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United States Department of Agriculture

Agricultural Research Service

Research Project: DISCOVERY AND DEVELOPMENT OF NATURAL PRODUCTS FOR PHARMACEUTICAL AND AGROCHEMICAL APPLICATIONS

Location: Natural Products Utilization Research

Title: UPLC-MS-ELSD-PDA as a powerful dereplication tool to facilitate compound identification from small molecule natural product libraries

Author
item Yang, Jin
item Liang, Qian
item Wang, Mei
item Jeffries, Cynthia
item Smithson, David
item Tu, Ying
item Boulos, Nidal
item Jacob, Melissa
item Shelat, Anang
item Wu, Yunshan
item Gilbertson, Richard
item Avery, Mitchell
item Khan, Ikhlas
item Walker, Larry
item Guy, R. Kiplin
item Li, Xing-cong

Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/14/2014
Publication Date: 3/11/2014
Citation: Yang, J., Liang, Q., Wang, M., Jeffries, C., Smithson, D., Tu, Y., Boulos, N., Jacob, M.R., Shelat, A.A., Wu, Y., Gilbertson, R., Avery, M.A., Khan, I.A., Walker, L.A., Guy, R., Li, X. 2014. UPLC-MS-ELSD-PDA as a powerful dereplication tool to facilitate compound identification from small molecule natural product libraries. Journal of Natural Products. 77:902-909.

Interpretive Summary: This manuscript describes UPLC-MS-ELSD-PDA as a powerful tool that can be used for selection and prioritization of hits in a natural product discovery program. Examples are provided to show how this technique was utilized to guide rapid and efficient dereplication and subsequent structure determination.

Technical Abstract: Generation of natural product libraries containing column fractions, each with only a few small molecules, by a high throughput, automated fractionation system has made it possible to implement an improved dereplication strategy for selection and prioritization of hits in a natural product discovery program. Analysis of databased UPLC-MS-ELSD-PDA data of three hits from a biological screen employing the ependymoma cell line EphB2-EPD generated information on possible structures of active compounds. The procedure allowed rapid identification of known compounds and guided the isolation of unknown compounds of interest. Three known flavanonetype compounds homoeriodictyol (1), hesperetin (2) and sterubin (3) were identified in the hit fraction derived from the leaves of Eriodictyon angustifolia. The lignan compound deoxypodophyllotoxin (8) was confirmed to be an active constituent in two hit fractions derived from the bark and leaves of Thuja occidentalis. In addition, two new but inactive labdane-type diterpenoids with an uncommon triol side chain were also identified as coexisting with deoxypodophyllotoxin in the hit fraction from the bark of T. occidentalis. Both diterpenoids were isolated in acetylated form and their structures determined to be 14S,15-diacetoxy-13Rhydroxy-labd-8(17)-en-19-oic acid (9) and 14R,15-diacetoxy-13S-hydroxy-labd-8(17)-en-19-oic acid (10) by spectroscopic methods and X-ray crystallography. This work demonstrates that the UPLC-MS-ELSD-PDA database produced during fractionation is a powerful dereplication tool that facilitates compound identification from chromatographically tractable small molecule natural product libraries.

Last Modified: 10/17/2017
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