Coumarin formation

Kojic acid — see also Pyran-4-one, 5-hydroxy-2-hydroxymethyl-, 3, 611 acylation, 3, 697 application, 3, 880 occurrence, 3, 692 reactions, 3, 714, 715 with amines, 3, 700 with phenylhydrazine, 3, 700 synthesis, 3, 810 Kokusagine occurrence, 4, 989 Kokusaginine occurrence, 4, 989 synthesis, 4, 990 Koopmans theorem, 2, 135 Kostanecki-Robinson reaction chromone and coumarin formation in, 3, 819-821 mechanism, 3, 820 flavones, 3, 819... 

Coumarin formation proceeds via an intramolecular attack by enol ester 9 on the ketone to give 10. Dehydration of 10 then affords coumarin 11. It has been observed that coumarins are favored when higher order homologs of acetic anhydride and their corresponding salts such as propionic anhydride/sodium propionate and butyric anhydride/ sodium butyrate are used. 

Chen, H. and Walsh, C.T. (2001) Coumarin formation in novobiocin biosynthesis beta-hydroxylation of the aminoacyl enzyme tyrosyl-S-NovH by a cytochrome P450 Novi. Chemistry Biology, 8, 301-312. 

Hydroarylation of alkynoates with phenols is applied to the synthesis of calanolides A 17 and B 18, which are active against AZT-resistant strains of HIV-1.163 The key step is the palladium-catalyzed coumarin formation reaction, as shown in Scheme 18. 

Substituents in the pyranone ring are derived from the dicarbonyl component and hence variation in the nature of 3- and 4-substituents is relatively easy. Thus, ethyl benzoylacetate gives 4-phenylcoumarins as for instance in a synthesis of dalbergin (357) (76T2407, 8iiJC(B)9l8) and use of ethyl trifluoroacetoacetate leads to 4-trifluoromethylcoumarins. A study of the reaction of the latter with 3-aminophenol identified the optimum conditions for coumarin formation, but noted the simultaneous formation of the two quinoline derivatives (358) and (359) (80JOC2283). 

When applied to an o-hydroxybenzaldehyde, initial acylation of the hydroxy group occurs. Subsequently, two modes of coumarin formation have been postulated involving either an intramolecular or an intermolecular condensation. The available evidence suggests that both processes may occur (53JCS3435). 

The prenylated benzoic acid and the coumarin ring are derived from L-tyrosine. Walsh et al. proposed a biosynthetic pathway for coumarin formation in which NovH, a didomainal enzyme containing an adenylation (A) domain and a thiolation (T) domain, catalyzes L-tyrosyl-AMP formation. The A domain of NovH selects and... 

The intermediacy of o-hydroxycinnamic acid esters (5) in the Pechmann condensation was first proposed by Pechmann in 1884. In 1932, Robertson and co-workers provided support for this proposal through their examination of the reactions of w-methylanisole and dimethylresorcinol with ethyl acetoacetate under the conditions of the Pechmann condensation. Allowing these anisoles to stand with ethyl acetoacetate in sulfuric acid resulted in the formation of 4,7-dimethylcoumarin and 7-methoxy-4-methylcoumarin, respectively. 3 -(2-Methoxy-4-methylphenyl)-2-butenoic acid could likewise be converted to 4,7-dimethylcoumarin under similar conditions. These observations revealed cinnamate intermediates such as 5 to be viable intermediates in the Pechmann condensation and demonstrated that the formation of aryl acetoacetate intermediates such as 4 is not required for coumarin formation. 

Coumarins, formation from condensation of ethyl pyridyl-acetates with o-hydroxy-aromatic aldehydes, 345 Pechmann condensation of ethyl nicotinoylacetate with... 

Zagorevskii [162] has shown that in the coumarin formation, the trichloro compound probably isomerises to (93) which then reacts with the alcohol (Figure 2.13). 

A disadvantage of the von Pechmann synthesis is the lack of regioselectivity in coumarin formation with unsymmetrically substituted phenolic substrates. This is avoided by an alternative protocol [37], in which ortho-metalated phenolic ethers 16 are added to alkoxymethylene malonates as primary step ... 

Figure 1.36 (a) Ir-catalyzed isocoumarin formation [86] and (b) Rh-catalyzed phosphaiso-coumarin formation [87]. 

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