TY - JOUR
T1 - Peyssonnosides A-B, Unusual Diterpene Glycosides with a Sterically Encumbered Cyclopropane Motif
T2 - Structure Elucidation Using an Integrated Spectroscopic and Computational Workflow
AU - Khatri Chhetri, Bhuwan
AU - Lavoie, Serge
AU - Sweeney-Jones, Anne Marie
AU - Mojib, Nazia
AU - Raghavan, Vijay
AU - Gagaring, Kerstin
AU - Dale, Brandon
AU - McNamara, Case W.
AU - Soapi, Katy
AU - Quave, Cassandra L.
AU - Polavarapu, Prasad L.
AU - Kubanek, Julia
N1 - Funding Information:
This work was supported by International Cooperative Biodiversity Groups (ICBG) Grant U19-TW007401 from the U.S. National Institutes of Health and the Bill & Melinda Gates Foundation, Seattle, WA Grant OPP1107194. We thank the governments of the Solomon Islands and Fiji for allowing us to perform research in their territorial waters. M. E. Hay, S. Lavoie, J. Kelly, and C. Dell performed collections and photography of algal samples; L. T. Gelbaum provided NMR assistance; D. E. Bostwick and D. Gaul shared expertise for high resolution mass spectrometric analyses; S. Karunakaran helped with acquisition of ORD data; A. Burns and J. Mathew-Valayil performed selected antimicrobial assays; and S. G. Franzblau contributed data from a tuberculosis assay. Enterococcus faecium, strain 513, HM-959 was provided by BEI Resources, NIAID, NIH as part of the Human Microbiome Project.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/7/5
Y1 - 2019/7/5
N2 - Two sulfated diterpene glycosides featuring a highly substituted and sterically encumbered cyclopropane ring have been isolated from the marine red alga Peyssonnelia sp. Combination of a wide array of 2D NMR spectroscopic experiments, in a systematic structure elucidation workflow, revealed that peyssonnosides A-B (1-2) represent a new class of diterpene glycosides with a tetracyclo [7.5.0.01,10.05,9] tetradecane architecture. A salient feature of this workflow is the unique application of quantitative interproton distances obtained from the rotating frame Overhauser effect spectroscopy (ROESY) NMR experiment, wherein the β-d-glucose moiety of 1 was used as an internal probe to unequivocally determine the absolute configuration, which was also supported by optical rotatory dispersion (ORD). Peyssonnoside A (1) exhibited promising activity against liver stage Plasmodium berghei and moderate antimethicillin-resistant Staphylococcus aureus (MRSA) activity, with no cytotoxicity against human keratinocytes. Additionally, 1 showed strong growth inhibition of the marine fungus Dendryphiella salina indicating an antifungal ecological role in its natural environment. The high natural abundance and novel carbon skeleton of 1 suggests a rare terpene cyclase machinery, exemplifying the chemical diversity in this phylogenetically distinct marine red alga.
AB - Two sulfated diterpene glycosides featuring a highly substituted and sterically encumbered cyclopropane ring have been isolated from the marine red alga Peyssonnelia sp. Combination of a wide array of 2D NMR spectroscopic experiments, in a systematic structure elucidation workflow, revealed that peyssonnosides A-B (1-2) represent a new class of diterpene glycosides with a tetracyclo [7.5.0.01,10.05,9] tetradecane architecture. A salient feature of this workflow is the unique application of quantitative interproton distances obtained from the rotating frame Overhauser effect spectroscopy (ROESY) NMR experiment, wherein the β-d-glucose moiety of 1 was used as an internal probe to unequivocally determine the absolute configuration, which was also supported by optical rotatory dispersion (ORD). Peyssonnoside A (1) exhibited promising activity against liver stage Plasmodium berghei and moderate antimethicillin-resistant Staphylococcus aureus (MRSA) activity, with no cytotoxicity against human keratinocytes. Additionally, 1 showed strong growth inhibition of the marine fungus Dendryphiella salina indicating an antifungal ecological role in its natural environment. The high natural abundance and novel carbon skeleton of 1 suggests a rare terpene cyclase machinery, exemplifying the chemical diversity in this phylogenetically distinct marine red alga.
UR - http://www.scopus.com/inward/record.url?scp=85068027334&partnerID=8YFLogxK
U2 - 10.1021/acs.joc.9b00884
DO - 10.1021/acs.joc.9b00884
M3 - Article
C2 - 31244158
AN - SCOPUS:85068027334
SN - 0022-3263
VL - 84
SP - 8531
EP - 8541
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 13
ER -