C O M M U N I C A T I O N S
Scheme 1. Proposed Biosynthetic Relations
Methylated versions of 12 failed to undergo the cycloaddition at
ambient temperature. In principle, sterekunthal (4) could be an
isolation artifact. However, since the retro hetero Diels-Alder
reaction requires relatively high temperatures and anthrakunthone
(7) is probably biosynthetically derived from 4, it appears likely
that 4 is truly a natural product.14
In summary, a concise synthesis of racemic pinnatal and
sterekunthal A has been achieved, which probably reflects the
biosynthesis of the natural products. Studies toward their asym-
metric synthesis via Lewis acid-catalyzed intramolecular dynamic
kinetic resolution are well underway. Total syntheses of other
antimalarial naphthoquinones shown in Chart 1 have been achieved
and will be reported in due course.
Acknowledgment. Financial support by Merck & Co. and the
donors of the Petroleum Research Fund, administered by the
American Chemical Society (PRF#37520-AC1), is gratefully
acknowledged. The Center of New Directions In Organic Synthesis
is supported by Bristol-Myers Squibb as a sponsoring and Novartis
as a supporting member. We thank Kristina Jenett-Siems for spectra
of authentic pinnatal and sterekunthal A.
Scheme 2. Total Synthesis of (()-Pinnatal and (()-Sterekunthal
Aa
Supporting Information Available: Full experimental details and
spectra for compounds 12-19 and synthetic 1 and 4. This material is
References
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(7) Of course, the order of the oxidation and cyclization events could be
different.
(8) Interestingly, this relationship has not been explicitly stated in the original
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(9) Related reactions occur in the biosynthesis of estrone and other aromatic
steroids.
a Reagents and conditions: (a) (TFEO)2P(O)CH2COOEt, KHMDS,
18-C-6 (76%); (b) DIBAH (94%); (c) DHP, PPTS (99%); (d) TBAF (90%);
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MeOH (97%); (h) Swern reagent (87%); (i) rt, neat (91%); (j) PhH, 160
°C (92%).
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1
sterekunthal A (4). The H NMR, 13C NMR, IR, and MS spectra
of our synthetic material were in full agreement with data published
for the natural products (see Supporting Information).
The remarkably mild conditions of the Diels-Alder reaction
leading to 1 suggest that this step is indeed biomimetic. We believe
that the reaction is catalyzed by the phenolic hydroxy group of 12.
(14) We predict that compounds analogous to 4 can be isolated from natural
sources containing 2 and 3.
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