Dihydropyrimidone acid

Several compounds derived from these libraries were identified as Hsp70 modulators and were further evaluated in cell proliferation assays such as the SK-BR-3 and MCF-7 breast cancer cell lines and the HT29 colon cancer cell line (Fig. 6) [26]. Compounds 22-24 were potent against all three cell lines. The dihydro-pyrimidinone libraries were also tested for replication inhibition of the malarial parasite, Plasmodium falciparum, where Hsp70 chaperones are believed to play an important role in the parasite s homeostasis [24]. Nine compounds that inhibit replication of the parasite were identified. Among them, compounds 25 and 26 were the most potent (Fig. 7) and were prepared by direct couplings of dihydropyrimidone acids 19 with a pyrrolo amine. 

A side effect of a lack of temperature control is that changes can alter the refractive index of the mobile phase, causing basehne disturbances and reducing sensitivity The problem is principally with refractive index detection [39], but it can also influence spectroscopic detectors and their light path can be distorted. Temperature has also been reported to alter the nature of some stationary phases. For example, it caused a change in the chiral selectivity of the resolution of dihydropyrimidone acid and its methyl ester on amylose and cellulose stationary phases [40],... 

F. Wang,T. 0 Brien,T. Dowling, G. Bicker, and J. Wyvratt, Unusual effect of column temperature on chromatographic enantioseparation of dihydropyrimidone acid and methyl ester in amylose chiral stationary phase, J. Chromatogr. A 958 (2002), 69-77. 

Dondoni and Massi9 executed a Bignelli synthesis to prepare dihydro-pyrimidinones starting from aldehydes, 1,3-dicarbonyl compounds, and urea with ytterbium(III) supported on Amberlyst 15 resin as a Lewis acid (entry 5). After condensation, the reaction mixture is treated with both strongly basic and acid resins to sequester reaction by-products. For more than 30 reported examples, dihydropyrimidones obtained directly from concentration of the filtrates are produced in high yields and in excellent purities. 

This acid-catalyzed, three-component reaction between an aldehyde, a i-ketoester and urea constitutes a rapid and facile synthesis of dihydropyrimidones, which are interesting compounds with a potential for pharmaceutical application. 

Chromatography of the electrolysis products formed in acid medium demonstrated that the major one was the photodissociable dimer 6,6 -6w-(3,6-dihydropyrimidone-2) (70%), accompanied by 3,6-dihydropyrimidone-2 (15 %) and about 15 % of a product not fully identified, but the UV absorption spectrum of which was consistent with its being a 1 1 adduct of cytosine and reduced pyrimidone-2 84). 

In acid medium (pH 4.5) electrochemical reduction led to formation of two products. One of these was characterized as the 6,6 -dimer of the riboside of pyrimidone-2. It was photochemically converted to the riboside of pyrimidone-2. The second, on the basis of its chromatographic behaviour, UV spectrum, and reaction with the Fink reagent, was identified as the riboside of 3,6-dihydropyrimidone-2. The mechanism of electrochemical reduction of cytidine in acid medium is consequently analogous to that for 1-methylcytosine. The products of reduction of cytidine at pH 7 were shown chromatographically to contain 5,6-dihydrocytidine 1 84). A comparison of the electrochemical and catalytic reduction products under analogous conditions at pH 7 demonstrated that both led to the same products, one of them 5,6-dihydrocytidine 84). 

Related Reactions. The photochemistry (Patemo-Biichi reactions) of the achiral oxazoline (7) has been studied. The analogous urethane (8), which is chiral by attachment of an apocam-phanoyl group, shows an intriguing stereoselectivity pattern in its reaction with electrophiles. For another case of an oxidative decarboxylation as a key step in the application of the SRSC (selfregeneration of stereogenic centers) principle, see the preparation of the dihydropyrimidone (9) from aspartic acid. ... 

Soon after, the groups of Ricci [35] and Schaus [36] also employed a-amidosulfones as stable imine precursors in cinchona-catalyzed Mannich reactions. Ricci and coworkers reported [35] that, under PTC conditions (toluene/aqueous K2C03) using 75 as a catalyst (1 mol%), both the aliphatic and aromatic a-amido p-tolylsulfones 76 reacted with the malonates to afford the Mannich adducts 77 with high levels of enantioselectivity (85-99% ee) (Scheme 8.25). The subsequent decarboxylation/ transesterification of 77 gave the corresponding [3-amino acid derivatives without any alternation of the optical purities. The chiral dihydropyrimidones 80 were also successfully synthesized by Schaus and coworkers via the cinchonine catalyzed... 

Rafiee, E., Shahbazi, F. 2006. One-pot synthesis of dihydropyrimidones using silica-supported heteropoly acid as an efficient and reusable catalyst Improved protocol conditions for the Biginelli reaction. Journal of Molecular Catalysis A Chemical 250(l-2) 57-61. 

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