Total synthesis of ningalin C

Abstract

Ningalin C is a polar highly-colored alkaloid isolated in 1997 from dark purple Didemnum sp in Ningaloo Reef region at the northwest cape of Western Australia in the form of Dark-red amorphous powder. As a part of recent research programs in target oriented synthesis, we have investigated the synthesis of ningalin C constituting a general synthetic route to ningalin type marine natural products In this study, the reaction between 5-bromo-3-methyl-2-pyrone and dimethoxy benzyne gave us synthetically useful naphthalene for natural product synthesis. With this naphthalene, we were able to synthesize key intermediates effectively. From those key intermediates, we recently had successfully synthesized ningalin D and G. Recently, we have further extended the above strategy and completed the synthesis of ningalin C. The key to the success was the assembly of the indole through the successive C-N coupling reactions. Functional group transformations, oxidations and necessary substituents allowed the synthesis of the title natural product, ningalin C.