)-enedione
206
, precursor
202
underwent an initial oxidative ring
expansion to cyclic hemiketal followed by unexpected, acid-mediated dehydration to
yield pyranyl derivative
205
.
