
Coumarin (1,2-Benzopyrone) 
A bacterium isolated from soil metabolized coumarin to L-tyrosine in 
the culture medium (865, 866). In other studies, coumarin was converted 
to 7-hydroxycoumarin by Penicillium (103). Additional studies have indicated 
that a-coumaric acid and melilotic acid were intermediates in the degrada- 
tion of coumarin. When coumarin (I) was used as a substrate for Aspergillus 
niger, large amounts of melilotic acid (XX) were isolated. Small amounts 
of o-coumaric acid (XIV) and traces of 4-hydroxycoumarin (V) and catechol 
were also detected (129). 
A similar pathway in animals was suggested by experiments with rats 
(140) and rabbits (140, 515, 516, 965). Urine from rabbits administered 
coumarin (I) was collected and examined for coumarin metabolites. 3-Hydroxy- 
coumarin (II), 7-hydroxycoumarin (III), both free and as glucuronate 
conjugates and sulfate, and a trace of 8-hydroxycoumarin (XXIII) were 
detected. A small amount of o-coumaric acid (XIV) was detected in the free 
form and as the glucuronide. o-Coumaric acid was partially reduced, forming 
melilotic acid (XX), which cyclized to form dihydrocoumarin (XXII). Traces 
of o-coumaroylglycine (XIX) formed from o-coumaric acid (515, 965). When 
o-coumaric acid was administered to rabbits, melilotoylglycine (XXI), 
o-coumaroylglycine (XIX), umbelliferone (VIII), and 4-hydroxycoumarin (V) 
were detected in the urine (516). In other studies, o-hydroxyphenylhydracrylic 
acid (XV) o-hydroxyphenylacetic acid (XVII), and o-hydroxyphenyllactic acid 
(XVI) were also detected. Similar findings were obtained with rats (140). 
In addition to the 3-, 7-, and 8-hydroxycoumarins, which are excreted in 
conjugation, the ferret, guinea pig and mouse also excreted 5=hydroxycoumarin 
(XI) (965). 
Metabolism of coumarin by liver microsomes of rats, guinea pigs, and 
rabbits was also studied. TLC, UV, and I.R. were used to identify metabo- 
lites: 3-HO coumarin (II), o-HO-phenyllactate (XVI), o-HO-phenylpyruvate 
(XVIII), and o-HO-phenylacetate (XVII) (454, 782). 
In sweet clover, coumarin is rapidly converted to melilotic acid and 
its glucoside (832). It was postulated that coumarin was reduced to dihydro- 
coumarin and the pyrone ring was then opened to form melilotic acid. An 
enzyme was subsequently partially purified from sweet clover which catalyzed 
this ring opening (833). Exogenous coumarin was metabolized by lettuce seeds 
and seedlings. No metabolites were identified (1313). 
In man, 7-hydroxycoumarin (III) (80%) and o-hydroxyphenylacetic acid 
(XVII) (6%) were found after coumarin ingestion (1789). 
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