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 groupinto the C2-position of an
N-phthaloyl-protected tryptophan (
11). The total synthesis of gypsetin was completedby the dimethyldioxirane-promoted double-oxidative cyclization of a prefashioned diketopiperazine (
19). Totalsyntheses 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-disubstitutedindoles 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 (bearinga prenyl group at the
position of the indole) and
L-proline, was accomplished. The key step involved theintroduction of the prenyl function onto a protected tryptophan congener (
11). A route for the prenylation ofketones with virtually no competitive reverse prenylation is also provided.