Toward a Formal Synthesis of Laureatin: Unexpected Rearrangements Involving Cyclic Ether Nucleophiles

Laureatin, a metabolite of the red algae Laurencia
nipponica, has shown potent activity as a mosquito larvicide.
The two previously published syntheses of laureatin involved an initial
preparation of the 8-membered cyclic ether, followed by formation
of the oxetane ring. Our strategy was the reverse, i.e., to utilize
an oxetane as the framework to construct the larger ring. During this
work, attempted N-bromosuccinimide (NBS)-mediated
cyclization of oxetane alcohol 17, prepared from readily
accessible 2-methyleneoxetane 12, yielded epoxytetrahydrofuran 19 rather than the expected laureatin core. Further derivatization
of 19 yielded trans fused bis-tetrahydrofuran 32. The synthesis of 19 and 32,
as well as structural and stereochemical elucidation studies, are
described.