Progress in the Chemistry of Cytochalasans
113
generated asperchalasines B–E (448–451) (10:2:1:1) in a combined yield (80%).
Interestingly, if the fully protected hemiacetal I15 was used in the reaction, only
two endo-type products, asperchalasines E and D (451 and 450) (57%, 3:2), were
detected after debenzylation (Scheme 15). A similar outcome was obtained with
I16, affording two endo-adducts I19 and I20 in excellent combined yield (80%,
3:2). Finally, the biomimetic oxidative formal [5 + 2]-cycloaddition [293, 294] was
achieved to deliver asperchalasine A (455) (Scheme 16) after debenzylation of I19
with Raney Ni/H 2 followed by directly exposed to air in the presence of aspochalasin
B (344).
5.5.2 Total Synthesis of Asperchalasines A, D, E, and H by Deng’s
Group
Concurrent with the work of Tang and associates, the group of Deng, from the
Kunming Institute of Botany, also reported independently the total syntheses of
asperchalasines A (455), D (450), E (451), and H (454). Deng’s synthesis started
with the stereospecific preparation of the triene segment J4 (Scheme 17). Initially,
the l-arabinose was converted to hemiacetal J1 through a known three-step sequence
[295]. After sequential Wittig olefination, silylation protection, and hydrogenation
of the resulting double bond, the methyl ketone J2 was obtained in 69% yield. This
was then coupled with the dienyl phosphonate J3 to afford the conjugated triene J4
(82%, (E)/(Z) = 7:1). The known lactam J5 [186], prepared from N-Boc-l-leucine
in five steps, was reacted with methyl chloroformate, affording the methyl ester J6.
After sequential selenylation and oxidative elimination, it was transformed into the
activated dienophile J7. A mixture of J7 and J4 was heated to 100 °C to furnish
the Diels–Alder products J8 and its isomer (85%, ((E)/(Z) = 2:1) [296]. The addition of lithium dimethyl methylphosphonate followed by selective deprotection and
oxidation of the resultant primary alcohol yielded the aldehyde J9. The HWE macrocyclization was accomplished by the use of Zn(OTf) 2 [297]. After deprotection of the
TBS group followed by selective oxidation, aspochalasin D (346) and aspochalasin
B (344) were obtained in overall 79% and 72% yields, respectively.
Then, aspochalasin B (344) was added to the active diene, which was generated
in situ by the acidic treatment with J10, affording the endo-Diels–Alder adducts
J12 and its regioisomer J13 in 78% yield (Scheme 18) [298, 299]. Both adducts
were subjected to deallylation to furnish J14 and asperchalasine H (454). Similarly, asperchalasines D (450) and E (451) also could be obtained using the same
sequence for the synthesis of asperchalasine H (454) in 73% overall yield as shown
in Scheme 18B. Treatment of J14 with potassium ferricyanide led to facile oxidation
of the electron-rich aromatic ring to yield the corresponding o-quinone, which was
unstable and trapped by another molecule of aspochalasin B (344) in the presence of
sodium bicarbonate to furnish the formal the [5 + 2] adduct asperchalasine A (455)
in 49% yield [300].
113
generated asperchalasines B–E (448–451) (10:2:1:1) in a combined yield (80%).
Interestingly, if the fully protected hemiacetal I15 was used in the reaction, only
two endo-type products, asperchalasines E and D (451 and 450) (57%, 3:2), were
detected after debenzylation (Scheme 15). A similar outcome was obtained with
I16, affording two endo-adducts I19 and I20 in excellent combined yield (80%,
3:2). Finally, the biomimetic oxidative formal [5 + 2]-cycloaddition [293, 294] was
achieved to deliver asperchalasine A (455) (Scheme 16) after debenzylation of I19
with Raney Ni/H 2 followed by directly exposed to air in the presence of aspochalasin
B (344).
5.5.2 Total Synthesis of Asperchalasines A, D, E, and H by Deng’s
Group
Concurrent with the work of Tang and associates, the group of Deng, from the
Kunming Institute of Botany, also reported independently the total syntheses of
asperchalasines A (455), D (450), E (451), and H (454). Deng’s synthesis started
with the stereospecific preparation of the triene segment J4 (Scheme 17). Initially,
the l-arabinose was converted to hemiacetal J1 through a known three-step sequence
[295]. After sequential Wittig olefination, silylation protection, and hydrogenation
of the resulting double bond, the methyl ketone J2 was obtained in 69% yield. This
was then coupled with the dienyl phosphonate J3 to afford the conjugated triene J4
(82%, (E)/(Z) = 7:1). The known lactam J5 [186], prepared from N-Boc-l-leucine
in five steps, was reacted with methyl chloroformate, affording the methyl ester J6.
After sequential selenylation and oxidative elimination, it was transformed into the
activated dienophile J7. A mixture of J7 and J4 was heated to 100 °C to furnish
the Diels–Alder products J8 and its isomer (85%, ((E)/(Z) = 2:1) [296]. The addition of lithium dimethyl methylphosphonate followed by selective deprotection and
oxidation of the resultant primary alcohol yielded the aldehyde J9. The HWE macrocyclization was accomplished by the use of Zn(OTf) 2 [297]. After deprotection of the
TBS group followed by selective oxidation, aspochalasin D (346) and aspochalasin
B (344) were obtained in overall 79% and 72% yields, respectively.
Then, aspochalasin B (344) was added to the active diene, which was generated
in situ by the acidic treatment with J10, affording the endo-Diels–Alder adducts
J12 and its regioisomer J13 in 78% yield (Scheme 18) [298, 299]. Both adducts
were subjected to deallylation to furnish J14 and asperchalasine H (454). Similarly, asperchalasines D (450) and E (451) also could be obtained using the same
sequence for the synthesis of asperchalasine H (454) in 73% overall yield as shown
in Scheme 18B. Treatment of J14 with potassium ferricyanide led to facile oxidation
of the electron-rich aromatic ring to yield the corresponding o-quinone, which was
unstable and trapped by another molecule of aspochalasin B (344) in the presence of
sodium bicarbonate to furnish the formal the [5 + 2] adduct asperchalasine A (455)
in 49% yield [300].