2.5 Summary and Outlook
39
2.5 Summary and Outlook
A one-pot reaction was designed for the synthesis of the intermediate oxime.
This reaction combines three single steps, and utilises TCCA as oxidant.
The one-pot sequence can be carried out at room temperature and affords
the intermediate oxime in 99 % yield (1 mmol batch, 97 % in a 20 mmol
batch). The use of TCCA allowed omission of commonly used PCC, a known
carcinogen. The obtained oxime can be used after aqueous workup, without
further purification.
A palladium catalysed C–H acetoxylation at 40 °C was utilised for the
introduction of the C-23 hydroxy group. Acetoxylation was even successfully
carried out at 20 °C, albeit in low yield. This represents the first example
of catalytic C–H acetoxylation at such low temperatures. Furthermore,
scalability of this reaction was demonstrated in a 20 mmol batch. As the
diastereoselectivity of the C–H acetoxylation is solely substrate controlled,
utilisation of chiral ligands could possibly increase the dr of this transformation.
The deacetylation-deoximation step may be improved by neutralising
excess K 2 CO 3 . The absence of base might disfavour the described retroaldol reactivity. Following this strategy, Berger was able to obtain 65 % yield
in this transformation.
[33]
In summary, the development of a novel semisynthetic approach to hederagonic acid (1) was presented. Deployment of carefully designed one-pot
reactions allowed the shortening of the synthetic sequence, resulting in the
to date shortest route to hederagonic acid (1).
At last, the herein synthesised β-hydroxy ketone intermediate 8b could
serve as branching point for the syntheses of more complex oleananes
(Scheme 2.26). As example, further functionalisation at C-2 can lead to
arjunolic acid (33a) and bayogenin (33b).
[1] Potential modifications at C-6
would allow access to higher members of the oleanane family, like uncargenin
C (33c) and terminolic acid (33d). The versatile biological activities of
these natural products, combined with their utterly limited commercial
availability, makes them interesting targets in natural product synthesis.
39
2.5 Summary and Outlook
A one-pot reaction was designed for the synthesis of the intermediate oxime.
This reaction combines three single steps, and utilises TCCA as oxidant.
The one-pot sequence can be carried out at room temperature and affords
the intermediate oxime in 99 % yield (1 mmol batch, 97 % in a 20 mmol
batch). The use of TCCA allowed omission of commonly used PCC, a known
carcinogen. The obtained oxime can be used after aqueous workup, without
further purification.
A palladium catalysed C–H acetoxylation at 40 °C was utilised for the
introduction of the C-23 hydroxy group. Acetoxylation was even successfully
carried out at 20 °C, albeit in low yield. This represents the first example
of catalytic C–H acetoxylation at such low temperatures. Furthermore,
scalability of this reaction was demonstrated in a 20 mmol batch. As the
diastereoselectivity of the C–H acetoxylation is solely substrate controlled,
utilisation of chiral ligands could possibly increase the dr of this transformation.
The deacetylation-deoximation step may be improved by neutralising
excess K 2 CO 3 . The absence of base might disfavour the described retroaldol reactivity. Following this strategy, Berger was able to obtain 65 % yield
in this transformation.
[33]
In summary, the development of a novel semisynthetic approach to hederagonic acid (1) was presented. Deployment of carefully designed one-pot
reactions allowed the shortening of the synthetic sequence, resulting in the
to date shortest route to hederagonic acid (1).
At last, the herein synthesised β-hydroxy ketone intermediate 8b could
serve as branching point for the syntheses of more complex oleananes
(Scheme 2.26). As example, further functionalisation at C-2 can lead to
arjunolic acid (33a) and bayogenin (33b).
[1] Potential modifications at C-6
would allow access to higher members of the oleanane family, like uncargenin
C (33c) and terminolic acid (33d). The versatile biological activities of
these natural products, combined with their utterly limited commercial
availability, makes them interesting targets in natural product synthesis.