Coumarins, 8-prenylated

The furanocoumarins xanthotoxin (77) and isopimpinellim (78) from roots of A. acutiloba displayed significant AChE inhibitory activity with IC50 values of 0.58 xM and 0.32 xM respectively." Prenylated coumarins itom. Angelica spp. had only weak activity, with decursinol (79) giving the highest activity (IC50 value 28 xM)." ... 

Rumbero, A., Arriaga-Giner, F.J., and Wollenweber, E., A new ox5 prenyl coumarin and highly methylated flavones from the exudate of Ozothamnus lycopodioides (Asteraceae), Z. Naturforsch., 55c, 1, 2000. 

The major types of bioactive constituents reported from Broussonetia papyrifera are the prenylated flavonoids, which include compounds of the diphenylpropane, chalcone, flavan, flavanone, flavone, flavonol, and aurone classes (Table 2), Fig. (7). An early study on B. papyrifera resulted in the isolation of two diphenylpropanes, broussonins A (29) and B (30), and a coumarin, marmesin (52), with antifungal activity [39]. Also, a diprenylated diphenylpropane derivative, kazinol F (31) [40], was reported as an antioxidant and tyrosinase inhibitory constituent [34]. 

A number of natural flavonoids, coumarins and chromones have a prenyl (3-methylbut-2-enyl) side chain which is capable of cyclization on to an oxygen atom to form a pyran ring (77HC(31)633). Prenylation is effected by reaction with either 3-methylbut-2-enyl (prenyl) bromide or 2-methylbut-3-en-2-ol in the presence of a base or a Lewis acid. When this reaction is applied to flavonoids, the prenyl group has a choice of two benzene rings and... 

The phenolics include anthocyanins, anthraquinones, benzofurans, chromones, chromenes, coumarins, flavonoids, isoflavonoids, lignans, phenolic acids, phenylpropanoids, quinones, stilbenes and xanthones. Some phenolics can be very complex in structure through additional substitution or polymerization of simpler entities. Thus xanthones can be prenylated and flavonoids, lignans and other phenolics can be glycosylated. Condensed tannins involve the polymerization of procyaninidin or prodelphinidin monomers and hydrolysable tannins involve gallic acid residues esterified with monosaccharides. As detailed in this review, representatives of some major classes of plant-derived phenolics are potent protein kinase inhibitors. 

Preethulia coumarin 253 (Scheme 12.36) represents a naturally occurring analogue of ethuliacoumarin, a prenylated polyketide. 

This article is a summary of our recent extensive study of tumor specificity (TS) and the type of cell death induced by N-containing heterocycles such as 4-trifluoromethylimidazole [22] and phenoxazine derivatives [23], by O-containing heterocycles such as 3-formylchromone [24] and coumarin derivatives [25,26], and by other compounds such as vitamin K2 and prenyl-alcohols [27]. 

Glycycoumarin (prenylated coumarin) Glycyrrhiza uralensis (liquorice) [root, rhizome] (Fabaceae) cAMP PDE (7)... 

The Pd-catalysed Miyaura-Suzuki coupling of aryltrifluoroborates with 4-tosyloxycoumarins in aqueous conditions offers an attractive route to 4-arylcoumarins <06TL1525> and 4-hydroxycoumarins have been converted into a mixture of predominantly thiopyrano[5, 4 3,4]- pyrano[5,6-c]coumarins and [6,5-c]chromones in a one-pot tandem Knoevenagel - HDA sequence with an S-prenylated 1-phenyl-lff-pyrazole-4-carbaldehyde <06TL2265>. The benzopyrano[4,3-c]benzopyranone system can be obtained from 3-aryl-4-methylcoumarins by deprotonation of the methyl function and subsequent elaboration <06TL5909>. 

Umbelliferone is the pivotal metabolite in the pathways to substituted coumarins and furano- or pyranocoumarins. Its 7-0-methylation to herniarin (Fig. 4.3) or 0-prenylation and C-alkylation reactions are often observed in coumarin-producing higher plants where the prenylation at C-6 or C-8 mark the entry to the routes branching linear from angular furano- and pyranocoumarins (Fig. 4.5). In Ruta graveolens and Ammi rmjus, the prenylation reactions are catalysed by particulate enzymes (Hamerski et at, 1990), and... 

The simple coumarin nucleus (Fig 7.3), which is derived by lactone formation of an ortho-hydroxy-czs cinnamic acid, is a common metabolite in higher plants and is often found in glycosidic form. Coumarins are common in Api-aceae, in certain genera of Fabaceae (e.g. Dipteryx odorata, Melilotus officinalis), Poaceae (e.g. Anthoxanthum odoratum) and Rubiaceae (e.g. Galium odoratum). However, proliferation of coumarins to the status of major chemical markers occurs in only a few cases, most notably, but not exclusively, in the Api-aceae (subfamily Apioideae) and in the Rutaceae (Gray and Waterman, 1978 Murray et al., 1982). In these cases, the coumarin nucleus has almost invariably been embellished by the addition of a prenyl unit leading to furocoumarin (Fig 7.3) and pyranocoumarin structures. 

Hydroxylation of p-coumaric acid, followed by photocatalyzed isomerization of the double bond and lactonization, affords 7-hydroxy coumarin (umbel-liferone). Prenylation at the 6-position, epoxidation, cyclization, and a retro-aldol reaction afford the furanocoumarins (Fig. 14) some (psoralen, bergapten)... 

Other antimicrobial phenolic compounds from the Anthemideae tribe are coumarins, which are derivatives of benzo-a-pyrone. Feresin et al. [199] isolated eight / -coumaric acid derivatives from the Argentinian medicinal plant Baccharis grisebachii. Two of them, 3-prenyl-/ -coumaric acid, Fig. (38) and 3,5-diprenyl-p-coumaric acid were active towards Epidermophyton floccosum and Trichophyton rubrum, with MIC values of 50 and 100-125 ig/ml, respectively. 

A related domino process was used for the synthesis of coumarin derivatives that contain sugar-fused moieties. In the presence of NaOAc and HOAc, the reaction of coumarin 159 with prenylated sugar aldehyde 160 produced 161 in 82% yield (equation (5)) (04TL3493). A variety of 1,3-dicarbonyl compounds also participated in the reaction and provided tandem condensation/cycloaddition products in good yields (70-80%). 

Photolysis of coumarin-3-carbonylazides gives nitrenes in the triplet state, and these have been trapped by hydrocarbons and by aniline. Prenyl ethers of 3-hydroxycoumarins undergo an abnormal Claisen rearrangement and give the 4-allyUc compound (193), but, in the presence of an 8-methoxy-group, the side-chain is further rearranged as in (192). ... 

A variety of 2-substituted 2//-chromenes can be obtained from the facile reaction of 2-hydroxybenzaldehydes with vinylboronic acids in ionic liquid solvents <04SL2194>. In a one-pot sequence also in an ionic liquid, a Knoevenagel condensation between O-prenylated salicylaldehydes and 4-hydroxycoumarins is followed by an intramolecular hDA reaction to yield ci5-fused chromano[4, 3 4,5]pyrano[3,2-c]coumarins e.g. 20 small amounts of the corresponding chromone are also formed <04S1783>. In like manner, cii-fused furopyranopyran derivatives have been obtained from sugar aldehydes <04TL3493>. 

Natural Prenyl Coumarins, Chromones and related Structures... 

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