108
H. Zhu et al.
After sequential selenylation, deprotection, and oxidative elimination, G7 was
converted to G8 as a single (Z)-configured isomer. Next, the introduction of the
hydroxy group was achieved by 1,4-conjugate addition of alcohol, delivering periconiasin A (404) as a single diastereoisomer after removal of the PMB group with
DDQ [280]. The proposed biomimetic transannular carbonyl–ene reaction of periconiasin A (404) was effected under thermal conditions (MeOH, sealed tube, 150°C),
to furnish periconiasin E (409) in 36% yield [281]. Furthermore, periconiasin A
(404) was oxidized to periconiasin C (406) by Dess–Martin oxidation, and it was
then converted into periconiasin B (405) by regio- and diastereoselective reduction
of the C-17 carbonyl group. Periconiasin B (405) was submitted to the reaction
conditions employed for the synthesis of periconiasin E (409), and this resulted in
the direct formation of periconiasin D (408) by tandem transannular carbonyl–ene
reaction/etherification (Scheme 11). Meanwhile, an alternative approach was also
described for periconiasin D (408) in a diastereoselective manner. Initial oxidation
of periconiasin E (409) with DMP produced the corresponding β-hydroxyketone in
83% yield followed by a 1,3-directed reduction in the presence of Me 4 NBH(OAc) 3 to
yield 17-epi-periconiasin E as a single diastereoisomer. Upon treatment with TsOH,
it was readily converted into periconiasin D (408) by etherification in 80% yield.
5.4 Total Synthesis of Aspochalasins D and B
and (+)-Aspergillin PZ
Aspergillin PZ (398) was first isolated in 2002 by Pei and coworkers from Aspergillus
awamori and has since been re-isolated from several species of Aspergillus as well
as Trichoderma gamsii [171, 176]. In a phenotype assay, aspergillin PZ (398) was
reported to induce morphological deformation of the conidia of P. oryzae at 0.089 mM
[176]. Structurally, it contains a unique pentacyclic skeleton, which features one
quaternary carbon and ten contiguous stereocenters. Its interesting biological activity
combined with the synthesis challenge have inspired great efforts of synthesis
chemists. In 2011, Overman and coworkers reported the first total synthesis of
aspergillin PZ (398) in 28 steps, featuring an unexpected 2-oxonia[3,3]sigmatropic
rearrangement/aldol pathway as shown in Scheme 12 [282].
Quite recently, Trauner and coworkers (Scheme 13) have devised an elegant
biomimetic synthesis of aspergillin PZ (398) in 13 steps [283]. Since it was believed
that aspochalasin D (346) is the likely biogenetic precursor of aspergillin PZ (398)
via a “vinylogous Prins reaction”. The synthesis commenced with the ring-opening
of epoxy alcohol H1 with propargyl magnesium bromide to generate a diol in excellent yield (Scheme 13). Then, a one-pot ozonolysis-reduction sequence followed by
TBS protection provided alkyne H2 in excellent yield over two steps. Silylcupration, alkylative quenching of the in situ generated vinyl cuprate, and treatment of
the resulting vinyl silane with NIS generated vinyl iodide H3. It was then coupled
with H11 by Suzuki coupling to deliver triene H4 [284]. The Diels–Alder reaction
H. Zhu et al.
After sequential selenylation, deprotection, and oxidative elimination, G7 was
converted to G8 as a single (Z)-configured isomer. Next, the introduction of the
hydroxy group was achieved by 1,4-conjugate addition of alcohol, delivering periconiasin A (404) as a single diastereoisomer after removal of the PMB group with
DDQ [280]. The proposed biomimetic transannular carbonyl–ene reaction of periconiasin A (404) was effected under thermal conditions (MeOH, sealed tube, 150°C),
to furnish periconiasin E (409) in 36% yield [281]. Furthermore, periconiasin A
(404) was oxidized to periconiasin C (406) by Dess–Martin oxidation, and it was
then converted into periconiasin B (405) by regio- and diastereoselective reduction
of the C-17 carbonyl group. Periconiasin B (405) was submitted to the reaction
conditions employed for the synthesis of periconiasin E (409), and this resulted in
the direct formation of periconiasin D (408) by tandem transannular carbonyl–ene
reaction/etherification (Scheme 11). Meanwhile, an alternative approach was also
described for periconiasin D (408) in a diastereoselective manner. Initial oxidation
of periconiasin E (409) with DMP produced the corresponding β-hydroxyketone in
83% yield followed by a 1,3-directed reduction in the presence of Me 4 NBH(OAc) 3 to
yield 17-epi-periconiasin E as a single diastereoisomer. Upon treatment with TsOH,
it was readily converted into periconiasin D (408) by etherification in 80% yield.
5.4 Total Synthesis of Aspochalasins D and B
and (+)-Aspergillin PZ
Aspergillin PZ (398) was first isolated in 2002 by Pei and coworkers from Aspergillus
awamori and has since been re-isolated from several species of Aspergillus as well
as Trichoderma gamsii [171, 176]. In a phenotype assay, aspergillin PZ (398) was
reported to induce morphological deformation of the conidia of P. oryzae at 0.089 mM
[176]. Structurally, it contains a unique pentacyclic skeleton, which features one
quaternary carbon and ten contiguous stereocenters. Its interesting biological activity
combined with the synthesis challenge have inspired great efforts of synthesis
chemists. In 2011, Overman and coworkers reported the first total synthesis of
aspergillin PZ (398) in 28 steps, featuring an unexpected 2-oxonia[3,3]sigmatropic
rearrangement/aldol pathway as shown in Scheme 12 [282].
Quite recently, Trauner and coworkers (Scheme 13) have devised an elegant
biomimetic synthesis of aspergillin PZ (398) in 13 steps [283]. Since it was believed
that aspochalasin D (346) is the likely biogenetic precursor of aspergillin PZ (398)
via a “vinylogous Prins reaction”. The synthesis commenced with the ring-opening
of epoxy alcohol H1 with propargyl magnesium bromide to generate a diol in excellent yield (Scheme 13). Then, a one-pot ozonolysis-reduction sequence followed by
TBS protection provided alkyne H2 in excellent yield over two steps. Silylcupration, alkylative quenching of the in situ generated vinyl cuprate, and treatment of
the resulting vinyl silane with NIS generated vinyl iodide H3. It was then coupled
with H11 by Suzuki coupling to deliver triene H4 [284]. The Diels–Alder reaction