Coumarins 3.4- dihydrocoumarin derivatives

Rezayan, P. Azerang, S. Sardari, A. Sarvary, Chem. Biol. Drug Des. 2012, 80,929-936. Synthesis and biological evaluation of coumarin derivatives as inhibitors of mycobacterium bovis (BCG), (c) A. Shaabani, A. Sarvary, E. Soleimani, A. H. Rezayan, M. Heidary, Mo/. Divers. 2008,12,197-202. A novel method for the synthesis of snbstitnted 3,4-dihydro-coumarin derivatives via isocyanide-based three-component reaction, (d) A. Shaabani, E. Soleimani, A. H. Rezayan, A. Sarvary, H. R. Khavasi, Org. Lett. 2008, 10, 2581-2584. Novel isocyanide-based four-component reaction a facile synthesis of fuUy substituted 3,4-dihydrocoumarin derivatives. 

Ketones derived from pyrans are called pyranones (also commonly pyrones), and the parent compounds are pyran-2-one 17 and pyran-4-one 18. Trivial names are used for the related benzo analogs coumarin 19, isocoumarin 20, dihydrocoumarin 21, chromone 22, xanthone 23, and chromanone 24. 

Electrochemical reduction of coumarin [187] affords the meso and ( ) forms of a product hydrodimerized (at C-4) like many other a,)6-unsaturated acid derivatives. In the presence of tertiary amines, which are not destroyed during the process but catalyze the evolution of hydrogen, a transfer of hydrogen takes place from the amine radical to the coumarin radical with formation of 3,4-dihydrocoumarin. Asymmetric amines cause asymmetric induction during the reduction of 4-methylcoumarin, as in Chapter 26 [188]. 

Reduction of coumarins to the dihydro-derivatives has frequently been achieved, but a more efficient procedure has emerged from a new study of this conversion. The most effective method was catalytic reduction in ethanol at 150 °C and under a high pressure (1500 psi) of hydrogen of give mostly the 2-hydroxy-3-phenylbutanoate, which was readily cyclized with PPA to the dihydrocoumarin. Hydroboration of 3-arylcoumarins, followed by oxidation, gave isoflavanones the latter have been dehydrogenated (with DDQ) to isoflavones. A reaction of wide potential value is the selective hydrolysis by zinc and methanol of phenolic acetates in the presence of aUphatic acetate groups. 

About 80 lactones have been identified in tobacco smoke. These compounds, especially they-butyrolactones, andothers, have alkylating potential and some have been reported to be carcinogenic in laboratory animals [Lawley (6A12)]. [see also Appendix 2, pp. 387-394) in (1870)]. Quantitatively, about half the lactones in the smoke consist of y-butyrolactone [lARC (6A10)] (about 10 pg/cigarette) and its derivatives 5-valerolactone and some alkylated and unsaturated 5-valerolactones, as well as coumarin [see pp. 427-430 in Wynder and Hoffmann (4332)], 6-methylcoumarin, and 3,4-dihydrocoumarin have also been isolated [Schumacher et al. (3553)]. The occurrence of coumarin derivatives in smoke could be due to pyrolysis of polyphenols with a coumarin structure. .. or of plant extracts added to tobacco to enhance flavour [see pp. 427-430 in Wynder and Hoffmann (4332)]. Coumarin itself is carcinogenic to rats after oral administration [lARC (6A10)]. 

The metabolism of other closely related coumarin derivatives has also been investigated mainly in rabbits and rats by different authors [56, 57, 59, 68]. Different amounts of metabolites with intact ring systems or of open ring and other phenolic derivatives were identified when the biotransformation of 3,4-dihydrocoumarin [69], 4-methylcoumarin [70], 3,4-dihydro-6-methylcoumarin [71], and hydroxycoumarins [48, 53] were studied in rats [72] (Table 3.2). Like the major route of 7-hydroxylation of coumarin, dicoumarol (13) and tromexan (ethyl-bis-coumacetate) are also metabolised by hydroxylation in man, mostly in the 7-position (14) of one of the coumarin rings (Figure 3.4) [73, 74]. 

The intramolecular esters, the lactones, may be mentioned here. The antihelminthic agent santonin, for example, belongs to this class. A well known lactone is coumarin, the odour of which resembles dried woodruff and which is found in numerous essential oils, also as derivatives. SuND and Saccabdi [273] have succeeded in separating 5 cou-marins on silica gel G layers, using petroleum ether (50—75° C)-ethyl acetate (67 + 33) or n-hexane-ethyl acetate (72 + 29). The sequence found was coumarin, 6-methylcoumarm, dihydrocoumarin, 3-methylcoumarin, 3-ethylcoumarin. 

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