5-Amino-2-furancarboxylic acid methyl ester undergoes a facile
Diels−Alder cycloaddition with a
variety of dienophiles to afford ring-opened cycloadducts that are
readily dehydrated using BF3·
OEt2 to give polysubstituted anilines. In each case,
the cycloaddition proceeds with high
regioselectivity, with the electron-withdrawing group being located
ortho to the amino group. The
most favorable FMO interaction is between the HOMO of the furanamine
and the LUMO of the
dienophile. The atomic coefficient at the ester carbon of the
furan is larger than that at the amino
center, and this nicely accommodates the observed regioselectivity.
The [4 + 2]-cycloaddition of
N-(5-nitrofuranyl)morpholine with methyl vinyl ketone
affords a mixture of three phenols. One of
the phenols is derived from a Diels−Alder reaction followed by nitro
group ejection and subsequent
aromatization. The remaining two phenols are the result of
cleavage of the initially formed
oxabicyclic intermediate with concomitant migration of the nitro group.
The mild reaction conditions
with which furan-2-carbamic acid tert-butyl ester undergoes
Diels−Alder cycloaddition with
N-phenylmaleimide allow for the ready isolation of the
initial oxybridged cycloadduct.
The total synthesis and biological evaluation of the resveratrol-derived natural products hopeanol (2) and hopeahainol A (3) in their racemic and antipodal forms are described. The Friedel-Crafts-based synthetic strategy employed was developed from model studies that established the feasibility of constructing the C(7b) quaternary center through an intramolecular Friedel-Crafts reaction and a Grob-type fragmentation to introduce an obligatory olefinic bond in the growing molecule. The final stages of the synthesis involved an epoxide substrate and an intramolecular Friedel-Crafts reaction, followed by oxidation to afford, upon global deprotection, hopeahainol A (3). The latter was converted under basic conditions to hopeanol (2), whereas the reverse transformation, previously suggested as a step in the biosynthesis of hopeahainol A (3), was not observed under a variety of conditions. Biological evaluation of the synthesized compounds confirmed the reported acetylcholinesterase inhibitory activity of hopeahainol A (3) but not the reported cytotoxic potencies of hopeanol (2).
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