Collect. Czech. Chem. Commun. 2005, 70, 1696-1708

Formal Total Syntheses of Crocacin A-D

Magnus Besev, Christof Brehm and Alois Fürstner*

Max-Planck-Institut für Kohlenforschung, D-45470 Mülheim/Ruhr, Germany


A concise route to the common polyketide fragment 5 of crocacin A-D (1-4) is presented which has previously been converted into all members of this fungicidal and cytotoxic family of dipeptidic natural products by various means. Our synthesis features a syn-selective titanium aldol reaction controlled by a valinol-derived auxiliary, a zinc-mediated, palladium-catalyzed anti-selective addition of propargyl mesylate 10 to the chiral aldehyde 9, as well as a comparison of palladium-catalyzed Stille and Suzuki cross-coupling reactions for the formation of the diene moiety of the target.

Keywords: Aldol reaction; Alkyne; Cross-coupling reactions; Natural product synthesis; Palladium; Polyketides.

References: 46 live references.