Synthesis and Biological Evaluation of 6-[(1R)-1-Hydroxyethyl]-2,4a(R),6(S),8a(R)-tetrahydropyrano-[3,2-b]-pyran-2-one and Structural Analogues of the Putative Structure of Diplopyrone
- Nicholas C. LazzaraNicholas C. LazzaraDepartment of Chemistry, Villanova University, Villanova, Pennsylvania 19085, United StatesMore by Nicholas C. Lazzara
- ,
- Robert J. RosanoRobert J. RosanoDepartment of Chemistry, Villanova University, Villanova, Pennsylvania 19085, United StatesMore by Robert J. Rosano
- ,
- Purav P. VagadiaPurav P. VagadiaDepartment of Chemistry, Villanova University, Villanova, Pennsylvania 19085, United StatesMore by Purav P. Vagadia
- ,
- Matthew T. GiovineMatthew T. GiovineDepartment of Chemistry, Villanova University, Villanova, Pennsylvania 19085, United StatesMore by Matthew T. Giovine
- ,
- Mark W. BezpalkoMark W. BezpalkoDepartment of Chemistry, Villanova University, Villanova, Pennsylvania 19085, United StatesMore by Mark W. Bezpalko
- ,
- Nicholas A. PiroNicholas A. PiroDepartment of Chemistry, Villanova University, Villanova, Pennsylvania 19085, United StatesMore by Nicholas A. Piro
- ,
- Wm. Scott KasselWm. Scott KasselDepartment of Chemistry, Villanova University, Villanova, Pennsylvania 19085, United StatesMore by Wm. Scott Kassel
- ,
- Walter J. BoykoWalter J. BoykoDepartment of Chemistry, Villanova University, Villanova, Pennsylvania 19085, United StatesMore by Walter J. Boyko
- ,
- Deanna L. ZubrisDeanna L. ZubrisDepartment of Chemistry, Villanova University, Villanova, Pennsylvania 19085, United StatesMore by Deanna L. Zubris
- ,
- Kevin K. SchraderKevin K. SchraderNatural Products Utilization Research Unit, Agricultural Research Service, U.S. Department of Agriculture, P.O. Box 1848, University, Mississippi 38677, United StatesMore by Kevin K. Schrader
- ,
- David E. WedgeDavid E. WedgeNatural Products Utilization Research Unit, Agricultural Research Service, U.S. Department of Agriculture, P.O. Box 1848, University, Mississippi 38677, United StatesMore by David E. Wedge
- ,
- Stephen O. DukeStephen O. DukeNatural Products Utilization Research Unit, Agricultural Research Service, U.S. Department of Agriculture, P.O. Box 1848, University, Mississippi 38677, United StatesMore by Stephen O. Duke
- , and
- Robert M. Giuliano*Robert M. Giuliano*E-mail: [email protected]Department of Chemistry, Villanova University, Villanova, Pennsylvania 19085, United StatesMore by Robert M. Giuliano
Abstract
The phytotoxin diplopyrone is considered to be the main phytotoxin in a fungus that is responsible for cork oak decline. A carbohydrate-based synthesis of the enantiomer of the structure proposed for diplopyrone has been developed from a commercially available derivative of d-galactose. Key steps in the synthesis are a highly stereoselective pyranose chain-extension based on methyltitanium, preparation of a vinyl glycoside via Isobe C-alkynylation-rearrangement/reduction, and RCM-based pyranopyran construction. Crystallographic and NMR analysis confirms an earlier report that the structure originally proposed for diplopyrone may require revision. Structural analogues were prepared for biological evaluation, the most promising being a pyranopyran nitrile synthesized from tri-O-acetyl-d-galactal by Ferrier cyanoglycosidation, Wittig chain extension, and lactonization. Biological assays revealed potent antibacterial activity for the nitrile analogue against common bacterial pathogens Edwardsiella ictaluri and Flavobacterium columnare that cause enteric septicemia (ESC) and columnaris disease, respectively, in catfish. The IC50 value of 0.002 against E. ictaluri indicates approximately 100 times greater potency than the antibiotic florfenicol used commercially for this disease. Phytotoxic activity for all three target compounds against duckweed was also observed. The antibiotic and phytotoxic activities of the new pyranopyrans synthesized in this study demonstrate the potential of such compounds as antibiotics and herbicides.
Cited By
This article is cited by 9 publications.
- Jack H. Roireau, Robert J. Rosano, Nicholas C. Lazzara, Thomas Chen, Joanna Bajsa-Hirschel, Kevin K. Schrader, Stephen O. Duke, Dennis Wykoff, Robert M. Giuliano. Synthesis of Pyranopyrans Related to Diplopyrone and Evaluation as Antibacterials and Herbicides. Journal of Agricultural and Food Chemistry 2020, 68
(37)
, 9906-9916. https://doi.org/10.1021/acs.jafc.0c02564
- Ariel M. Sarotti. In Silico Reassignment of (+)-Diplopyrone by NMR Calculations: Use of a DP4/J-DP4/DP4+/DIP Tandem to Revise Both Relative and Absolute Configuration. The Journal of Organic Chemistry 2020, 85
(17)
, 11566-11570. https://doi.org/10.1021/acs.joc.0c01563
- Philemon Ngoje, David Crich. Synthesis of Bradyrhizose from d-Glucose. Organic Letters 2020, 22
(2)
, 523-527. https://doi.org/10.1021/acs.orglett.9b04279
- Ryan D. Simard, Mathieu Joyal, Laura Gillard, Gianna Di Censo, Wael Maharsy, Janie Beauregard, Pina Colarusso, Kamala D. Patel, Michel Prévost, Mona Nemer, Yvan Guindon. Synthesis of Sialyl LewisX Glycomimetics Bearing a Bicyclic 3-O,4-C-Fused Galactopyranoside Scaffold. The Journal of Organic Chemistry 2019, 84
(11)
, 7372-7387. https://doi.org/10.1021/acs.joc.9b01075
- K. Fabitha, Anoop Kallingal, Natalia Maciejewska, C. G. Arya, Munugala Chandrakanth, Neethu Mariam Thomas, Yupeng Li, Ramesh Gondru, Manne Munikumar, Janardhan Banothu. Novel fused pyran derivatives induce apoptosis and target cell cycle progression in anticancer efficacy against multiple cell lines. New Journal of Chemistry 2024, 71 https://doi.org/10.1039/D4NJ00824C
- Ana Marta de Matos. Recent Advances in the Development and Synthesis of Carbohydrate‐Based Molecules with Promising Antibacterial Activity. European Journal of Organic Chemistry 2023, 26
(4)
https://doi.org/10.1002/ejoc.202200919
- Clementina M.M. Santos, Artur M.S. Silva. Six-membered ring systems: with O and/or S atoms. 2021, 501-563. https://doi.org/10.1016/B978-0-323-89812-6.00015-8
- Qingwei Lv, Caizhu Chang, Yong Li, Yuguo Du, Jun Liu. Stereoselective synthesis of (−)-protulactone A. Tetrahedron 2020, 76
(26)
, 131290. https://doi.org/10.1016/j.tet.2020.131290
- John Greene, Noa Kopplin, Jack Roireau, Mark Bezpalko, Scott Kassel, Michael W. Giuliano, Robert Giuliano. Synthesis and crystal structure of (2
S
,4a
R
,8a
R
)-6-oxo-2,4a,6,8a-tetrahydropyrano[3,2-
b
]pyran-2-carboxamide. Acta Crystallographica Section E Crystallographic Communications 2020, 76
(5)
, 761-764. https://doi.org/10.1107/S2056989020001292