Isoflav-3-enes

The estrogenic properties of isoflav-3-enes are well known and consequently, several derivatives of these chromene heterocycles have been the target of medicinal chemists. Varma and coworkers uncovered a useful enamine-mediated pathway to this class of compounds [142-144], Now the group has discovered a facile and general method for the MW-expedited synthesis of isoflav-3-enes substituted with basic moieties at the 2-position (Scheme 6.42) [145], These promising results are especially appealing in view of the convergent one-pot approach to 2-substituted isoflav-3-enes... 

Scheme 6.42 One-pot synthesis of 2-substituted isoflav-3-enes from in situ- generated enamines.

Yenesew, A. et al.. Three isoflav-3-enes and a 2-arylbenzofuran from the root bark of Erythrina burttii, Phytochemistry, 59, 337, 2002. 

Keywords phenyl acetaldehyde, cyclic secondary amine, salicylaldehyde, micro-wave irradiation, 2-amino-isoflav-3-ene... 

Scheme 14 Synthesis of 2-amino substituted isoflav-3-enes from enamines [69]...

The solvent-free MW-assisted synthesis of 2-amino-substituted isoflav-3-enes has been reported it ean be aehieved in one pot via the in situ generation of enamines and their subsequent reaetions with salicylaldehydes (Scheme 8.22). This environmentally friendly procedure does not require azeotropic removal of water using large excess of aromatic hydrocarbon solvents for the generation of enamines. 

Scheme 8.22 MW-assisted solvent-free synthesis of substituted isoflav-3-enes.

The mixture of compounds contained in the crude extract were separated by chromatography on silica gel using various organic solvents. This process led to the isolation of three chalcones, 11 prenylated flavanones, three pterocarpanoids and one isoflav-3-ene (Figure 3). While the details of the characterization of these compounds have been reported elsewhere, it is worth pointing out that in the bioassay assessment referred to above, they had reasonable LC50 values (Table 4). They had antimalarial activities comparable to those of the crude extracts and should be the principles responsible for the activity. 

It has already been noted that there is a considerable structural variation among isoflavonoids and at least three other structural types are represented in the genus Cicer. Note that the numbering systems for these variants differ from each other. Isoflav-3-enes conform to the usual flavonoids numbering system but coumestanes and arylbenzofurans are different. 

The arylbenzofurans are marginally more common than isoflav-3-enes but they still constitute an unusual and infrequently occurring group of isoflavonoids. Cicerfuran (2-(2 -methylenedioxyphenyl)-6-... 

Bearing these taxonomic conclusions in mind, an overview of likely biosynthetic relationships between the isoflavonoids discussed in this chapter was proposed [6] and is represented in Fig. (4). This emphasises those compounds whose occurrence is restricted to the 3 species in the proposed series Pinnatifida (C. bijugum, C. judaicum and C. pinnatifidum) and attempted to address the biosynthesis of these compounds, most notably arybenzofurans which are still missing from the latest versions of the isoflavonoid biosynthesis schemes because of the lack of persuasive biogenetic evidence. A 2 -hydroxyisoflavanol, the immediate precursor of isoflav-3-enes and pterocarpans, is shown as the first intermediate. Its... 

Most of the reported metabolites from Erythrina belong to the general class of isoflavonoids, whose biogenetic relationship is shown in Fig. (2). Under lhis general class are compounds reported to fall into the following classes isoflavones (biggest), pterocarpans, isoflavanones, isoflavans, isoflav-3-enes, coumastans and 3-phenylcoumarins, and phenoxychromones. 

Bronstedt adds were used to catalyze the MW-accelerated multicomponent synthesis of substituted isoflav-3-enes 52 (Scheme 17.38) [96]. 

---