Total Synthesis of Fijiolide A

Abstract

Fijiolide A is a secondary metabolite isolated from a marine-derived actinomycete of the genus Nocardiopsis. It was found to significantly reduce the TNF-α induced activity of the transcription factor NFκB, which is considered a promising target for the treatment of cancer and inflammation-related diseases. We disclose an enantioselective synthesis of fijiolide A enabled by a fully intermolecular, yet regioselective cyclotrimerization of three unsymmetrical alkynes to construct its tetra-substituted arene core. An atropselective macroetherification enables the assembly of the strained [2.6]paracyclophane motif. A late-stage glycosylation of the macrocyclic aglycone at its tertiary alcohol position allowed for the first total synthesis of fijiolide A.

Marine natural products

“…63) along with the known and related rifamycin congeners salinisporamycin, 92 and salinketals A and B, 93 were reported. Other total syntheses of marine bacterial metabolites include (AE)-spiroindimicins B and C, 94 bacilosarcin C, 95 cyclomarins A 96 and D, 97 cyclomarazines A and B, 98 nitropyrrolins A, B and D, 99 actinophenanthroline A, 100,101 jiolide A, 102 heronamides A-C, 103 dermacozines A-C. 104 The proposed chemical structure of marineosin A was also successfully synthesised; the structure of the target compound was established following X-ray data analysis. 105 While the NMR data of the synthetic compound showed a high degree of similarity with the previously reported natural product, there were also noticeable differences.…”