Quinone methide property

MODELING PROPERTIES AND REACTIVITY OF QUINONE METHIDES BY DFT CALCULATIONS... 

Quinone methide complexes were characterized by standard spectroscopic techniques. It is possible to elucidate the structural and electronic properties of the QM complexes and also to estimate the reactivity tendencies of the coordinated QM moiety based on IR, NMR, and X-ray diffraction spectroscopes. 

To assess the trapping of biological nucleophiles, the pyrido[l,2-a]indole cyclopropyl quinone methide was generated in the presence of 5 -dGMP. The reaction afforded a mixture of phosphate adducts that could not be separated by reverse-phase chromatography (Fig. 7.16). The 13C-NMR spectrum of the purified mixture shown in Fig. 7.16 reveals that the pyrido [1,2-a] indole was the major product with trace amounts of azepino[l,2-a] indole present. Since the stereoelec-tronic effect favors either product, steric effects must dictate nucleophilic attack at the least hindered cyclopropane carbon to afford the pyrido[l,2-a]indole product. Both adducts were stable with elimination and aromatization not observed. In fact, the pyrido [1,2-a] indole precursor (structure shown in Scheme 7.14) to the pyrido [l,2-a]indole cyclopropyl quinone methide possesses cytotoxic and cytostatic properties not observed with the pyrrolo [1,2-a] indole precursor.47... 

Table 7.3 shows the concentrations of 1-5 that result in 50% growth inhibition (GI50) of five human cancer cell lines. Inspection of these data reveals that cytostatic activity of 1 and 3-5 depends on the thermodynamic favorability of the quinone methide species compared to the corresponding keto form. The most cytostatic prekinamycins 1 and 5 are associated with the thermodynamically stable quinone methides. In contrast, the inactive prekinamycins 3 and 4 are associated with thermodynamically stable keto tautomers. The exception is prekinamycin 2, which is cytostatic and possesses a relatively stable keto tautomer 3 compared to its quinone methide. Although the AE value for quinone methide tautomerization can predict cytostatic properties, prekinamycin 2 shows that there must be other factors determining biological activity. 

KhdourO. SkiboE. B. Chemistry of pyrrolo[l,2-a]indole- andpyrido[l,2-a]indole-based quinone methides. Mechanistic explanations for differences in cytostatic/cytotoxic properties. J. Org. Chem. 2007, 72, 8636-8647. 

One interesting property of quinone methide 63 is that the terminal carbon of the extended conjugated system lies in both an extended quinone methide (carbons marked by +) and an extended enol (carbons marked by ). This carbon reacts as both a base in undergoing protonation to form a quinone (upper pathway, Scheme 30A) and a Lewis acid in undergoing addition of nucleophilic... 

The photochromic properties of 2/7-chromene derivatives has generated much interest in recent years. Under UV irradiation these molecules can undergo reversible electrocyclic opening of the pyran ring to afford colored ortho-quinone methides <2005T11730, 2005T1681>. 

The structures and properties of quinone methides were recently reviewed . Inter alia, the microbial tyrosine phenol lyase (TPL) catalyzes the a, /3-elimination of L-tyrosine to phenol and ammonium pyruvate. It is assumed that the process includes three steps, the second of which is tautomerization of the aromatic moiety which converts it into a good leaving group (equation 49) °. 

A particular feature of the high-temperature-crosslinked resin is the darkening due to the formation of quinone methide (Scheme 1.14). Since this reaction is important only above 160 C, by using acid catalysts at r< 80 °C darkening can be avoided. In principle the acid-catalysed reaction will occur at room temperature, but for the best properties a post-cure reaction up to 80 C is required. 

The enzyme vanillyl-alcohol oxidase (VAO, E.C. 1.1.3.38) was examined in detail with respect to mechanism, structural properties, and biotechnological applications by van Berkel and coworkers, giving an excellent example of how detailed biochemical studies provide a basis for preparative biocatalytic applications (for recent reviews see[1, 21). The homooctamer with a monomer mass of 65 kDa was isolated and purified from Penicillium simplicissimum. The catalytic mechanism of VAO-catalyzed oxidation of para-alkyl phenols was studied in detail[3-5 After initial hydride abstraction from the Ca atom, a binary complex of the intermediate para-quinone methide and reduced FAD reacts with molecular oxygen, regenerating the... 

The predominant feature of the flavan-3,4-diols as far as the chemistry of the proanthocyanidins is concerned is their role as precursors to flavan-4-yl carhocations and/or A-ring quinone methide electrophiles. As such they represent the extension units of the polymeric chain of the naturally occurring proanthocyanidins. The physico-chemical properties regulating their role and function in the synthesis of the proanthocyanidins were extensively covered in CONAP-I. ... 

Studies of the generation and properties of o-quinone methide imines38-42 (Table 9-III) suggest that with continued investigation they will prove to be useful synthetic intermediates comparable to the o-xylylenes43 and o-quinone methides.44 Although a few notable examples of successful efforts to trap the unstable o-quinone methide imines in intermolecular [4 +... 

---