Coumestans

The three main classes of phytoestrogens (and common food sources) are isoflavones (soybeans), lignans (cereals and oilseeds such as flaxseed), and coumestans (alfalfa sprouts). The biologic potency of phytoestrogens varies and is less than that of synthetic estrogen. 

Estrogenic Glycosides (Isoflavones, Coumestans) Coumarin Glycosides Goitrogenic Glycosides Other Glycosides... 

Wagner H, Geyer B, Yoshinobu K, Govind SR. (1986) Coumestans as the main active principles of the liver drugs Eclipta alba and Wedelia calendu-lacea. Planta Med 5 370-372. 

During the synthesis of the natural and biologically active natural products, Stemo-furan A (139), Eupomatenoid b (140) and Coumestan (141), the [3,3]-sigmatropic rearrangements of a hydroxylamine were used. 

Kishore, P.H. et al., A new coumestan from Tephrosia calophylla. Chemical Pharmaceutical Bulletin, 51, 194, 2003. 

Benzo[i>]furans have also been prepared by a photocyclization of styrylfurans <99AG2753>. The first direct transformation of 2,2 -dihydroxychalcones into coumestans was reported. Thus, treatment of 29 with T1(N03)3 in methanol and subsequently with methanol/HQ in the presence of oxygen yields 30 <99T861>. 

The formation of the chromene caibamate 21 from resorcinol dicarbamate involves directed ortho metallation and an intramolecular 0- 0 carbamoyl transfer. Further manipulation utilising directed metallation and transition metal catalysed reactions allows the synthesis of plicadin, a naturally occurring coumestan <99AG(E)1435>. 

Coumestans,21 although they have a fused benzofuran ring, will be surveyed as being 8-lactones of 2-(2-hydroxyphenyl)-3-benzofuran carboxylic acids [coumestrol (4)22 is the 8-lactone of 2-(2,4-dihydroxy-phenyl)-6-hydroxy-3-benzofurancarboxylic acid]. The synthesis of some rotenoids 23 from benzofuran derivatives will also be reviewed, but dibenzofuran derivatives, such as usnic acid and its derivatives, will not be treated. 

An important extension of this method has made it possible to synthesize polycyclic benzofurans under the influence of various demethylating and dehydrating media.335 For such ring closures, pyridine hydrochloride is especially suitable thus coumestan has been synthesized from 4-hydroxy-3-(2-methoxyphenyl)coumarin.8 4,7-Di hydroxy-3-(2,4-dimethoxyphenyl)coumarin gives coumestol with aniline hydrochloride 336 other polymethoxycoumestans have been obtained with pyridine hydrochloride or with HBr (or HI) and acetic acid.337-339... 

Table 6 Occurrence of Pterocarpans and Coumestans (Selected Examples)"...

The first example of a natural coumestan, wedelolactone (227), was isolated by Govin-dachari and coworkers (57JCS548) from the leaves of Wedelia calendulacea. Since then a number of additional compounds of this type have been isolated. Selected examples are given in Scheme 43. 

A very simple synthesis of coumestrol (228) has been described by Kappe and coworkers (Scheme 46) (74ZN(B)292). It is based upon dehydrogenation of 4-hydroxy-3-phenyl-coumarins to coumestans (720PP233). A number of 2 -hydroxy 3-phenylcoumarins were oxidized with lead tetraacetate to the corresponding coumestans 3-(l-acetoxy-4-methoxy-2-oxo-3,5-cyclohexadienyl)coumarins were obtained as by-products (76BCJ1955). Coumes-tan itself (226) has been obtained by photolysis of the phenol ether (232), which is in turn available from 4-hydroxycoumarin (229) and (diacetoxyiodo)benzene (Scheme 47) (78CB3857) via an iodonium ylide (231). 

Another recent synthesis (76JHC909) consists of the Michael addition of an ethyl o-methoxybenzoylacetate to p-benzoquinone in the presence of zinc chloride and ethanol. Subsequent treatment of the resulting benzofuran with pyridinium chloride at 190-195 °C affords coumestans (Scheme 50). 

Another synthesis of pterocarpans starts from the coumestan system. LAH treatment results in reductive cleavage of the a-pyrone ring (Scheme 52). Benzofuran derivative (242) is thermally cyclized to (243) (64JCS4212 see also 78IJC(B)372), which may also be formed... 

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