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.