Enantioselective Total Synthesis of Griseocazine D2 & D3

The first enantioselective and biomimetic total syntheses of neuroprotective multiprenylated pyrroloindoline-DKP Griseoca-zine D2, and its diastereomeric congener D3, are reported. The 4-step synthetic route is scalable and convergent, resulting in 24% & 32% overall yields of the congeners, respectively. One of the key features of the synthesis is the installation of both C3 and C3´ normal isoprenyl substituents through a catalytic and highly enantioselective dearomative n-isoprenylation of L-tryptophan. Use of this enantioselective strategy overrides the innate substrate selectivities and thereby requires L-tryptophan as a common precursor for both prenylation and farnesylation steps. DKP formation through the coupling of the two halves occurred without epimerization of the stereogenic alpha center of the amino acids.