Organic Letters
Letter
Full experimental procedures, characterization data, and
NMR spectra for all new compounds (PDF)
Scheme 8. Assembly of Three Flavan Units via Orthogonal
Activation
AUTHOR INFORMATION
Corresponding Authors
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ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by JSPS KAKENHI Grant Nos.
JP16H06351, JP16H01137, and JP16H04107.
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REFERENCES
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acetal moiety at the C(2) position of the top unit remained
untouched during this coupling reaction.
Finally, all benzyl groups and the bromine atom were
simultaneously removed by hydrogenolysis [H2 (1 atm), 5%
Pd(OH)2/C (ASCA2),11 MeOH−THF−H2O (v/v/v = 4:4:1),
2 h]. Anaerobic filtration through a membrane filter (argon)
gave crude 4 as a pale pinkish amorphous solid, which was
purified by the reverse-phase preparative HPLC (Mightysil RP-
GP II, 20 mm ϕ × 250 mm, MeOH/H2O = 35/65 containing
0.1% TFA) to give pure 4 as an off-white amorphous solid12 in
85% yield.
(4) For synthesis of doubly linked oligomeric flavans, see: (a) Jurd,
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For purpose of characterization, a synthetic sample of 4 was
acetylated (Ac2O, pyridine, rt, 6.5 h), giving the corresponding
(5) Ito, Y.; Ohmori, K.; Suzuki, K. Angew. Chem., Int. Ed. 2014, 53,
10129−10133.
1
peracetate 32 (55% yield from 31). The H and 13C NMR
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spectra of 32 were fully identical with the reported data of the
peracetyl derivative of natural 4,3 confirming the target
structure.
In conclusion, the first total synthesis of selligueain A (4) has
been achieved by exploiting an orthogonal activation method
and annulation for assembly of three flavan components
prepared by de novo syntheses. Further study is in progress on
biological testing using synthetic samples, particularly focusing
attention on sweetness.
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ASSOCIATED CONTENT
* Supporting Information
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Org. Lett. XXXX, XXX, XXX−XXX