We report a highly stereocontrolled total synthesis of one of the possible stereoisomers of laurenidificin. Highlights of the synthesis include the formation of the 2,6-dioxabicyclo[3.3.0]octane framework by a stereospecific bromolactonization-α-bromination-ring contraction sequence, followed by a stereoselective propargylation, an insertion of the Z-enyne side chain by a hydroindation/cross coupling reaction, and ethylation at C13 with an organocuprate reagent. While the synthetic compound was not identical to the natural product, the absolute stereochemistry of the natural product was proposed on the basis of NMR analyses. Moreover, a formal total synthesis of (+)-aplysiallene was achieved by extending the ring contraction strategy.
We report the first
total syntheses of (+)-isolaurenidificin (1) and (−)-bromlaurenidificin
(2), the
latest acetogenins of the 2,6-dioxabicyclo[3.3.0]octane class. The
synthesis features a completely stereoselective one-pot epimerization-ring
contraction to establish the cis configuration with respect to C10–H
and C12–H of the tetrahydrofuran ring. Six stereogenic centers
and an olefin geometry were constructed in a highly stereoselective
manner. Absolute configurations of the natural products were deduced
by the comparison of NMR data and specific rotations.
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