Tricholides A and B and Unnarmicin D: New Hybrid PKS-NRPS Macrocycles Isolated from an Environmental Collection of Trichodesmium thiebautii

Abstract

Bioassay-guided isolation of the lipophilic extract of Trichodesmium thiebautii bloom material led to the purification and structure characterization of two new hybrid polyketide-non-ribosomal peptide (PKS-NRPS) macrocyclic compounds, tricholides A and B ( 1 and 2). A third macrocyclic compound, unnarmicin D ( 3), was identified as a new depsipeptide in the unnarmicin family, given its structural similarity to the existing compounds in this group. The planar structures of 1– 3 were determined using 1D and 2D NMR spectra and complementary spectroscopic and spectrometric procedures. The absolute configurations of the amino acid components of 1– 3 were determined via acid hydrolysis, derivitization with Marfey’s reagent and HPLC-UV comparison to authentic amino acid standards. The absolute configuration of the 3-hydroxydodecanoic acid moiety in 3 was determined using a modified Mosher’s esterification procedure on a linear derivative of tricharmicin ( 4) and additionally by a comparison of ¹³C NMR shifts of 3 to known depsipeptides with β-hydroxy acid subunits. Tricholide B ( 2) showed moderate cytotoxicity to Neuro-2A murine neuroblastoma cells (EC ₅₀: 14.5 ± 6.2 μM).