Approaches to the enantioselective synthesis of falcarindiol

ORGN 661

Michael R. Shepard Jr., mrshepar@iupui.edu1, Nathan A. Furr1, and Robert E. Minto, rminto@iupui.edu2. (1) Department of Chemistry and Chemical Biology, Indiana University - Purdue University Indianapolis, 402 N. Blackford Street, Indianapolis, IN 46202, (2) Department of Chemistry and Chemical Biology, Indiana University Purdue University Indianapolis, 402 N. Blackford St., LD 326, Indianapolis, IN 46202
(S,S)-Falcarindiol (1) is a widely distributed bioactive polyacetylene with antifungal, neurotoxic, and anti-inflammatory activities that accumulates in plants of the Apiaceae family. We have developed two synthetic paths to 1 as part of our biosynthetic studies for the diacetylene, and will contrast our methods and those reported by others. In our studies, one approach began with inexpensive isoascorbic acid, a chiral pool source, and the other employed a high-yielding asymmetric dihydroxylation chemistry to enantioselectively form propargylic alcohol 2. A dinuclear zinc-catalyzed addition to a variety of α,β-unsaturated aldehydes provided 3, allowing cross-coupling for the convergent synthesis of 1.