A concise and efficient total synthesis of the acyl-CoA:cholesterol acyltransferase inhibitor gypsetin (1) is described. The route features a straightforward method for the introduction of a reverse prenyl group into the C2-position of an N-phthaloyl-protected tryptophan fill. The total synthesis of gypsetin was completed by the dimethyldioxirane-promoted double-oxidative cyclization of a prefashioned diketopiperazine (19). Total syntheses of deoxybrevianamide E (24) and brevianamide E (25) following similar procedures are also described. The reaction of nucleophiles with in situ-generated 3-chloroindolenines provides a route to 2,3-disubstituted indoles from 3-substituted precursors. Indications of the scope and limitations of such reactions are provided. A total synthesis of tryprostatin B (41), a diketopiperazine derived from an L-tryptophan derivative (bearing a prenyl group at the alpha position of the indole) and L-proline, was accomplished. The key step involved the introduction of the prenyl function onto a protected tryptophan congener (11). A route for the prenylation of ketones with virtually no competitive reverse prenylation is also provided.