The Role of Total Synthesis in Structure …
7
[3]. In this review, Dräger et al. noted that more than 80% of the decanolides known at
that time originate from microbial sources (mostly fungi), where 15% were isolated
from animals and just one decanolide was isolated from a plant, that is, jasmine
ketolactone (1). In 2012, Sun et al. published a second review dedicated to the same
topics that specifically covered the period after publication of the first review by
Dräger et al. until mid-2011 [12]. Sun et al. noted the isolation and description of 63
new decanolides in the chemical literature during this time. Fungi remained the main
source of decanolides. Other reviews were not intended to be comprehensive but
covered specific sub-topics, for example, synthesis studies of specific decanolides
[13].
Since the 1970s, instrumental analytical techniques have seen tremendous
progress, which has changed the strategies used for structure elucidation of natural
products fundamentally. Synthetic interconversion and degradation of novel metabolites to known compounds are used rarely nowadays to assign structures; in particular, because very sensitive high-field NMR spectrometers are routinely available,
and elaborate 1D- and 2D-NMR experiments can be performed in a short time. In
addition, the substantial expansion of ionization techniques available for mass spectrometry facilitates the measurement of high-resolution mass spectra and the reliable
determination of a molecular formula, double-bond equivalents and ring closures.
In light of this technological progress, it appears somewhat surprising that until the
present time the structural assignment of newly isolated decanolides has remained
incomplete occasionally and has turned out to be in part erroneous. This can—as in
Wada’s and Ishida’s case of diplodialide D forty years ago—often be explained by
the very small amounts of new metabolites obtained by isolation from the natural
source, which makes purification and hence interpretation of the NMR spectra often
very difficult. In such cases, the total synthesis of natural products from enantiopure
starting materials with reliably assigned absolute configurations (either obtained exchiral pool or corroborated otherwise) can assist in structure elucidation. This may be
done by proving an assumed structure, by completing structural information (which
is mostly the case when configurations of one or more stereocenters remain elusive
by NMR spectroscopy), or by revising erroneously assigned structures.
Herein, the contribution of total synthesis to the structure elucidation of naturally occurring decanolides is discussed by representative case studies. Results from
isolation studies and investigations into the biosynthesis and bioactivities of certain
compounds will be mentioned briefly, if appropriate, but they are not the primary
focus of this chapter.
2 Recurring Methods in Decanolide Synthesis
In their major review from 1996, Dräger et al. classified synthesis approaches to
decanolides as follows: “(i) oxidative fragmentation of annulated decanolides, (ii)
ring closure by C–C-bond formation, (iii) ring closure by macrolactonization” [3].
7
[3]. In this review, Dräger et al. noted that more than 80% of the decanolides known at
that time originate from microbial sources (mostly fungi), where 15% were isolated
from animals and just one decanolide was isolated from a plant, that is, jasmine
ketolactone (1). In 2012, Sun et al. published a second review dedicated to the same
topics that specifically covered the period after publication of the first review by
Dräger et al. until mid-2011 [12]. Sun et al. noted the isolation and description of 63
new decanolides in the chemical literature during this time. Fungi remained the main
source of decanolides. Other reviews were not intended to be comprehensive but
covered specific sub-topics, for example, synthesis studies of specific decanolides
[13].
Since the 1970s, instrumental analytical techniques have seen tremendous
progress, which has changed the strategies used for structure elucidation of natural
products fundamentally. Synthetic interconversion and degradation of novel metabolites to known compounds are used rarely nowadays to assign structures; in particular, because very sensitive high-field NMR spectrometers are routinely available,
and elaborate 1D- and 2D-NMR experiments can be performed in a short time. In
addition, the substantial expansion of ionization techniques available for mass spectrometry facilitates the measurement of high-resolution mass spectra and the reliable
determination of a molecular formula, double-bond equivalents and ring closures.
In light of this technological progress, it appears somewhat surprising that until the
present time the structural assignment of newly isolated decanolides has remained
incomplete occasionally and has turned out to be in part erroneous. This can—as in
Wada’s and Ishida’s case of diplodialide D forty years ago—often be explained by
the very small amounts of new metabolites obtained by isolation from the natural
source, which makes purification and hence interpretation of the NMR spectra often
very difficult. In such cases, the total synthesis of natural products from enantiopure
starting materials with reliably assigned absolute configurations (either obtained exchiral pool or corroborated otherwise) can assist in structure elucidation. This may be
done by proving an assumed structure, by completing structural information (which
is mostly the case when configurations of one or more stereocenters remain elusive
by NMR spectroscopy), or by revising erroneously assigned structures.
Herein, the contribution of total synthesis to the structure elucidation of naturally occurring decanolides is discussed by representative case studies. Results from
isolation studies and investigations into the biosynthesis and bioactivities of certain
compounds will be mentioned briefly, if appropriate, but they are not the primary
focus of this chapter.
2 Recurring Methods in Decanolide Synthesis
In their major review from 1996, Dräger et al. classified synthesis approaches to
decanolides as follows: “(i) oxidative fragmentation of annulated decanolides, (ii)
ring closure by C–C-bond formation, (iii) ring closure by macrolactonization” [3].