Three diterpene-benzoate natural products, with novel carbon skeletons and an unusual proposed biosynthesis, were isolated from extracts of the Fijian red alga Callophycus serratus and identified by a combination of X-ray crystallographic, NMR, and mass spectral analyses. Bromophycolide A (1) displayed cytotoxicity against several human tumor cell lines via specific apoptotic cell death. This represents the first discovery of natural products incorporating a diterpene and benzoate skeleton into a macrolide system.The discovery of novel carbon skeletons in natural products research is uncommon, providing new targets for synthetic chemists and pharmacologists, and leading to testable hypotheses regarding biosynthetic mechanisms and ecological function. Red macroalgae are well-known for the production of brominated metabolites, including terpenoids and phenols, yet some taxa within the Rhodophyta remain relatively unstudied. Only six secondary metabolites, one oxylipin and five bromophenols, have been previously characterized from the red algal family Solieriaceae. 1,2 Herein, we report the discovery of a unique structural class of macrolides from Callophycus serratus, an understudied member of the Solieriaceae.We used bioassay-guided fractionation followed by spectroscopic and X-ray crystallographic analyses to identify three novel natural products (1-3) of unusual biosynthetic origin and possessing promising antineoplastic and antimicrobial activities. Supporting Information Available: Additional acknowledgments, experimental details, 2D NMR data (COSY, HSQC, HMBC, NOESY, ROESY), 1 H NMR spectra for 1-3, and X-ray crystallographic data (tables and CIF files) for 1 and 2. This material is available free of charge via the Internet at http://pubs.acs.org. The most abundant natural product from C. serratus, bromophycolide A (1), displayed an [M -H] − molecular ion with m/z 661.0194 and characteristic tribrominated isotopic pattern, suitable for a molecular formula of C 27 H 37 O 4 Br 3 . X-ray diffraction analysis of 1 revealed a 15-membered macrolide within a diterpene-benzoate framework (Figures 1 and 2). The bromine atom within the isopropyl appendage was disordered with respect to the isopropyl methyls over two primary positions, with 70% and 30% occupancies. The Flack parameter was refined to be −0.002(16), indicating that the geometry shown is the absolute configuration. NIH Public AccessThe NMR spectral data of 1 supported the structure derived from X-ray diffraction analysis (Table 1; Supporting Information). HMBC correlations from the methyl groups anchored the carbon skeleton, enabling assignments of all quaternary carbons. COSY and additional HMBC correlations provided the connectivity within spin systems (Supporting Information).From high-resolution mass spectral data, bromophycolide B (2) appeared to be an isomer of 1, with a parent ion with m/z 661.0191. X-ray diffraction analysis of 2 indicated a 16-membered macrolide with absolute stereochemistry predicted as in Figures 1 and 2. Chemical shift...

Chromophoric (or colored) dissolved organic matter (CDOM) has been identified as a major determinant of the optical properties of oligotrophic oceans. The factors controlling distribution of CDOM far from the direct influence of land are not well known, as CDOM abundance and distribution does not directly correlate with phytoplankton productivity or biomass, or with dissolved organic matter (DOM) concentration. As part of a larger study of the dynamics of CDOM in the open ocean, we investigated direct release from plankton as a factor contributing to distribution patterns of CDOM. We measured the production of CDOM by zooplankton (copepods, euphausiids, amphipods, salps, polychaetes), protozoans (colonial radiolaria), and by the colonial cyanobacterium Trichodesmium spp. in the North Atlantic subtropical gyre. Groups of individual species of plankton were incubated and absorption spectra were obtained for their release products. CDOM was produced by all organisms examined, and absorption spectra varied by taxa, with major taxa exhibiting characteristic absorption peaks. Plankton-produced DOM is a source of labile carbon and thus facilitates microbial activity, and CDOM may also serve as photoprotection for near-surface-living organisms. Zooplankton likely play an important role in the CDOM cycle in the Sargasso Sea, directly through release/excretion of CDOM and indirectly by providing a labile substrate (excretia) for microbial-mediated production of CDOM.KEY WORDS: Zooplankton · Trichodesmium · Chromophoric dissolved organic matter · CDOM · Excretion · Sargasso Sea · North AtlanticResale or republication not permitted without written consent of the publisher