Synthetic studies toward amphidinol 3.

Amphidinol 3 (AM3) is a polyketide-derived natural product, produced by the marine dinoflagellate Amphidinium klebsii, that displays anti-fungal activity against Aspergillus niger. As a result of this biological activity and its complex architecture, AM3 has received considerable attention from the synthetic community. Our approach to AM3 highlights the double-allylboration methodology developed within our laboratory for the synthesis of 1,5-diols. This method has previously been utilized for the synthesis of two 1,5-diol units found within the acyclic polyol region of AM3. Our general strategy for the bis-THP core of AM3 involves cyclization of a 1,5-diol to provide a dihydropyran, which can be transformed to the two pyran containing fragments of AM3. We have employed a base-mediated cyclization of a functionalized 1,5-diol to provide a common dihydropyran intermediate, which is then further elaborated to give the stereochemically identical C(31)-C(40) and C(43)-C(52) tetrahydropyrans of AM3. Conversion of this common pyran intermediate to the C(26)-C(42) and C(43)-C(67) fragments was completed in 9 steps and 12 steps, respectively. Model systems for coupling of these fragments and efforts toward the total synthesis of AM3 are described.PhDOrganic chemistryPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/126714/2/3276181.pd