Progress in the Chemistry of Cytochalasans
105
obtained was oxidized to aldehyde F14 and ready for HWE macro-ring-closure. The
macrolactone F15 was generated in 65% yield by the use of NaOCH 2 CF 3 as a
base in CF 3 CH 2 OH and DME. Deprotection of N-Boc followed by hydrolysis of
the tert-butyldimethylsilyl ether afforded compound F16, in which the epoxide was
transformed into allylic alcohol to deliver the final product cytochalasin B (110).
5.2.2 Total Synthesis of L-696,474
Starting with the same intermediate F8 mentioned above, it was possible to synthesize the HIV-1 protease inhibitor L-696,474 (26) [35, 276] (Scheme 9). After the
removal of the N-Boc group, it was then oxidized to the imine F24 by use of
[bis(trifluoro-acetoxy)iodo]benzene. Then, this was converted to an aldehyde by a
non-hydrolytic opening strategy followed by spontaneous intramolecular transamination and hydrolysis. The crude aldehyde was directly converted to the methyl ester
F25 by treatment with potassium hydroxide and iodine in methanol. After epoxidation and the oxidation of the primary alcohol, the resultant aldehyde F26 was reacted
with another precursor F33, which was synthesized as shown in Scheme 9B. The
ester obtained was treated with lithium dimethyl methylphosphonate followed by
cleavage of the TBS group and oxidation of the resultant primary alcohol to afford
the aldehyde F27, which was ready for the stage of macrocyclization through an
intramolecular HWE reaction. The macrocyclization proceeded smoothly from the
treatment of NaOCH 2 CF 3 as a base in hot dimethoxyethane (80°C) containing 2,2,2trifluroroethanol to afford the tricyclic ketone F28. [274] Stereoselective reduction
of the ketone followed by acetylation then afforded the intermediate F29, which was
converted to L-696,474 (26) after exposure to magnesium sulfate in warm benzene.
5.3 Total Syntheses of Periconiasins A–E
Periconiasins A–C (404–406, Fig. 24), bearing an unprecedented 5/6/9 tricyclic
medium-size ring, were reported by Dai and coworkers from the endophytic fungus
Periconia sp. F-31 in 2013 [182]. More intriguingly, several structurally relevant
congeners were also identified by the same laboratory in 2015, as exemplified by
periconiasins D–F (408–410, Fig. 24) [183, 184]. Different from previously identified cytochalasans, periconiasins D–F (408–410) possess highly complex polycyclic
architectures bearing multiple stereogenic centers. Biological studies have shown
that some periconiasin derivatives display selective cytotoxicity against the HCT-8
and BGC-823 cell lines, thus being of some interest in antineoplastic drug development. The collective total syntheses of periconiasins A–E (408–410, 408, and 409)
have been achieved by Tang and coworkers through a highly efficient and biomimetic
strategy [277].
The synthesis (Scheme 10) commenced from the alkylation 2-methylcyclohexane1,3-dione G1 followed by partial reduction and mesylation to afford compound G3
105
obtained was oxidized to aldehyde F14 and ready for HWE macro-ring-closure. The
macrolactone F15 was generated in 65% yield by the use of NaOCH 2 CF 3 as a
base in CF 3 CH 2 OH and DME. Deprotection of N-Boc followed by hydrolysis of
the tert-butyldimethylsilyl ether afforded compound F16, in which the epoxide was
transformed into allylic alcohol to deliver the final product cytochalasin B (110).
5.2.2 Total Synthesis of L-696,474
Starting with the same intermediate F8 mentioned above, it was possible to synthesize the HIV-1 protease inhibitor L-696,474 (26) [35, 276] (Scheme 9). After the
removal of the N-Boc group, it was then oxidized to the imine F24 by use of
[bis(trifluoro-acetoxy)iodo]benzene. Then, this was converted to an aldehyde by a
non-hydrolytic opening strategy followed by spontaneous intramolecular transamination and hydrolysis. The crude aldehyde was directly converted to the methyl ester
F25 by treatment with potassium hydroxide and iodine in methanol. After epoxidation and the oxidation of the primary alcohol, the resultant aldehyde F26 was reacted
with another precursor F33, which was synthesized as shown in Scheme 9B. The
ester obtained was treated with lithium dimethyl methylphosphonate followed by
cleavage of the TBS group and oxidation of the resultant primary alcohol to afford
the aldehyde F27, which was ready for the stage of macrocyclization through an
intramolecular HWE reaction. The macrocyclization proceeded smoothly from the
treatment of NaOCH 2 CF 3 as a base in hot dimethoxyethane (80°C) containing 2,2,2trifluroroethanol to afford the tricyclic ketone F28. [274] Stereoselective reduction
of the ketone followed by acetylation then afforded the intermediate F29, which was
converted to L-696,474 (26) after exposure to magnesium sulfate in warm benzene.
5.3 Total Syntheses of Periconiasins A–E
Periconiasins A–C (404–406, Fig. 24), bearing an unprecedented 5/6/9 tricyclic
medium-size ring, were reported by Dai and coworkers from the endophytic fungus
Periconia sp. F-31 in 2013 [182]. More intriguingly, several structurally relevant
congeners were also identified by the same laboratory in 2015, as exemplified by
periconiasins D–F (408–410, Fig. 24) [183, 184]. Different from previously identified cytochalasans, periconiasins D–F (408–410) possess highly complex polycyclic
architectures bearing multiple stereogenic centers. Biological studies have shown
that some periconiasin derivatives display selective cytotoxicity against the HCT-8
and BGC-823 cell lines, thus being of some interest in antineoplastic drug development. The collective total syntheses of periconiasins A–E (408–410, 408, and 409)
have been achieved by Tang and coworkers through a highly efficient and biomimetic
strategy [277].
The synthesis (Scheme 10) commenced from the alkylation 2-methylcyclohexane1,3-dione G1 followed by partial reduction and mesylation to afford compound G3