Michael broad spectrum

In 2007, Chen and co-workers reported the 122-catalyzed (10mol% loading) enantioselective Michael addition [149-152] of ethyl a-cyanoacetate to various electron-rich and electron-deficient trans-chalcones [283]. The reaction was performed for a broad spectrum of chalcones and gave the corresponding adducts in yields of 80-95% and in ee values of 83-95%, but at low sy /a ti-diastereoselectiv-ities as shown for representative products 1-8 in Scheme 6.125. 

The Michael reactions [149-152] between cyclohexanone and trons-nitroalkenes were also explored by Xiao and co-workers utilizing bifunctional pyrrolidine-thiourea 213 and the pyrrolidine-thioureas 214-217 (Figure 6.61) [344]. The model Michael reaction between cyclohexanone and trons-nitrostyrene identified water as the best solvent and 217 to be the most efficient catalysts concerning the activity and asymmetric induction (90% yield 96% ee dr 98 2 in 12 h at 35 °C) in the presence of benzoic acid (10mol%) as additive. The optimized catalytic system allowed the formation of a broad spectrum of Michael adducts such as 1-6 resulting from... 

Soon afterward, a broad spectrum of Michael donors and Michael acceptors were successfully employed in the thiourea-catalyzed Michael addition [24—27]. Selected examples are outlined in Schemes 9.31-9.33. 

In 2006, Wang and coworkers reported the asymmetric Michael addition of a broad spectrum of nucleophiles to chalcones (25) using the thiourea catalyst 81a [24],... 

Another nucleoside-derived mechanism-based enzyme inhibitor is Fluoronepla-nocin A [79]. This compound is of interest as a broad-spectrum antiviral drug which acts by irreversible inhibition of S-adenosylhomocystein hydrolase (SAH). In a first enzymatic reaction step the 3 -hydroxy group of the inhibitor is oxidized to the corresponding ketone (Scheme 4.34). This leads to depletion of the biochemical oxidizer nicotinamide adenine dinudeotide (NAD ). In the next step a nucleophilic residue of the enzyme undergoes Michael addition to the /i-fluoro a,/>-unsatu-rated ketone moiety. This is followed by fluoride elimination and thus the inhibitor stays covalently trapped in the active site and disables the enzyme permanently. 

Pyrazole and its 3,5-dimethyl and 3,4,5-trimethyl derivatives combined with two moles of dimethyl acetylenedicarboxylate giving products of similar ultraviolet absorption spectra to the parent pyrazoles. These products [e.g., (69)] do not possess the strong broad absorption at ca. 3.20 /u, characteristic of the bonded N—H group which is present in the parent pyrazoles and are formed by two successive Michael addition reactions. In the case of 3,5-dimethylpyra-zole, the initial fumarate (68) has been isolated and possessed a more conjugated type of absorption spectrum to those of the dipyrazolyl-... 

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