Structure Revision of Trichomide D by Total Synthesis

Abstract

A structure revision of trichomide D has been achieved by its total synthesis. The sterically hindered peptide sequence was successfully prepared using not only a conventional amidation with EDCI but also coupling with an Fmoc-protected amino acid chloride derivative. The cyclization precursor was synthesized by coupling of a tetrapeptide with an acylproline derivative and subsequent removal of silyl groups at the N-and Ctermini. Macrolactonization using MNBA/DMAPO followed by preparation of a chlorohydrin moiety furnished the proposed structure of trichomide D, whose spectra were not identical to those of the natural product. Finally, we succeeded in the elucidation of the true structure of trichomide D by its total synthesis, and the absolute configuration of the chlorohydrin moiety was revised to be S. The cytotoxicities of the natural product and its synthetic derivatives against MCF-7 and HeLa S3 cells were evaluated by the MTT method, revealing that the configuration of the chlorohydrin moiety is a pivotal factor for exhibiting potent cytotoxicity against cancer cells.

Marine natural products

“…262 Total synthesis of trichomide D also resulted in revision of the stereochemistry to 821. 263 A convergent synthetic strategy was utilised in the total synthesis of aspergillolide 264 and a biomimetic route was employed in the synthesis of asperoketal A which also provided evidence for the biosynthetic hypothesis proposed. 265 Asymmetric total synthesis of asnovolins A and E utilised anionic fragment coupling to construct the sterically crowded skeleton 266 and solid peptide synthesis was employed to assemble the cyclic pentapeptides, versicotides E and F. 267 Indole diterpenoids (+)-shearinines G and D were prepared via a convergent route.…”

A Survey of Recently Discovered Naturally Occurring Organohalogen Compounds

“…This known metabolite is found in the marinederived fungus Trichothecium roseum IFB-EO66. 93 ■ MARINE BACTERIA Bacteria live and thrive everywhere�including in the marine environment.…”

“…The structure of trichomide D has been revised at the chlorohydrin moiety by total synthesis. This known metabolite is found in the marine-derived fungus Trichothecium roseum IFB-EO66 …”