Coumarin derivatives
{{Short description|Organic compounds derived from coumarin}}
{{Redirect|Coumarins|the class of anticoagulants and rodenticides specifically|4-Hydroxycoumarins|the parent compound|Coumarin}}
Coumarin derivatives are derivatives of coumarin and are considered phenylpropanoids.{{cite journal |last1=Jacobowitz |first1=Joseph R. |last2=Weng |first2=Jing-Ke |date=2020-04-29 |title=Exploring Uncharted Territories of Plant Specialized Metabolism in the Postgenomic Era |journal=Annual Review of Plant Biology |publisher=Annual Reviews |volume=71 |issue=1 |pages=631–658 |doi=10.1146/annurev-arplant-081519-035634 |issn=1543-5008 |pmid=32176525 |s2cid=212740956}} Among the most important derivatives are the 4-hydroxycoumarins, which exhibit anticoagulant properties, a characteristic not present for coumarin itself.
Some naturally occurring coumarin derivatives include umbelliferone (7-hydroxycoumarin), aesculetin (6,7-dihydroxycoumarin), herniarin (7-methoxycoumarin), psoralen and imperatorin.
4-Phenylcoumarin is the backbone of the neoflavones, a type of neoflavonoids.
Coumarin pyrazole hybrids have been synthesized from hydrazones, carbazones and thiocarbazones via Vilsmeier Haack formylation reaction.
Compounds derived from coumarin are also called coumarins or coumarinoids; this family includes:
- brodifacoum{{cite web |author=International Programme on Chemical Safety |title=Brodifacoum (pesticide data sheet) |url=http://www.inchem.org/documents/pds/pds/pest57_e.htm |url-status=dead |archive-url=https://web.archive.org/web/20061209133155/http://inchem.org/documents/pds/pds/pest57_e.htm |archive-date=2006-12-09 |access-date=2006-12-14}}{{cite journal |last1=Laposata |first1=M |last2=Van Cott |first2=E. M. |last3=Lev |first3=M. H. |year=2007 |title=Case 1-2007—A 40-Year-Old Woman with Epistaxis, Hematemesis, and Altered Mental Status |journal=New England Journal of Medicine |volume=356 |issue=2 |pages=174–82 |doi=10.1056/NEJMcpc069032 |pmid=17215536}}
- bromadiolone{{cite web |author=International Programme on Chemical Safety |title=Bromadiolone (pesticide data sheet) |url=http://www.inchem.org/documents/pds/pds/pest88_e.htm |url-status=dead |archive-url=https://web.archive.org/web/20061221043656/http://www.inchem.org/documents/pds/pds/pest88_e.htm |archive-date=2006-12-21 |access-date=2006-12-14}}
- difenacoum{{cite web |author=International Programme on Chemical Safety |title=Difenacoum (health and safety guide) |url=http://www.inchem.org/documents/hsg/hsg/hsg095.htm |access-date=2006-12-14}}
- auraptene
- ensaculin
- phenprocoumon (Marcoumar)
- PSB-SB-487
- PSB-SB-1202
- scopoletin can be isolated from the bark of Shorea pinanga{{cite journal |last1=Syah |first1=Y. M. |display-authors=etal |year=2009 |title=A modified oligostilbenoid, diptoindonesin C, from Shorea pinanga Scheff |journal=Natural Product Research |volume=23 |issue=7 |pages=591–594 |doi=10.1080/14786410600761235 |pmid=19401910 |s2cid=20216115}}
- warfarin (Coumadin)
Coumarin is transformed into the natural anticoagulant dicoumarol by a number of species of fungi.{{cite journal |last1=Venugopala |first1=K. N. |last2=Rashmi |first2=V |last3=Odhav |first3=B |year=2013 |title=Review on Natural Coumarin Lead Compounds for Their Pharmacological Activity |journal=BioMed Research International |volume=2013 |pages=1–14 |doi=10.1155/2013/963248 |pmc=3622347 |pmid=23586066 |doi-access=free}} This occurs as the result of the production of 4-hydroxycoumarin, then further (in the presence of naturally occurring formaldehyde) into the actual anticoagulant dicoumarol, a fermentation product and mycotoxin. Dicoumarol was responsible for the bleeding disease known historically as "sweet clover disease" in cattle eating moldy sweet clover silage.{{cite journal |last1=Bye |first1=A. |last2=King |first2=H. K. |year=1970 |title=The biosynthesis of 4-hydroxycoumarin and dicoumarol by Aspergillus fumigatus Fresenius |journal=Biochemical Journal |volume=117 |issue=2 |pages=237–45 |doi=10.1042/bj1170237 |pmc=1178855 |pmid=4192639}} In basic research, preliminary evidence exists for coumarin having various biological activities, including anti-inflammatory, anti-tumor, antibacterial, and antifungal properties, among others.
Uses
=Medicine=
Warfarin – a coumarin – with brand name, Coumadin, is a prescription drug used as an anticoagulant to inhibit formation of blood clots, and so is a therapy for deep vein thrombosis and pulmonary embolism.{{cite web |url=https://pubchem.ncbi.nlm.nih.gov/compound/323 |title=Coumarin |date=4 April 2019 |publisher=PubChem, National Library of Medicine, US National Institutes of Health |access-date=13 April 2019}}{{cite web |url=https://www.drugs.com/drug-class/coumarins-and-indandiones.html |title= Coumarins and indandiones |publisher=Drugs.com |date=2016 |access-date=24 December 2016}}{{cite web |title=Warfarin |url=https://www.drugs.com/ppa/warfarin.html |publisher=Drugs.com |access-date=13 April 2019 |date=7 March 2019}} It may be used to prevent recurrent blood clot formation from atrial fibrillation, thrombotic stroke, and transient ischemic attacks.
Coumarins have shown some evidence of biological activity and have limited approval for few medical uses as pharmaceuticals, such as in the treatment of lymphedema.{{cite journal|last1=Farinola|first1=N. |first2=N. |last2=Piller|journal=Lymphatic Research and Biology|date=June 1, 2005|volume=3|issue=2|pages=81–86|doi=10.1089/lrb.2005.3.81|title=Pharmacogenomics: Its role in re-establishing coumarin as treatment for lymphedema|pmid=16000056}} Both coumarin and 1,3-indandione derivatives produce a uricosuric effect, presumably by interfering with the renal tubular reabsorption of urate.{{Cite journal| doi = 10.1111/j.0954-6820.1964.tb00594.x| issn = 0954-6820| volume = 175| issue = 4| pages = 461–468| last = Christensen| first = Flemming| title = Uricosuric Effect of Dicoumarol| journal = Acta Medica Scandinavica| date = 1964-01-12| pmid = 14149651}}
=Laser dyes=
Coumarin dyes are extensively used as gain media in blue-green tunable organic dye lasers.{{cite book|editor1-link=F. P. Schäfer|editor1-last=Schäfer|editor1-first=F. P.|title=Dye Lasers|edition=3rd|location=Berlin|publisher=Springer-Verlag|date=1990}}{{ISBN missing}}{{cite book|editor1-link=F. J. Duarte|editor1-last=Duarte|editor1-first=F. J.|editor2-first=L. W.|editor2-last=Hillman|title=Dye Laser Principles|location=New York|publisher=Academic|date=1990}}{{ISBN missing}}{{cite book|last=Duarte|first=F. J.|title=Tunable Laser Optics|location=New York|publisher=Elsevier-Academic|date=2003|chapter=Appendix of Laser Dyes}}{{ISBN missing}} Among the various coumarin laser dyes are coumarins 480, 490, 504, 521, 504T, and 521T. Coumarin tetramethyl laser dyes offer wide tunability and high laser gain,{{cite journal|last1=Chen |first1=C. H. |last2=Fox |first2=J. L. |last3=Duarte |first3=F. J. |title=Lasing characteristics of new-coumarin-analog dyes: broadband and narrow-linewidth performance |journal=Appl. Opt. |volume=27 |issue=3 |pages=443–445 |date=1988 |doi=10.1364/ao.27.000443|pmid=20523615 |bibcode=1988ApOpt..27..443C }}{{cite journal|last1=Duarte |first1=F. J. |last2=Liao |first2=L. S. |last3=Vaeth |first3=K. M. |last4=Miller |first4=A. M. |title=Widely tunable laser emission using the coumarin 545 tetramethyl dye as gain medium |journal=J. Opt. A |volume=8 |issue=2 |pages=172–174 |date=2006 |doi=10.1088/1464-4258/8/2/010|bibcode=2006JOptA...8..172D }} and they are also used as active medium in coherent OLED emitters.{{cite journal|last1=Duarte |first1=F. J. |last2=Liao |first2=L. S. |last3=Vaeth |first3=K. M. |title=Coherence characteristics of electrically excited tandem organic light-emitting diodes |journal=Opt. Lett. |volume=30 |issue=22 |pages=3072–3074 |date=2005 |doi=10.1364/ol.30.003072 |pmid=16315725|bibcode=2005OptL...30.3072D }} and as a sensitizer in older photovoltaic technologies.{{cite patent|country=US|number=4175982|inventor=Loutfy et al.|gdate=Nov. 27, 1978|assign1=Xerox Corp}}