Communication
and 13C NMR spectroscopic data. Inspection of these data re-
veals that the synthetic data do not match that reported for
natural phomolide G.[3a] This data[4b] is recorded in a solvent
different to that of the natural product.[3a] We have recorded
the spectra of both compounds 1 and 33 in the original me-
dium,[3a] as well as in that reported by Reddy and co-work-
ers,[4b] confirming the mismatch. The NMR spectroscopic data
of compounds 1 and 33 do not match the data reported by
Reddy and co-workers, while that of compound 33 is identical
to that of the natural product (Table 1). Additionally, compound
23 reported above (Scheme 3), the structure of which is secured
according to the sequence 23 → 24 → 25 (X-ray analysis) is
reported as a late-stage intermediate in the synthesis of Reddy
and co-workers, the 1H and 13C NMR spectroscopic data of
which[4b] do not match with this structure.
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Conclusions
We report an asymmetric synthesis of the macrolactone 1, the
putative structure originally assigned to the natural nonenolide
(–)-phomolide G,[3a] the H and 13C NMR spectroscopic data of
1
which do not match that of the natural product. We also report
the asymmetric synthesis of the C3-epimeric nonenolide 33,
the data of which proved to be an identical match to that of
natural (–)-phomolide G. The structure of the natural product
should thus be revised to compound 33, and this work there-
fore represents the first report on the total synthesis and struc-
ture of this natural nonenolide. The general synthetic strategy
reported permits synthesis of all diastereomers of the phomol-
ide nonenolide core at positions 3 and 9, while use of D-tartrate
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or other carbohydrate-derived C4-chirons should allow access
to diastereomers equivalent to 13. The pivotal terminal olefin
introduced here as in 11 is designed to allow access to homolo-
gous analogs such as seimatopolide (3) by cross-metathesis or
hydroboration/cross-coupling sequences. The synthesis of a se-
ries of diastereomers and homologs based on this general syn-
thetic strategy and detailed investigation of their biological ac-
tivities is under active investigation in our laboratories.
CCDC 1439915 (for 25) contains the supplementary crystallographic
Acknowledgments
We thank the Natural Sciences and Engineering Council of
Canada, Cytec Canada, the Ontario Centres of Excellence, and
Connect Canada for financial support of this work.
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Keywords: Polyketides · Asymmetric synthesis ·
Nonenolides · Total synthesis · Macrolactones
[1] The nonenolide class of macrolactones are also referred to as de-
canolides; for general reviews, see: a) G. Drager, A. Kirschning, R. Thier-
icke, M. Zerlin, Nat. Prod. Rep. 1996, 13, 365–375; b) V. B. Riatto, R. A.
Pilli, M. M. Victor, Tetrahedron 2008, 64, 2279–2300.
Received: November 27, 2015
Published Online: January 15, 2016
Eur. J. Org. Chem. 2016, 688–692
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