Benzopyranones synthesis

Benzopyranone synthesis from phenols and 3-ketoesters or unsaturated acids (see 1st edition). 

Benzo[g]pteridine, 2,4-diaminotetrahydro-synthesis, 3, 317 Benzopurines, 5, 567 Benzopyranones... 

In the realm of natural product synthesis, Kepler and Rehder utilized the K-R reaction to synthesize ( )-calanolide A (56), a potent non-nucleosidal human irmnunodeficiency virus (HIV-1) specific reverse transcriptase inhibitor. Propiophenone 57 was allowed to react with acetic anhydride in the presence of sodium acetate to afford benzopyranone 58 in 56% yield subsequent deacetylation of 58 gave 59. Flavone 59 was then transformed to ( ) calanolide A (56) over several steps. 

G. C. Selective benzopyranone and pyrimido[2,l-a]isoquinolin-4-one inhibitors of DNA-dependent protein kinase synthesis, structure-activity studies, and radiosensitization of a... 

Two disadvantages are associated with this synthesis. Yields range from low to moderate and, of more significance, cyclization of the initially formed ester can give rise to chromones or coumarins or to mixtures of the two heterocycles. With the wide range of analytical techniques now available, it is not difficult to distinguish the isomeric benzopyranones. However, some of the structural assignments in early work have been shown to be erroneous and care is therefore advised in the interpretation of results. 

The design of the library L3 and the synthetic scheme are reported in Fig. 6.15 filtration of the solutions and washing of the resin aliquots were performed after each step. The three supported benzopyranones 6.32 (step a, from the monomer set Mi, three ketones) were obtained in a similar manner to 6.29 on a 300-g scale. Each resin-supported benzopyranone was split into 8 separate peptide synthesis flasks containing 35 g of resin and all of the 24 samples were reductively aminated (steps b and c, monomer set M2, eight amines) to produce 24 resin-bound intermediates 6.33. Each intermediate was then divided into 352 portions of 100 mg of resin that were distributed into four filter-bottom 96-well microtiter plates (2.0 mL capacity per well). 

Linker 88 has been successfully employed in the synthesis of a small hbrary of benzopyranones, of which the individual compounds were obtained in high yields and purities [101]. A further application of the linker has been in the synthesis of oligo(3-aryl-thiophenes) [102]. 

The synthesis of a series of triazolobenzopyranones carrying piperazinoalkoxy substituents on the phenyl ring demonstrated the feasibility of integrating the mast-cell-stabilizing properties of the chromone (benzopyranone) moiety and H( antihistaminic properties into one molecule. The most effective compound of a small series was BR-28390. Its antihistaminic potency (guinea pig ileum) was the same as mepyramine histamine release inhibition effectiveness (tested by rat passive peritoneal anaphylaxis) was somewhat less than cromolyn. 

Besides the synthesis of various triazoles, the synthetic potential of the copper flow system was further demonstrated by the catalytic decarboxylation of the propargyhc add 11 (Scheme 4, Reaction 2) and the C—O coupling in the synthesis of benzopyranone 14 (Scheme 4, Reaction 3) (2010SL2009). 

The ortho-arylation reaction of phenolates with aryldiazonium sulfides as radical precursors represents an efficient process for the synthesis of benzopyranones and related compounds (Equation 13.4). The intermediately formed SrnI products are readily transformed in situ to the corresponding benzopyranones under mild acidic reaction conditions [15]. 

Studies in the laboratory of Tanaka toward the synthesis of bikaverin 20, a fungal metabolite with a benzo-xanthen skeleton, led to the discovery of an elegant method to form ring C. Upon treatment with aqueous oxalic acid, benzopyranone 16 was directly transformed into xanthone 17, which could be potentially elaborated intro bikaverin 20. The unexpected formation of intermediate 17 could be explained by the following sequence hydrolysis... 

Upon careful examination of reaction parameters, Tanaka and coworkers successfully developed a highly enantioselective lactone synthesis by reaction with both aldehydes and activated ketones as the coupling partners for the synthesis of spirocyclic benzopyranones. Cationic Rh catalysts were again found to be the most efficient. Importantly, homodimerization of the parent 2-aIkynylbenzaldehydes was not observed under the optimized conditions [92]. 

Scheme 3.9 Palladium-catal ed carbonylative synthesis of benzopyranones. (a)...

This year has seen the publication of the first convenient synthesis of crotonophenones, which are open chain forms of benzopyranones (chromanones). Previous attempts at their synthesis via Friedel-Crafts or simple aldol reactions gave poor yields. However, it has now been shown that the dianion of n-hydroxyacetophenones will react with aldehydes, and dehydration of the products constitutes a simple synthesis of crotonophenones and also of 2-methyl chromanones. 

N. Thasana, R. Worayuthakarn, P. Kradanrat, E. Hohn, L. Yormg, S. Ruchirawat, Copper(I)-mediated and microwave-assisted Caiyi-Ocarbo uc coupling synthesis of benzopyranones and isolamellarin alkaloids, J. Org. Chem. 72 (2007) 9379-9382. 

It is interesting to note that addition of NaH to Zn reducing agent in toluene facilitates the reductive coupling reaction of benzopyranone derivatives. Under these conditions, side products (e.g. reduction of C-I bond) can be suppressed. This reaction has been used for the synthesis of bisbenzopyran-4-ol [17]. 

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