Benzopyran scaffold

H-benzopyran core structure. This approach for the construction of the 2H-benzopyran scaffold was developed by Shigemasa [22]. However, the authors found that the reaction of the ethyl ester with the aldehyde was extremely slow under Shigemasa s conditions. 

A combinatorial natural-product-like and diversity-orientated library of 10 000 benzopyran-based small molecules was constructed by Nicolaou and coworkers [74, 75]. They chose a solid-phase approach and an anchoring strategy that does not limit complexity building operations (Scheme 14.11). They used a polystyrene-based selenyl bromide resin (43) on which substrates can be immobilized by electrophilic cyclization reactions. Here, ortho-prenylated phenol 44 was reacted with the selenyl bromide (43) to form the benzopyran scaffold (45) via a 6-endo-trig cyclization. 

Scheme 14.12 Diversification of the benzopyran scaffold on solid support.

Breitenbucher and Hui (104) have recently reported the SP synthesis of a medium-large discrete library L3 of 8448 benzopyrans using the reductive amination cocktail formed from titanium isopropoxide and sodium triacetoxyborohydride, known in solution but whose applications to SP were rare and limited to single experiments (105, 106). The benzopyran scaffold is present in a number of biologically active compounds (107-110), and this library was tested in several biological assays (111). 

Scheme 13 Accessible Benzopyran Scaffolds on solid phase...

The directed sorting approach has been widely applied both in industry and in academia. Two examples are detailed in this chapter. Some other recently published examples include a benzopyran library synthesized using the Nanokan system,15 libraries derived from phenolic amino acid scaffolds prepared with the Accutag system,16 and libraries of l,5-benzodiazepine-2-one derivatives.17... 

Song, A. M. Zhang, J. H. Lam, K. S. Synthesis and reaction of 7-fluoro-4-methyl-6-nitro-2-oxo- 2H l-benzopyran-3-carboxylic acid A novel scaffold for combinatorial synthesis of coumarins. J. Com. Chem., 2004, 6(1) 112-120. 

FIGURE 11.83 Solid-phase synthesis of psoralen analogs. (From Song, A., Zhang, J., and Lam, K.S., Synthesis and reactions of 7-fluoro-4-methyl-6-nitro-2-oxo-27f-l-benzopyran-3-carboxylic acid a novel scaffold for combinatorial synthesis of coumarins, J. Comb. Chem., 6,112, 2004 Song, A. et al.. Solid-phase synthesis and spectral properties of 2-alkylthio-6//-pyrano[2,3-/ benzimidazole-6-ones a combinatorial approach for 2-aUcylthioimidazo coumarins, J. Comb. Chem., 6, 604, 2004 Song, A. and Lam, K.S., Parallel sohd-phase synthesis of 2-arylamino-6H-pyrano [2,3-f] benzimidazole-6-ones, Tetrahedron, 60, 8605, 2004.)... 

---