The organocatalytic three-step total synthesis of (+)-frondosin BElectronic supplementary information (ESI) available: Experimental procedures and spectral data for all new compounds; interview with David MacMillan. See DOI: 10.1039/c0sc00204f

• Main Authors: Reiter, Maud, Torssell, Staffan, Lee, Sandra, MacMillan, David W. C
• Format: Journal Article
• Language: English
• Published: 07.06.2010
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c0sc00204f

The frondosins are a family of marine sesquiterpenes isolated from the sponge Dysidea frondosa that exhibit biological activities ranging from anti-inflammatory properties to potential application in anticancer and HIV therapy. Herein, a concise enantioselective total synthesis of (+)-frondosin B is described which requires a total of three chemical steps. The enantioselective conjugate addition of a benzofuran-derived boronic acid to crotonaldehyde in the presence of an imidazolidinone organocatalyst builds the critical stereogenic center of frondosin B in the first operation, while the remaining two ring systems of this natural product are installed in the two subsequent steps. A combination of X-ray crystallographic data, deuterium labeling, and chemical correlation studies provides further evidence as to the correct absolute stereochemical assignment of (+)-frondosin B. A concise enantioselective total synthesis of (+)-frondosin B is described which requires a total of three chemical steps. X-Ray crystallographic data, deuterium labeling, and chemical correlation studies provide evidence as to the correct absolute stereochemical assignment of (+)-frondosin B.