Total Synthesis of the Chlorinated Pentacyclic Indole Alkaloid (+)-Ambiguine G.

Abstract

Reported herein is the total synthesis of (+)-ambiguine G, the first member of the chlorinated pentacyclic ambiguines to yield to chemical synthesis. The synthesis is accomplished through a convergent strategy that proceeds in 10 steps from (S)-carvone oxide. Pivotal to the concise route is the successful realization of a [4+3] cycloaddition that conjoins two easily synthesized components of the carbon framework of the natural product. Also featured in the synthesis is the efficient, diastereoselective construction of a key vinylated chloro ketone and the unprecedented, one-pot reduction–elimination–oxidation sequence that transforms an enone to an advanced hydroxylated-diene intermediate.