Organic Letters
Letter
a
4
Scheme 2. Total Synthesis of (−)-Angiopterlactone B (1),
plants, is a likely biosynthetic precursor to natural
(+)-angiopterlactone B (1).
9
Its X-ray Crystal Structure, and Diagnostic Upfield Region
1
of the Crude H NMR Spectrum for the Dimerization
In summary, a scalable, protecting-group-free, enantioselec-
tive total synthesis of (−)-angiopterlactone B (1) has been
achieved in four steps. Our experimental results indicate that
Reaction
(
+)-angiopterlactone B (1) is likely the result of an inherently
12
selective dimerization of the aglycone of angiopteroside (8).
Detailed mechanistic studies, both experimental and computa-
tional, are currently underway in our laboratory to investigate
the reactivity and selectivity of this dimerization process and
will be reported in due course.
ASSOCIATED CONTENT
Supporting Information
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*
S
Experimental procedures and analytical data for all
AUTHOR INFORMATION
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*
ORCID
Author Contributions
‡
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work was supported by a Royal Society Research Grant
and a Marie Curie Career Integration Grant. M.I.T. thanks the
University of Edinburgh for the provision of a studentship. Dr.
Patrick Brown (University of Edinburgh) and Ellen Rykers
(Australian National University) are thanked for conducting
preliminary experiments.
a
Yields are reported as a range, representing the isolated yields
obtained from several reactions. The reaction scale corresponds to the
approximate quantity of product isolated from a single reaction.
REFERENCES
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(
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(2) For examples of the domino oxa-Michael/Michael reaction
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1
details). Nevertheless, analysis of the H NMR spectrum of the
crude dimerization product (see Scheme 2) revealed a
remarkably selective reaction with δ-lactone 4, γ-lactone 3,
and γ-lactone 7 (presumably formed through base-mediated
epimerization of γ-lactone 3) accounting for the majority of the
remaining material. When the three monomeric lactones (4, 3,
and 7) are present, there are a total of 72 dimeric structures
that could conceivably form through a domino oxa-Michael/
4
(
Tang, Y. Org. Lett. 2012, 14, 4878−4881. (e) Brown, P. D.; Willis, A.
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10
Michael reaction sequence. It is, therefore, fascinating that we
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̃
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An [α]2 of +22 (c 0.04, EtOAc) is reported for natural
0
1
D
2
0
angiopterlactone B (1), whereas an [α] of −25 (c 0.04,
EtOAc) was obtained for our synthetic material. Therefore, it
D
(
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2
must be concluded that the absolute configuration of natural
11
(
+)-angiopterlactone B (1) needs revision. Importantly, this
(
reveals that angiopteroside 8 (see Scheme 1), a glycoside
natural product previously isolated from various Angiopteris
Chem. 1981, 37, 2095−2098. (b) Taveenpanich, S.; Kamthong, N.;
Sawasdipuksa, N.; Roengsumran, S. J. Sci. Res. Chula. Univ. 2005, 30,
B
Org. Lett. XXXX, XXX, XXX−XXX