32
B. Schmidt
than stagonolide G. By chance, the authors discovered that re-measurement of an
NMR sample of 90 in CDCl 3 gave NMR spectra with an additional set of signals.
The additional set of signals turned out to be a good match for the originally reported
NMR data of stagonolide G. This led to the hypothesis that the ten-membered lactone
90 might undergo an acid-catalyzed rearrangement, which was eventually verified on
a preparative scale by treating the ten-membered lactone 90 with a catalytic amount
of CSA (camphor sulfonic acid). By application of 1D- and 2D-NMR methods, again
in particular by HMBC spectroscopy, the rearrangement product was identified as γbutyrolactone 99. Apart from the value of specific rotation value, all other analytical
data (including the sign of specific rotation) matched those reported for stagonolide
G very well.
Intriguingly, prior to the total synthesis of Angulo-Pachón et al. three other
total syntheses had been reported, which all confirmed the originally assigned tenmembered lactone structure 90 (Table 1, entries 31, 33, 34) [120–122]. In these
cases, the final step of the total synthesis involved a Lewis-acid-mediated or reductive
cleavage of benzyl-protecting groups. Most likely, these deprotection steps proceeded
with a rearrangement to the five-membered lactone, which was not noticed because
its spectral data agreed with those reported for the natural product. Based on the available data, it cannot be excluded conclusively that the actual structure of stagonolide
G is that of a ten-membered lactone 90, which underwent ring contraction to 99
during isolation from the natural source, e.g. promoted by chromatography on acidic
silica gel. The results from the total syntheses only confirmed that the compound
described as stagonolide G in the isolation paper [78] is indeed a γ-butyrolactone
rather than a ten-membered lactone.
A curiosity is, in some regard, how the structure assignment of the recently discovered stagonolide K was accomplished [90]. The constitution and relative configuration were elucidated by HR-ESI-MS, IR-spectroscopy, and 1D- and 2D-NMR
methods. Crystals suitable for single-crystal X-ray analysis were obtained, but in
the absence of any heavy atoms determination of the absolute configuration through
anomalous dispersion is not possible and therefore X-ray analysis could only serve as
a confirmation of the results obtained from NMR analysis. Gratifyingly, Maram et al.
had isolated and characterized a—at that time—non-natural C-9 epimer in the course
of their total synthesis of herbarumin III a few years before [124]. Their synthesis
started from d-ribose, which was converted in six steps into a 3:2 mixture of epimers
of 108. While (R)-108 served as an enantiopure starting material for herbarumin III,
its epimer (S)-108 was converted to 9-epi-herbarumin III in five steps. The product
obtained after ring-closing metathesis turned out to be identical with stagonolide
K (94), including the sign of specific rotation, which led to the assignment of a
(7R,9S)-configuration to stagonolide K (Table 1, entry 39 and Scheme 21).
Curvulide A (95) is the C-4–C-5-epoxide of stagonolide E (88) or of a stagonolide
E epimer. It is covered in this section due to its structural resemblance and possible
structural connection with stagonolide E, although the producing organisms are quite
different: curvulide A (95) was isolated from the marine fungus Curvularia sp., which
is associated with a red alga [79]. Upon its isolation, the structure of curvulide A (95)
could only be partly resolved: a combination of HR-ESI-MS, IR spectroscopy, and
B. Schmidt
than stagonolide G. By chance, the authors discovered that re-measurement of an
NMR sample of 90 in CDCl 3 gave NMR spectra with an additional set of signals.
The additional set of signals turned out to be a good match for the originally reported
NMR data of stagonolide G. This led to the hypothesis that the ten-membered lactone
90 might undergo an acid-catalyzed rearrangement, which was eventually verified on
a preparative scale by treating the ten-membered lactone 90 with a catalytic amount
of CSA (camphor sulfonic acid). By application of 1D- and 2D-NMR methods, again
in particular by HMBC spectroscopy, the rearrangement product was identified as γbutyrolactone 99. Apart from the value of specific rotation value, all other analytical
data (including the sign of specific rotation) matched those reported for stagonolide
G very well.
Intriguingly, prior to the total synthesis of Angulo-Pachón et al. three other
total syntheses had been reported, which all confirmed the originally assigned tenmembered lactone structure 90 (Table 1, entries 31, 33, 34) [120–122]. In these
cases, the final step of the total synthesis involved a Lewis-acid-mediated or reductive
cleavage of benzyl-protecting groups. Most likely, these deprotection steps proceeded
with a rearrangement to the five-membered lactone, which was not noticed because
its spectral data agreed with those reported for the natural product. Based on the available data, it cannot be excluded conclusively that the actual structure of stagonolide
G is that of a ten-membered lactone 90, which underwent ring contraction to 99
during isolation from the natural source, e.g. promoted by chromatography on acidic
silica gel. The results from the total syntheses only confirmed that the compound
described as stagonolide G in the isolation paper [78] is indeed a γ-butyrolactone
rather than a ten-membered lactone.
A curiosity is, in some regard, how the structure assignment of the recently discovered stagonolide K was accomplished [90]. The constitution and relative configuration were elucidated by HR-ESI-MS, IR-spectroscopy, and 1D- and 2D-NMR
methods. Crystals suitable for single-crystal X-ray analysis were obtained, but in
the absence of any heavy atoms determination of the absolute configuration through
anomalous dispersion is not possible and therefore X-ray analysis could only serve as
a confirmation of the results obtained from NMR analysis. Gratifyingly, Maram et al.
had isolated and characterized a—at that time—non-natural C-9 epimer in the course
of their total synthesis of herbarumin III a few years before [124]. Their synthesis
started from d-ribose, which was converted in six steps into a 3:2 mixture of epimers
of 108. While (R)-108 served as an enantiopure starting material for herbarumin III,
its epimer (S)-108 was converted to 9-epi-herbarumin III in five steps. The product
obtained after ring-closing metathesis turned out to be identical with stagonolide
K (94), including the sign of specific rotation, which led to the assignment of a
(7R,9S)-configuration to stagonolide K (Table 1, entry 39 and Scheme 21).
Curvulide A (95) is the C-4–C-5-epoxide of stagonolide E (88) or of a stagonolide
E epimer. It is covered in this section due to its structural resemblance and possible
structural connection with stagonolide E, although the producing organisms are quite
different: curvulide A (95) was isolated from the marine fungus Curvularia sp., which
is associated with a red alga [79]. Upon its isolation, the structure of curvulide A (95)
could only be partly resolved: a combination of HR-ESI-MS, IR spectroscopy, and