Tandem Reductive Cyclization-Dehydration Approach for the Synthesis of Cryptolepine Hydroiodide and Its Analogues

A new and convenient synthesis of the indoloquinoline alkaloid cryptolepine hydroiodide is described through a tandem reductive cyclization-dehydration approach. This methodology employs a C-C bond formation through the C-2 lithiation of a benzenesulfonyl-protected indole and a C-N bond formation through a nitrene intermediate, which is produced from different organophosphorus reagents, to give a fused tetracyclic compound. The versatility of this method is demonstrated by the syntheses of a series of cryptolepine salts with substituents on the indole as well as the quinoline ring.