Biomedical Engineering Reference
In-Depth Information
Me
Me
OMOM
OMOM
MnO
2
CH
2
Cl
2
, rt
HO
OH
O
O
O
O
Et
3
N
-25 to 45°C
MOMO
MOMO
416
417
OH
OMOM
O
O
Me
OH
Me
OH
H
H
OH
OMOM
Deprotection
O
O
H
H
MOMO
HO
O
O
Me
Me
HO
HO
O
O
HO
MOMO
(+)-Rugulosin
419
418
SCHEME 9.73
Synthesis of (+)-rugulosin
419
by Nicolaou and coworkers.
the initial hemiacetal
410
, which was oxidized to the ketoaldehyde
412
via
411
.
412
413
Compound
with the addition of one molecule
of water in 82% overall yield for this three-step domino process. For the total
synthesis of both CP-263114 (
407
) and CP-225917 (
408
),themoreadvanced
intermediate
415
bearing an additional maleic anhydride ring obtained from
413
via
414
was finally converted to diol
was used [160].
The bisanthraquinones are a growing class of natural products that have been
isolated from a wide range of sources. Belonging to this group, (
)
is present in
P. rugulosum
, the penicillia contaminating rice, maize, and cereal
crops [161]. The compound has been studied in a variety of biological assays and
reported to be highly toxic in a range of cell lines, and it forms complexes with DNA.
Additionally, anti-HIV properties of this bisanthraquinone have also attracted the
synthetic chemists. In the key bond forming process of Nicolaou's synthesis of
þ
)-rugulosin (
419
419
,
enantiopure
416
was initially oxidized using MnO
2
to give the corresponding
anthraquinone
417
, which immediately underwent dimerization to afford
418
.
Upon treatment with concentrated HCl,
the latter was finally converted to
(
) (Scheme 9.73) [162].
Whereas the natural
D
-sugars are readily available, the synthesis of the corre-
sponding
L
-sugars requires efforts. Nonetheless, they are interesting startingmaterials
for the synthesis of complex natural products and bioactive molecules. Hence, the
development of efficient procedures that allow a straightforward access to these
compounds has become particularly important. Guaragna and coworkers developed a
domino process toward
L
-allose (
þ
)-rugulosin (
419
425
422
) and
L
-glucose (
) consisting of five synthetic
420
steps (Scheme 9.74) [163]. Thus, treatment of
with DDQ led to the 1,6-anhydro
421
sugar derivative
, which could easily be transformed into the desired
L
-glucose and
L
-allose derivatives
422
and
425
, respectively, presumably via
423
and
424
.
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