Organic Letters
Letter
indole−amine 15 in 73% yield (Scheme 3). Next, we attempted
to construct a seven-membered C-ring.3d Side-chain extension at
the indole β-position in 15 was achieved by treatment with
(COCl)2 in THF. This was accompanied by spontaneous
cyclization to give unstable dicarbonyl compound 16. Finally,
the two carbonyl groups were reduced with BH3·THF to afford
lective attack of the water molecule on C19 position in a plausible
biogenetic intermediate A.
In conclusion, we have succeeded in the asymmetric total
synthesis of a novel skeletal type of indole alkaloid,
kopsiyunnanine E (1), which was newly isolated from Kopsia
arborea, and proved that the natural alkaloid was not
enantiomerically pure.
kopsiyunnanine E (1) [[α]25 −70.0 (c 0.24, CHCl3)] in 50%
D
yield (two steps). Synthetic 1 was identified by comparing its
1
chromatographic behavior and UV, H NMR, 13C NMR, and
ASSOCIATED CONTENT
* Supporting Information
■
S
mass spectra with those of the natural compound. The observed
optical rotation of the synthetic compound having 19S
configuration showed levorotation, similar to the naturalproduct;
however, its specific rotation was very different from that of the
Experimental procedures for the isolation of kopsiyunnanine E
(1) and the preparation of compounds 2, 4−13, 15, 16, synthetic
1, racemic 6, and S1−S3; chiral HPLC analysis of natural,
natural product [[α]25 −14.9 (c 0.06, CHCl3)]. Then, we
1
synthetic (S)-(−)-, and racemic 1; and copies of H and 13C
D
synthesized racemic 1 starting from achiral allyl alcohol 6, and
analyzed the enantiomeric purity of both synthetic ( )-1 and
(S)-(−)-1 (>99% ee) and the natural product using chiral column
chromatography. We found that natural kopsiyunnanine E
contained predominantly the (−)-enantiomer rather than the
(+)-enantiomer in the ratio of 61.6:38.4 (Figure 3). To date,
there are some reports on the alkaloids that exist as a scalemic
mixture (nonracemic mixture of both enantiomers).12
NMR spectral data for compounds 2, 4−13, 15, 16, S1−S3, and
synthetic 1. This material is available free of charge via the
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by JSPS KAKENHI Grant Nos.
25293023 and 26293023.
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REFERENCES
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Figure 3. Chiral HPLC analysis of synthetic ( )-1 (A), synthetic (S)-
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Scheme 4. Possible Biogenetic Route of Kopsiyunnanine E (1)
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Biosynthetically, kopsiyunnanine E (1) might be derived from
geissoschizine via stemmadenine, which coexisted in this plant, as
shown in Scheme 4. The reason why the natural 1 is not
enantiomerically pure is probably due to the nondiastereose-
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dx.doi.org/10.1021/ol502265q | Org. Lett. 2014, 16, 5000−5003