3-Formylchromone

Imino derivatives 61 were obtained directly from 3-formylchromone [36] 59 and creatinine [37] 60, with DM SO as solvent and boric acid as catalyst, and with micro-wave irradiation and classical heating (Tab. 8.4). The authors have also investigated the preparation of the 2-thioxo-5-imidazolidin-4-ones 63 from thiohydantoin 62 in... 

Chromone-3-carbonitrile oxide obtained from 3-formylchromone oxime by bromination and subsequent dehydrobromination underwent cycloaddition reactions with terminal alkenes to give isoxazolines 34 (175). 

Treatment of 3-formylchromone (95) and 4-amino-3-phenyl-5-triazolinethione (96) with KOH and TBAHSO4 in benzene also gave a bicyclic derivative (97) (Equation (34)) <87SC1851>. 4-Amino-3-triazolinethione (98) reacts with the diketoacetylene (99) in a similar manner to give (100) (Equation (35)) <92CHE222>. 

Diels-Alder reactions have featured heavily during the period of review. Ar-Vinyl-2-oxazolidinone has been reported as a dienophile for the first time, including the preparation of various tetrahydro-277,77/-pyrano[4,3-. ]pyrans <2002SL952>. The heterodiene cycloaddition reaction of 3-formylchromone with a series of ketene acetals formed from C2-symmetric l,2-diarylethane-l,2-diols is completely diastereoselective (Scheme 40) <1995J(P1)2293>. 

The cycloaddition of ketene acetals to 3-formylchromone exhibits good diastereoselectivity and meihanolysis of the pyrano[4,3- ] -pyran affords the chromanone ester (21) without racemisation. The chiral auxiliary, the diol (22), can be recyclised and the overall process represents an asymmetric conjugate addition to the chromone (95 JCS(P1 )2293). 

Benzopyrylium triflates formed in situ from 3-formylchromones react in a sequential fashion with silyl enol ethers to give chromones such as 111 (Scheme 7) <2003TL7921, 2006T7674, 2002CC168, 2006CEJ1221, 2006T9694, 2006EJO3638>. 

The reactivity of 47/-benzopyran-4-ones in Diels-Alder reactions is well documented <1987T3075>, and recently high asymmetric induction has been achieved in the reaction of 3-alkoxycarbonyl-substituted chromones with chiral auxiliaries and Danishefsky s diene <1991JOC2058>. It should be noted that 3-formylchromones can react as heterodienes in the stereoselective inverse electron Diels-Alder reaction with enol ethers <1994T11755> to provide a route to pyrano[4,3-A][l]benzopyrans a heterocyclic nucleus which occurs naturally in the fungal metabolite fulvic acid <1984CC1565>. The thermal Diels-Alder reaction of 477-pyran-4-one 405 in the presence of an excess of Danishefsky s diene 404 provided cycloadduct 406 (Equation 32) <1996H(43)745>. 

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]. 

The 6-substituted 3-formylchromone derivatives (FC1-8) screened for their tumor-specific cytotoxic potentials are shown in Fig. 7. Their CC50 values for the four tumor cell fines and three normal cells are summarized in Table 3. Cytotoxic data for the related chromone derivatives (FC9-13),... 

Fig. 7 Chemical structures and calculated logP values of 3-formylchromone and coumarin derivatives (FC1-16)...

Table 3 Cytotoxic activity of 3-formylchromones and related compounds against tumor and normal cells...

The results show that all the 6-substituted 3-formylchromones, and the 6-nitro-substituted derivative FC5, exhibit a more potent cytotoxicity against tumor cell lines than the parent 3-formylchromone (FC1). However, there was no clear-cut correlation between the chemical structure of the com-... 

Margita, L., Agnieszka, P, Solcanyova, E., Lac, J., Kois, P, Chovancova, J., and Danuta, R. 2005. 3-Formylchromones IV. The rearrangement of 3-formylchromone enamines as a simple, facile route to novel pyrazolo[3,4-b]pyridines and the synthetic utility of the Isittet. Molecules, 10 809-821. 

Sabitha, G. 1996. 3-Formylchromone as a versatile synthon in heterocyclic chemistry. Aldrichimica Acta, 29 15-25. 

Stankovicova, H., Fabian, W. M. F., Lacova, M. Synthesis and theoretical study of Mannich type reaction products of 3-formylchromones with triazoles and amides and nucleophilic formation of 2,3-disubstituted-4-chromanones. Molecules [Electronic Publication] 1996,1, 223-235. 

Fig. 13 Structures of 3-formylchromone derivatives used in this study...

Fig. 14 The most stable conformation of each 3-formylchromone derivative used...

Table 7 CC50 and chemical descriptors for 3-formylchromone derivatives...

Fig. 15 Relationship between CC50 and each chemical descriptor of 3-formylchromone derivatives against HSG (A-1 to A-8) and HL-60 cells (B-1 to B-5)...

In conclusion, there was the best relationship between CC50 and descriptors in HSG cells. This cell line may provide the opportunity to search more active 3-formylchromone derivatives using QSAR with the concept of absolute hardness. 

The third chapter, Quantitative Structure-Cytotoxicity Relationship of Bioactive Heterocycles by the Semi-empirical Molecular Orbital Method with the Concept of Absolute Hardness by Mariko Ishihara, Hiroshi Sakagami, Masami Kawase, and Noboru Motohashi, presents the relationship between the cytotoxicity (defined as 50% cytotoxic concentration) of heterocycles such as phenoxazine, 5-trifluoromethyloxazoles, O-heterocycles such as 3-formylchromone and coumarins, and vitamin K2 derivatives against some tumor cell lines and 15 chemical descriptors. The results suggest the importance of selecting the most appropriate descriptors for each cell type and compound. The review is of interest as it represents the relationship of the molecular structures with the cytotoxic activity of these heterocycles. 

In the presence of the newly developed chiral organocatalyst le, the ring annu-lation reaction of acetylene dicarboxylates and 3-formylchromones successfully gave rise to tricyclic benzopyrones 7 in good yield (46-91%) and with enantioselectivity of 81-87% ee (Table 10.4) [14],... 

Reactions with diethyl(ethoxymethylene)malonate or 3-formylchromone gave pyrimidine... 

---